bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy
Authors: Tang Xing-hua , Wu Xun-yi , Xu Lan , Fang You-xin , Wang Jian-hong , Zhu Guo-xing , Hong Zhen
Published: January 2024

Background

Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE).

Methods

Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death.

Results

There were 46.88±10.70 survival neurons in tenidap-SE group, while there were 27.60±5.18 survival neurons in saline-SE group at −2.4 mm field in the CA3 area. There were 37.75±8.78 survival neurons in tenidap-SE group, while there were 33.40±8.14 survival neurons in saline-SE group at −2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P <0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area.

Conclusion

Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.
Clinicopathology, immunophenotype, T cell receptor gene rearrangement, Epstein-Barr virus status and p53 gene mutation of cutaneous extranodal NK/T-cell lymphoma, nasal-type
Authors: WANG Ting-ting , XU Chen , LIU Shan-ling , KAN Bei , RAN Yu-ping , LIU Wei-ping , LI Gan-di , WANG Lin
Published: January 2024

Background

Extranodal natural killer/T-cell (NK/T cell) lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to investigate the clinicopathologic features, immunophenotype, T cell receptor (TCR) gene rearrangement, the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.

Methods

The clinicopathologic analysis, immunohistochemistry, in situ hybridization for EBER1/2, TCR gene rearrangement by polymerase chain reaction (PCR), mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.

Results

In the 19 cases, the tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical staining showed that most of the cases expressed CD45RO, CD56, CD3e, TIA-1 and GrB. Three cases were positive for CD3 and two cases were positive for CD30. Monoclonal TCRγ gene rearrangement was found in 7 of 18 cases. The positive rate of EBER1/2 was 100%. No p53 gene mutation was detected on the exon 4-9 in the 18 cases. Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72. The expression of p53 protein was 72% (13/18) immunohistochemically.

Conclusions

Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was detected on the exon 4-9, and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the result of p53 gene mutation.
Protective effects of astragalus extract against intermittent hypoxia-induced hippocampal neurons impairment in rats
Authors: ZHANG Qiang , GAO Wen-yuan , ZHANG Yun , CHEN Bao-yun , CHEN Zhe , ZHANG Wei-san , MAN Shu-li
Published: January 2024

Background

Intermittent hypoxia is the main pathophysiological cause of the obstructive sleep apnea syndrome. Astragalus shows improvement of spatial learning and memory abilities under intermittent hypoxia. Our study aimed to investigate the protective effect of astragalus against intermittent hypoxia induced-hippocampal neurons impairment in rats and lay the theoretical foundation for the sleep apnea improvement in cognitive function by astragalus.

Methods

Male Wistar rats were divided into 4 groups: blank control group, normoxia group, intermittent hypoxia group and astragalus treated intermittent hypoxia group. After 6-week treatment, apoptosis of neurons was evaluated by terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) assay. Furthermore, the expression of HIF-1a was detected by real-time reverse transcription polymerase chain reaction (RT-PCR) at the mRNA level as well as by immunohistochemistry (IHC) and Western blotting at the protein level.

Results

HPLC analysis indicated that astragaloside IV, astragaloside II and astragaloside I were the main compounds in astragals extract. Astragalus extract reduced the apoptosis of hippocampal neurons (P <0.05) and decreased the expression of HIF-1a at both the mRNA and protein levels in hippocampus compared with non-treated groups (P <0.05).

Conclusion

Astragalus protects against intermittent hypoxia-induced hippocampal neurons impairment in rats.
Telithromycin versus clarithromycin for the treatment of community-acquired respiratory tract infections: a meta-analysis of randomized controlled trials
Authors: LI Xiu-min , WANG Feng-chun , YANG Feng , JIN Ying-hua
Published: January 2024

Background

The emergence of bacterial resistance to commonly used antibiotics, such as macrolides, is complicating the management of respiratory tract infections (RTIs). Telithromycin, a ketolide antimicrobial structurally related to macrolides, is approved for the treatment of community-acquired RTIs, and shows lower pathogen resistance rates. The purpose of this study was to compare the efficacy and safety of telithromycin with clarithromycin, a macrolide routinely used as therapy for RTIs.

Methods

We performed a meta-analysis of relevant randomized-controlled trials (RCTs) identified in PubMed, the Cochrane Library, Embase, CNKI and VIP databases. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure time in the per-protocol population, and the primary safety outcome was drug related adverse effects.

Results

Seven RCTs, involving 2845 patients with RTIs, were included in the meta-analysis. Oral telithromycin and clarithromycin showed a similar clinical treatment success in modified intention to treat and per-protocol population (cure and improvement) (odds ratios (ORs): 0.84, 95% confidence intervals (CI): 0.64-1.11 and OR: 1.14, 95% CI: 0.71-1.85, respectively). Similar findings were obtained for secondary efficacy outcomes: clinical treatment success at a late post-therapy visit (OR: 0.92, 95% CI: 0.57-1.48) and microbiological treatment success at the test-of-cure time (OR: 1.14; 95% CI: 0.71-1.85). The safety outcome analysis indicated telithromycin had a similar risk of drug-related adverse effect and serious adverse effect with clarithromycin.

Conclusions

Our findings indicate that oral telithromycin and clarithromycin have similar treatment efficacy and adverse effect. The advantages of lower antimicrobial resistance rates, once-daily short-duration dosing and reported lower healthcare costs make oral telithromycin a useful option for the empiric management of mild-to-moderate RTIs.
Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation
Authors: MO Xiao-dong , XU Lan-ping , LIU Dai-hong , ZHANG Xiao-hui , CHEN Huan , CHEN Yu-hong , HAN Wei , WANG Yu , WANG Feng-rong , WANG Jing-zhi , LIU Kai-yan , HUANG Xiao-jun
Published: January 2024

Background

The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT.

Methods

A nested case-control study was designed. Cases with BOS and controls matched for the year of allo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent allo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia.

Results

Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7±12.4) years, and the mean time to presentation was (474±350) days post-HSCT. A pre-HSCT cyclophosphamide dose of ≥3.2 g/m2 (OR=8.74, P=0.025), chronic graft-versus-host disease (moderate to severe) (OR=12.02, P=0.000), and conditioning regimens without antithymocyte globulin (OR=2.79, P=0.031) were independently associated with BOS.

Conclusions

We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after allo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.
Chronic intermittent hypoxia increases β cell mass and activates the mammalian target of rapamycin/hypoxia inducible factor 1/vascular endothelial growth factor A pathway in mice pancreatic islet
Authors: GU Chen-juan , LI Min , LI Qing-yun , LI Ning
Published: January 2024

Background

Growing evidence from population and clinic based studies showed that obstructive sleep apnea (OSA) and its characterizing chronic intermittent hypoxia (IH) were independently associated with the development of type 2 diabetes mellitus. However, the pathogenesis by which OSA induces glucose metabolic disorders is not clear. We determined changes in pancreatic β cell mass and the mammalian target of rapamycin (mTOR)/hypoxia inducible factor 1 (HIF-1)/vascular endothelial growth factor A (VEGF-A) pathway following IH exposure.

Methods

A controlled gas delivery system regulated the flow of nitrogen and oxygen into a customized cage housing mice during the experiment. Twenty-four male wild C57BL/6J mice were either exposed to IH (n=12) or intermittent air as a control (n=12) for 56 days. Mice were anaesthetized and sacrificed after exposure, pancreas samples were dissected for immunofluorescent staining. Insulin and DAPI staining labelled islet β cells. Insulin positive area and β cell number per islet were measured. P-S6, HIF-1α and VEGF-A staining were performed to detect the activation of mTOR/HIF-1/VEGF-A pathway.

Results

After eight weeks of IH exposure, insulin positive area increased by an average of 18.5% (P <0.05). The β cell number per islet increased (92 vs. 55, respectively for IH and the control groups, P <0.05) with no change in the size of individual β cells. Islet expression of HIF-1α and VEGF-A were higher in IH group than control group, and percentage of p-S6 positive β cell also increased after IH exposure (16.8% vs. 4.6% respectively for IH and the control groups, P <0.05).

Conclusion

The number of pancreatic β cells increased as did the activity of the mTOR/HIF-1/VEGF-A pathway after exposure to IH.
Efficacy and safety of the treatment: combination of benazepril/lercanidipine vs. benazepril alone in patients with mild-to-moderate hypertension
Authors: CHEN Ting , CHEN Guang-hui , YANG Ting-shu , ZHONG Zhen-yu , AN Wei-shuai , ZHANG Xiao-xia , LI Jia-dan
Published: January 2024

Background

Combination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension.

Methods

One hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks.

Results

The baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P <0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P <0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P >0.05), 67.1% vs. 44.7% (P <0.05), and 71.8% vs. 45.9% (P <0.05). There was no significant difference of side effects between the two groups.

Conclusion

The benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.
Bioactive proteins in healthy pregnancies and preeclampsia: relevance to hypertension and proteinuria
Authors: WANG Tao , WANG Yan-yun , ZHOU Rong , SONG Chang-ping , LIN Wei , NIU Xiao-yu , ZHANG Lin , HU Huai-zhong
Published: January 2024

Background

Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia.

Methods

Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay.

Results

Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preeclampsia patients. In particular, interleukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients.

Conclusions

Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.
High risk factors of brain metastases in 295 patients with advanced breast cancer
Authors: YAN Min , LÜ Hui-min , LIU Zhen-zhen , LIU Hui , ZHANG Meng-wei , SUN Xi-bin , CUI Shu-de
Published: January 2024

Background

The incidence of brain metastases in patients with breast cancer is approximately 10%—16%, and survival after diagnosis of brain metastases is usually short. This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients, with a view to help predict patient groups with high risk of brain metastases.

Methods

In total, 295 patients with advanced breast cancer were evaluated. All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging. All patients were examined at least once every 6 months with head CT or MRI. Patients showing symptoms underwent immediate inspection, and brain metastatic lesions were confirmed by head CT and/or MRI.

Results

At a median follow-up of 12 months from the occurrence of metastases, brain metastases had occurred in 49 patients (16.6%). In our univariate analysis, variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors, epidermal growth factor receptor 2 (HER2)-positive tumors, and multiple distant metastases. Patients with dominant tumor sites in soft tissue, or defined as Luminal A subtype, tended to have a lower risk of brain metastases than patients with visceral metastases, Luminal B subtype, triple-negative subtype or HER2-enriched subtype tumors.

Conclusions

Our results strongly suggest that factors such as Luminal B, triple-negative, and HER2-enriched subtypes are high risk factors for brain metastases. These data, therefore, provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.
Anatomical study of endoscope-assisted far lateral keyhole approach to the ventral craniocervical region with neuronavigational guidance
Authors: GUAN Min-wu , WANG Jia-yin , FENG Dong-xia , FU Paul , CHEN Li-hua , LI Ming-chu , ZHANG Qiu-hang , SAMII Amir , SAMII Madjid , KONG Feng , ZHANG Zhi-ping , CHEN Ling
Published: January 2024

Background

Image-guided neurosurgery, endoscopic-assisted neurosurgery and the keyhole approach are three important parts of minimally invasive neurosurgery and have played a significant role in treating skull base lesions. This study aimed to investigate the potential usefulness of coupling of the endoscope with the far lateral keyhole approach and image guidance at the ventral craniocervical junction in a cadaver model.

Methods

We simulated far lateral keyhole approach bilaterally in five cadaveric head specimens (10 cranial hemispheres). Computed tomography-based image guidance was used for intraoperative navigation and for quantitative measurements. Skull base structures were observed using both an operating microscope and a rigid endoscope. The jugular tubercle and one-third of the occipital condyle were then drilled, and all specimens were observed under the microscope again. We measured and compared the exposure of the petroclivus area provided by the endoscope and by the operating microscope. Statistical analysis was performed by analysis of variance followed by the Student-Newman-Keuls test.

Results

With endoscope assistance and image guidance, it was possible to observe the deep ventral craniocervical junction structures through three nerve gaps (among facial-acoustical nerves and the lower cranial nerves) and structures normally obstructed by the jugular tubercle and occipital condyle in the far lateral keyhole approach. The surgical area exposed in the petroclival region was significantly improved using the 0° endoscope (1147.80 mm2) compared with the operating microscope ((756.28±50.73) mm2). The far lateral retrocondylar keyhole approach, using both 0° and 30° endoscopes, provided an exposure area ((1147.80±159.57) mm2 and (1409.94±155.18) mm2, respectively) greater than that of the far lateral transcondylar transtubercular keyhole approach ((1066.26±165.06) mm2) (P <0.05).

Conclusions

With the aid of the endoscope and image guidance, it is possible to approach the ventral craniocervical junction with the far lateral keyhole approach. The use of an angled-lens endoscope can significantly improve the exposure of the petroclival region without drilling the jugular tubercle and occipital condyle.
New insight into genes in association with asthma: literature-based mining and network centrality analysis
Authors: LIANG Rui , WANG Lei , WANG Gang
Published: January 2024

Background

Asthma is a heterogeneous disease for which a strong genetic basis has been firmly established. Until now no studies have been undertaken to systemically explore the network of asthma-related genes using an internally developed literature-based discovery approach. This study was to explore asthma-related genes by using literature-based mining and network centrality analysis.

Methods

Literature involving asthma-related genes were searched in PubMed from 2001 to 2011. Integration of natural language processing with network centrality analysis was used to identify asthma susceptibility genes and their interaction network. Asthma susceptibility genes were classified into three functional groups by gene ontology (GO) analysis and the key genes were confirmed by establishing asthma-related networks and pathways.

Results

Three hundred and twenty-six genes related with asthma such as IGHE (IgE), interleukin (IL)-4, 5, 6, 10, 13, 17A, and tumor necrosis factor (TNF)-alpha were identified. GO analysis indicated some biological processes (developmental processes, signal transduction, death, etc.), cellular components (non-structural extracellular, plasma membrane and extracellular matrix), and molecular functions (signal transduction activity) that were involved in asthma. Furthermore, 22 asthma-related pathways such as the Toll-like receptor signaling pathway, hematopoietic cell lineage, JAK-STAT signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interaction, and 17 hub genes, such as JAK3, CCR1-3, CCR5-7, CCR8, were found.

Conclusions

Our study provides a remarkably detailed and comprehensive picture of asthma susceptibility genes and their interacting network. Further identification of these genes and molecular pathways may play a prominent role in establishing rational therapeutic approaches for asthma.
Etoricoxib versus indometacin in the treatment of Chinese patients with acute gouty arthritis: a randomized double-blind trial
Authors: Li Ting , Chen Shun-le , Dai Qing , Han Xing-hai , Li Zhan-guo , Wu Dong-hai , Zhang Xiao , Gu Jie-ruo , Yang Nan-ping , Sun Ling-yun , Zhang Miu-jia , Li Xing-fu , Bao Chun-de
Published: January 2024

Background

Acute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.

Methods

A randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n=178; ≥18 years of age) with acute gouty attack (<48 hours) were treated for 5 days with etoricoxib (120 mg/d; n=89) or indometacin (75 mg twice daily; n=89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2-5. Secondary end points included investigator assessments of tenderness and swelling, patient/investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).

Results

Etoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2-5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P=0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n=31) was less than the indometacin group (n=34).

Conclusions

Etoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).
Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China
Authors: WEN Deng-gui , YANG Yi , WEN Xiao-duo , SHAN Bao-en
Published: January 2024

Background

In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.

Methods

The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.

Results

A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P <0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P <0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P <0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P <0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.

Conclusions

The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.
Effects of Naoxintong on atherosclerosis and inducible nitric oxide synthase expression in atherosclerotic rabbit
Authors: Zhong Xiao-nan , Wang Hong-hao , Lu Zheng-qi , Dai Yong-qiang , Huang Jian-hua , Qiu Wei , Shu Ya-qing , Xu Wen , Cheng Chen , Hu Xue-qiang
Published: January 2024

Background

High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerosis processes. Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease. The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model.

Methods

Forty New Zealand white rabbits were randomly divided into five groups (n=8). Rabbits were fed a standard diet (group A), an atherogenic diet consisting of 79% standard feed+1% cholesterol+5% lard+15% egg yolk powder (group B), an atherogenic diet with Naoxintong 0.25 mg·-1·d-1 (group C), an atherogenic diet with Naoxintong 0.5 mg·-1·d-1 (group D), or atherogenic diet with Naoxintong 1.0 mg·-1·d-1 (group E) for 12 weeks.

Results

Supplemented administration of Naoxintong led to a down-regulation of cholesterol (CHOL) (P <0.001) and low-density lipoprotein (LDL) (P <0.001). The trend became more notable as the dose of Naoxintong increased; group C vs. group B (CHOL, P=0.568; LDL-cholesterol (LDL-C), P=0.119), group D vs. group B (CHOL, P=0.264; LDL-C, P=0.027), group E vs. group B (CHOL, P=0.028; LDL-C, P=0.002). Atherosclerotic lesions in aorta were reduced in Naoxintong groups (groups C, D, E) compared to group B. Group B had higher iNOS mRNA (P=0.001) and NO level (P <0.001) than group A. Compared with the atherogenic diet fed-rabbits, Naoxintong supplements decreased the expression of iNOS mRNA (P <0.001) and the NO level (P <0.001) in the vessel wall. Groups given a higher Naoxintong dose exhibited greater benefits. iNOS mRNA and NO levels seemed to be reduced in group C, although the difference did not quite reach statistical significance (iNOS mRNA, P=0.130; NO, P=0.038). iNOS mRNA and NO levels significantly decreased in group D (iNOS mRNA, P=0.019; NO, P=0.018) and group E (iNOS mRNA, P=0.004; NO, P <0.001).

Conclusion

Naoxintong has beneficial effects on atherosclerosis treatment by reducing expression of iNOS mRNA and the NO level in the vessel wall.
Clinical characteristics of patients with labyrinthine fistulae caused by middle ear cholesteatoma
Authors: YANG Juan-mei , CHI Fang-lu , HAN Zhao , HUANG Yi-bo , LI Yi-ke
Published: January 2024

Background

Labyrinthine fistula (LF) is a very common clinical complication mainly caused by middle ear cholesteatoma. Whether the presence of different degree LF caused by middle ear cholesteatoma aggravates neurosensory hearing loss (NSHL) and what is the degree of the hearing loss caused by LF were still under controversial. This study aimed to investigate whether the LF degree is correlative with the age distribution, disease duration and hearing loss degree for cholesteatomatous patients.

Methods

The files of 143 patients with middle ear cholesteatoma were selected and reviewed in a retrospective study. Seventy-eight patients with LF were divided into three types according to the degree of destruction of labyrinth. Sixty-five patients without LF were randomly chosen for control. Then, we compared the clinical characteristics of patients with or without labyrinthine fistulae caused by middle ear cholesteatoma.

Results

According to the study, cholesteatomatous patients with LF were older and suffered longer disease duration than those without LF. Hearing loss is severe with high frequencies both in patients with and without LF. Moreover, inner ear impairment is correlative with the degree of destruction in labyrinth, and more severe destruction in labyrinth follow the more severe symptoms correlative with inner ear impairment.

Conclusion

Surgical intervention should be performed as early as possible for these cholesteatomatous patients.
Temporal effect of local hyperthermia on murine contact hypersensitivity
Authors: ZHANG Lan , WANG Yi-ru , HONG Yu-xiao , XU Ya-qin , ZHANG Li , LI Xiao-dong , XIAO Ting , LU Dong-qing , CHEN Hong-duo , GAO Xing-hua
Published: January 2024

Background

The sensitization and elicitation phases are involved in the immunopathogenesis of contact hypersensitivity (CHS). Langerhans cells (LCs) are believed to play pivotal roles in the sensitization stage of CHS. Local hyperthermia on skin induces the migration as well as maturation of epidermal LCs. Although fever-range whole body hyperthermia and local hyperthermia at 43°C prior to sensitization were reported to suppress CHS, the effects of different temperatures and the timing sequence of local hyperthermia on CHS have not been tackled.

Methods

Local hyperthermia was applied to murine dorsal skin 3 days prior to, concurrent with, or 2 days post sensitization with fluorescein isothiocyanate (FITC) in BALB/c mice. Local hyperthermia temperatures at 37°C, 39°C, 41°C and 43°C were applied to mouse dorsal skin and the severity of CHS was calculated by measuring the swelling response of the challenged ears.

Results

Local hyperthermia at 39°C, 41°C and 43°C prior to sensitization reduced the severity of CHS, as compared with that at 37°C. The suppression of CHS was temperature dependant in that higher temperature had a stronger effect. On the contrary, the hyperthermia treatments, either concurrent with or post-sensitization, resulted in an enhanced temperature-dependant ear swelling response.

Conclusions

The severity of murine CHS could be influenced by local hyperthermia at the sensitization stage in a temperature dependant manner. The temporal effect of local hyperthermia suggested a novel factor in interpreting the severity of allergic contact dermatitis.
Assessment of the right and left ventricular function in patients with cor pulmonale using high-definition CT
Authors: Gao Yan , Qin Jian , Du Xiang-ying , Yang Jing , Li Kun-cheng
Published: January 2024

Background

Cor pulmonale is often associated with changes of structure and function of the right ventricle (RV) and thus further affects functional changes of the left heart. Our study aimed to assess the left ventricular (LV) and RV function in patients with cor pulmonale using high-definition CT (HDCT).

Methods

We prospectively studied 18 cor pulmonale patients determined by the pulmonary function test, clinical examination, chest radiograph, electrocardiogram, and echocardiogram. The subject group was compared to a control group consisting of 18 subjects. The RV and LV functions and RV myocardial mass (MM) were obtained by HDCT in the two groups. The results were compared between the two groups using the independent sample t test. Echocardiographic examination for cardiac function analysis was performed on the same day.

Results

The RV end-diastolic volume (EDV), RV end-systolic volume (ESV) and RV myocardial mass were significantly larger in the 18 cor pulmonale patients than in the control group (P<0.05). The right ventricular ejection fraction (RVEF) was significantly lower in the 18 cor pulmonale patients than in controls (P<0.01). The left ventricular EDV (LVEDV) and LVEF were significantly lower in cor pulmonale patients than in controls (P<0.01). There were strong correlations between MDCT and echocardiography, rRVEF=0.839 and rLVEF=0.916, respectively.

Conclusions

HDCT can accurately quantify RV and LV function. The right ventricular function is impaired in patients with cor pulmonale, while at the same time the left ventricular function is also impaired.
CD8+ Tc-lymphocytes immunodeviation in peripheral blood and airway from patients of chronic obstructive pulmonary disease and changes after short-term smoking cessation
Authors: Yu Mu-qing , Liu Xian-sheng , Wang Jian-miao , Xu Yong-jian
Published: January 2024

Background

Cigarette smoke induces an acute but persisting inflammation in peripheral blood and airway in chronic obstructive pulmonary disease (COPD), and CD8+ Tc-lymphocytes are considered as a key role in this process. We aimed to investigate the Tc-lymphocytes immunodeviation in system and local airway of COPD patients and changes of the immunodeviation after short-term smoking cessation.

Methods

Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were collected from 42 patients (14 COPD patients, 16 smokers with normal lung function and 12 nonsmokers), while PB and induced sputum (IS) were obtained from other 19 patients (10 quitting smokers and 9 continuing smokers) at baseline and follow-up respectively of 4-week smoking cessation. Percentages of CD8+ Tc-lymphocytes (%CD3+) and Tc1/Tc2 ratios were measured by flow cytometry.

Results

Percentages of CD8+ Tc-lymphocytes were higher in COPD patients than those in smokers and nonsmokers in both PB and BALF. Tc1/Tc2 ratio in PB and in BALF from COPD patients was greater than that from smokers and nonsmokers and negatively correlated with FEV1 %pre. When comparing the ratios between PB and BALF, significantly positive correlation was found in COPD patients. Furthermore, after 4-week smoking cessation, percentages of CD8+ Tc-lymphocytes in PB and IS in quitting smokers were decreased compared to that in baseline and continuing smokers, whereas Tc1/Tc2 ratios were not influenced.

Conclusions

CD8+ Tc1-trend immunodeviation profiles occurred in both system and local airway of COPD patients. This exceptional immunodeviation could not be relieved by short-term smoking cessation.
Atorvastatin reduces myocardial fibrosis in a rat model with post-myocardial infarction heart failure by increasing the matrix metalloproteinase-2/tissue matrix metalloproteinase inhibitor-2 ratio
Authors: AN Zhe , YANG Guang , HE Yu-quan , DONG Ning , GE Li-li , LI Shu-mei , ZHANG Wen-qi
Published: January 2024

Background

The cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear.

Methods

The left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation (SO) group, myocardial infarction model (Ml) group, and Ml-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin (HE) stained tissue. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 (MMP-2), and tissue matrix metalloproteinase inhibitor-2 (TIMP-2). Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation.

Results

The model of heart failure was established and the results of HE staining and Masson's trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the Ml group showed a significantly increased expression of type I and type III collagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/TIMP-2 ratio. Compared with the Ml group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang ll-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio.

Conclusions

These data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.
Effects of short-term active video game play on community adults: under International Classification of Functioning, Disability and Health consideration
Authors: Wei-Che Tseng , Ru-Lan Hsieh
Published: January 2024

Background

The effects of active video game play on healthy individuals remain uncertain. A person's functional health status constitutes a dynamic interaction between components identified in the International Classification of Functioning, Disability, and Health (ICF). The aim of this study was to investigate the short-term effects of active video game play on community adults using the ICF.

Methods

Sixty community adults with an average age of 59.3 years and without physical disabilities were recruited. Over 2 weeks, each adult participated in six sessions of active video game play lasting 20 minutes each. Participants were assessed before and after the intervention. Variables were collected using sources related to the ICF components, including the Hospital Anxiety and Depression Scale, Multidimensional Fatigue Inventory, Biodex Stability System, chair-rising time, Frenchay Activity Index, Rivermead Mobility Index, Chronic Pain Grade Questionnaire, Work Ability Index, and World Health Organization Quality of Life-Brief Version.

Results

Compared to baseline data, significantly reduced risk of a fall measured by Biodex Stability System and improvements in disability scores measured by the Chronic Pain Grade Questionnaire were noted. There was no significant change in the other variables measured.

Conclusion

Short-term, active video game play reduces fall risks and ameliorates disabilities in community adults.
Usefulness of lumen area parameters determined by intravascular ultrasound to predict functional significance of intermediate coronary artery stenosis
Authors: CUI Ming , ZHU Dan , GUO Li-jun , SONG Li-ying , ZHANG Yong-zhen , ZHANG Fu-chun , NIU Jie , WANG Gui-song , HAN Jiang-li , GAO Wei
Published: January 2024

Background

Coronary artery disease is the leading cause of death in China. Percutaneous coronary intervention is a recent milestone technology for treatment coronary artery disease. However, clinical decision making for patients with intermediate coronary stenosis is still controversial. We designed this study to assess the optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions.

Methods

We enrolled 141 patients with 165 intermediate coronary lesions located in vessels with a diameter ≥ 2.50 mm. IVUS of intermediate coronary lesions were performed before intervention. Pressure-derived fractional flow reserve (FFR) was measured at maximal hyperemia induced by adenosine infusion. An FFR <0.80 was considered as abnormal functional significance.

Results

For the overall 165 lesions, the mean FFR value was 0.84±0.09. The diameter of the stenosis by visual estimation on angiogram was (59.63±11.29)%. Minimum lumen diameter (MLD), minimum lumen area (MLA) and plaque burden (PB) were (2.00±0.36) mm, (3.88±1.34) mm2, (67.28±9.89)% respectively by IVUS measurements. An FFR <0.80 was seen in 43 lesions (30.5%). There was a moderate correlation between IVUS parameters and FFR, including MLD (r=0.372, P <0.001), MLA (r=0.442, P <0.001) and PB (r=-0.172, P <0.05). MLA was a predictor for FFR as a continuous variable independent of possible confounding variables (P <0.05), and MLA and PB, were predictors for FFR <0.80 as binary variables (P <0.05). The best cutoff value of MLA to predict FFR <0.80 was <3.15 mm2, with a 73.6% diagnostic accuracy; sensitivity 71.4%, specificity 67.0%, AUC=0.709, and P <0.001. The cutoff value of the PB to predict FFR <0.80 was 65.45%; sensitivity 82.6%, specificity 41.2%, AUC=0.644, and P <0.01. If both MLA and PB were taken into account, the negative predictive value and the positive predictive value were 88.7% and 64.8% respectively.

Conclusions

Anatomic measurements of intermediate coronary lesions obtained by IVUS showed a moderate correlation to FFR values. IVUS-derived MLA ≥3.15 mm2 may be useful to exclude FFR <0.80, but poor specificity limits its applicability for physiological assessment of lesions <3.15 mm2. MLA was one of many factors affecting coronary flow hemodynamics. Both MLA and PB should be taken into account when determining functional ischemia.
Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention
Authors: Tang Xiao-fang , Zhang Jia-hui , Wang Jing , Han Ya-ling , Xu Bo , Qiao Shu-bin , Wu Yong-jian , Chen Jue , Wu Yuan , Chen Ji-lin , Gao Run-lin , Yang Yue-jin , Yuan Jin-qing
Published: January 2024

Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.

Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74±32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).

Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
Effector cells derived from naive T cells used in tumor immunotherapy of mice bearing B16 melanoma
Authors: Wen Ming , Xu Weili , Ren Lili , Gao Fei , Cui Naipeng , Wen Junye , Li Xinjiang , Lin Lin , Ma Zhenfeng , Chen Baoping , Cai Jianhui
Published: January 2024

Background

Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.

Methods

C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells=2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-ã, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured.

Results

Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P <0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P <0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P <0.05).

Conclusion

Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.