Li et al. Journal of Physiological Anthropology
https://doi.org/10.1186/s40101-024-00364-5(2024) 43:17

ORIGINAL ARTICLE

Journal of
Physiological Anthropology

Open Access

Impact of high‑altitude hypoxia
on Helicobacter pylori‑induced gastritis
pathological manifestations and inflammatory
responses
Chunxia Li1,2, Xuehong Wang1,2 and Sen Cui1,3*   

Abstract
Background Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder.
Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies
elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impactof high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses.
Methods This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, AffiliatedHospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided
into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathologicalcharacteristics were collected, along with serum oxidative stress and inflammatory markers.
Results Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema,
enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes
show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients
have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore,individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1β, IL-6, and MDA, as well
as reduced serum SOD and GSH-Px activities.
Conclusions High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stressand inflammatory response induced by Hp infection.
Keywords High altitude, Hypoxia, Helicobacter pylori, Chronic gastritis*Correspondence:
Sen Cuicuisen4366@yeah.net
1
Clinical Medical College of Qinghai University, Xining, Qinghai Province,
China
2
Department of Gastroenterology, Qinghai University Affiliated Hospital,
Xining, Qinghai Province, China
3
Department of Hematology, Qinghai University Affiliated Hospital, 29
Tongren Road, Xining, Qinghai Province 810001, China

Introduction
Helicobacter pylori (Hp) is a gram-negative, microaerobic spirochete that colonizes and persists in the humangastric mucosa [1]. Hp infections are linked to gastroduodenal disorders such as chronic gastritis, peptic ulcers,
and gastric malignancies, as well as extragastric conditions including iron deficiency anemia, primary immune
thrombocytopenia, and vitamin B12 deficiency [2]. The
estimated global prevalence of Hp infection decreased
from 58.2% in the 1980–1990 period to 43.1% in the© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Li et al. Journal of Physiological Anthropology(2024) 43:17

2011–2022 period [3], with China maintaining a highprevalence rate of 44.2% [4]. Chronic gastritis, attributed mainly to Hp infection, is the predominant digestive
ailment in China [5]. Research indicates that nearly all
individuals infected with Hp progress to chronic active
gastritis [6], with some developing gastric mucosal atrophy and/or intestinal metaplasia following the Correa
pattern, leading to gastric cancer [7]. This progression
has a significant impact on the quality of life and overall
health of individuals.
The pathogenesis of gastritis induced by Hp infection
primarily involves Hp adhesion and colonization, releaseof virulence factors, and the initiation of oxidative stressand immune-inflammatory responses [8]. Environmental factors, alongside Hp and host factors, significantly
contribute to the onset and progression of this condition[9]. The Tibetan Plateau, mainly encompassing Tibet and
Qinghai, stands as China’s largest and the world’s highest
plateau, characterized by low pressure and oxygen levels. Prolonged exposure of plateau inhabitants to theseunique conditions leads to various pathophysiologicalchanges across multiple physiological systems, directly
impacting overall organism function. According to the
Sixth National Health Service Survey, conducted in 2018,
the top five prevalent diseases in Tibet are digestive system disorders, cardiovascular ailments, musculoskeletal
conditions, respiratory issues, and genitourinary illnesses,with digestive disorders showing the highest prevalence[10]. Despite the high prevalence of Hp infection andchronic gastritis in the Tibetan Plateau, there is a lack ofstudies elucidating the influence of plateau hypoxia on
Hp-induced gastritis. This study aims to investigate theimpact of plateau hypoxia on oxidative stress and inflammatory response of the gastric mucosa in patients with Hp
gastritis in the Tibetan Plateau region. The findings aim toestablish an experimental foundation for understanding
the pathogenesis of Hp gastritis in high-altitude regions.

Methods

Page 2 of 8

Inclusion criteria

We included patients between 18 and 65 years old who had
lived in Qinghai for their whole lifetime and whose endoscopic examination was consistent with chronic gastritis
with reference to the Chinese Guidelines for the Diagnosis
and Treatment of Chronic Gastritis (2022, Shanghai) [5].
Exclusion criteria

Patients were excluded if they had received proton pumpinhibitors (PPIs), H2-receptor antagonists (H2RAs),
potassium-competitive acid blockers (P-CABs), antibiotics, bismuth, micro-ecological agents, or traditional
Chinese medicines with antibacterial effects within theprevious 1 month. Patients with severe heterotrophic
hyperplasia, upper gastrointestinal hemorrhage, peptic
ulcers, malignant tumors, or gastric surgeries were also
excluded, as well as those with a combination of cardiac,
hepatic, or renal failure, hypertension, diabetes mellitus,
thyroid diseases, or autoimmune disorders. Additionally, pregnant and breastfeeding women, or those withserious bad habits such as smoking or alcoholism, werealso excluded.
Endoscopy and mucosal biopsy samples

Endoscopy was conducted on the patient in a fastingstate, revealing various pathological changes in the gastric mucosa, including mucosal punctate flaky erythema,diffuse erythema, hemorrhagic dots or plaques, enlarged
folds, white turbid mucus, and mucosal erosion. Two piecesof gastric mucosal tissue were taken from the antrum near
the lesser curvature, 2–3 cm from the pylorus.
Detection of Hp

The presence of Hp infection was confirmed through theuse of 13C-urea breath test and gastric mucosal immunohistochemistry. A positive outcome in either of thesetests indicates an Hp infection, while a negative result inboth tests rules out the presence of an Hp infection.

Study population and location

Histological assessment

A total of 100 with chronic gastritis were recruited fromthe Department of Gastroenterology at the AffiliatedHospital of Qinghai University between July 2023 andMarch 2024. The patients were categorized into fourgroups based on their residential altitude and Hp infection: Hp-negative chronic gastritis group ­(Hp− X group,n = 26) and Hp-positive chronic gastritis group ­(Hp+ X
group, n = 25) residing in the urban area of Xining City,
Qinghai Province (average elevation of approximately
2261 m); as well as Hp-negative chronic gastritis group­(Hp− G group, n = 22) and Hp-positive chronic gastritis group ­(Hp+ G group, n = 27) living at an elevationof ≥ 3500 m in Qinghai.

The gastric tissues were fixed in 4% paraformaldehyde,
dehydrated with alcohol, routinely embedded in paraffin, cut at 4 µm and stained with hematoxylin and eosin(H&E) for histopathology. Gastric histology was evaluated by 1 pathologist who was blinded to the other assays.
Polymorphonuclear neutrophils infiltration, which indicates active gastric inflammation, and mononuclear
inflammatory cells infiltration, which indicates chronic
gastric inflammation, were assessed on a 4-grade scale (0,1, 2, and 3, corresponding to none, mild, moderate, andsevere, respectively), according to the Updated Sydney
System [11] and Chinese Guidelines for the Diagnosis
and Treatment of Chronic Gastritis [5] (Table 1).

Li et al. Journal of Physiological Anthropology(2024) 43:17

Evaluation of oxidative stress and inflammation response

Blood samples were collected into serum separator tubes,
and serum was prepared by centrifuging (3000 r/min,
15 min) at 4 ℃. Commercial kits obtained from Wuhan
Abbkine Technology Co., Ltd. in China were utilized
for the evaluation of tumor necrosis factor-α (TNF-α),Interleukin (IL)-1β, and IL-6, malondialdehyde (MDA),
superoxide dismutase (SOD), and glutathione peroxidase(GSH-Px) levels in serum.
Statistical analysis

Data analysis and statistical graph generation were conducted using SPSS 27.0 and GraphPad Prism 9.5.1. The
statistical differences between groups were determinedby chi-square test or Kruskal–Wallis test followed by the
Bonferroni correction post-hoc test, or one-way ANOVA
followed by the least significant difference (LSD) posthoc test, or Kruskal–Wallis test followed by Dunnett’s T3
post-hoc test. A p-value of less than 0.05 was considered
statistically significant.
EthicsThis study was ethically approved by the Medical Ethics Committee of Qinghai University Affiliated Hospital(P-SL-2023–456). Prior to participation, all individuals
provided informed consent after being fully briefed on
the study and their rights.

Results
There was no statistically significant difference
between the pairs of groups in the mean age or genderof patients (Table 2)
Endoscopic observation of pathological changes in gastric mucosa

The study findings (Table 3) revealed a significantly
higher prevalence of diffuse erythema, enlarged folds,
and white turbid mucus in the gastric mucosa of the H­ p+−
X group compared to the H­ p X group (p < 0.05). However, there were no statistically significant differences in
the proportions of punctate erythema, hemorrhagic dots

Page 3 of 8or plaques, and mucosal erosions between the H­ p+ X−+and ­Hp X groups (p ≥ 0.05). The H­ p G group exhibiteda significantly higher proportion of gastric mucosa withdiffuse erythema, enlarged folds, and white turbid mucus
compared to the H­ p− G group (p < 0.05). Conversely, theproportions of punctate erythema, hemorrhagic dots or
plaques, and mucosal erosion did not differ significantly
between the ­Hp+ G and ­Hp− G groups (p ≥ 0.05). Furthermore, patients in the H­ p+ G group showed a notably
higher prevalence of diffuse erythema and fold enlargement than those in the H­ p+ X group (p < 0.05). Thesefindings suggest that patients with Hp gastritis typicallypresent with gastric mucosa characterized by diffuse erythema, fold enlargement, and white turbid mucus duringendoscopy. Additionally, the prevalence of diffuse erythema and enlarged folds in the gastric mucosa appears
to be elevated in patients with Hp gastritis in low-oxygen
plateau environments.
Histopathological evaluation of gastric tissue
Pathological changes in the gastric mucosa of patients ineach group were observed using HE staining (Fig. 1A)

Patients in the H­ p− X group and H­ p− G group exhibit gastric mucosal changes characterized by partial necrosis andshedding of epithelial cells, slight disorganization of glandular arrangement, and mild inflammatory cell infiltration. In
contrast, patients in the ­Hp+ X group show varying degrees
of congestion and swelling, along with epithelial cell necrosis

Table 2 General information of subjects participating in the
studyGroupsn

GenderAge(x̅ ± s, year)

Male

Female

Hp− X

26

11

15

48.23 ± 10.01

−

Hp G

22

9

13

46.23 ± 10.61

Hp+ X

25

12

13

47.48 ± 10.45

Hp+ G

27

17

10

43.26 ± 11.00

Table 1 Grading criteria for chronic inflammation and activity in gastric mucosa
Grade

Chronic inflammation

Activity0

The presence of fewer than five mononuclear inflammatory cells
per high-power field

Absence of neutrophil infiltration in the context of chronic inflammation

1

Mononuclear inflammatory cells are sparse and confinedto the superficial layer of the mucosa, not exceeding one-thirdof the mucosal layer

The mucosal lamina propria exhibits infiltration of a small numberof neutrophils

2Mononuclear inflammatory cells are more densely populated,
not exceeding two-thirds of the mucosal layer

Neutrophils are predominantly found in the mucosal layer and can beobserved within surface epithelial cells, crypt epithelial cells, or glandular epithelium

3

Mononuclear inflammatory cells are densely populated throughout the mucosal layer

Neutrophils are more densely packed, and in addition to moderate
observations, small abscesses may also be present

Li et al. Journal of Physiological Anthropology(2024) 43:17

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Table 3 Endoscopic observation of pathological changes in gastric mucosa
Characteristic

Hp− X(n = 26)

Hp− G(n = 22)

Hp+ X(n = 25)

Hp+ G(n = 27)

Punctate erythema

15 (57.7%)

13 (59.1%)

15 (60.0%)

7 (25.9%)

Diffuse erythema

0 (0.0%)1 (4.5%) #8 (32.0%) *#20 (74.1%)

Enlarged folds

0 (0.0%)3 (13.6%) #8 (32.0%) *#20 (74.1%)

White turbid mucus

1 (3.8%)2 (9.1%) #10 (40.0%) *13 (48.1%)

Hemorrhagic dots or plaques

2 (7.7%)5 (22.7%)

4 (16.0%)

9 (33.3%)

Mucosal erosion

10 (38.5%)

13 (59.1%)

16 (64.0%)

20 (74.1%)

Note: Data were analyzed by chi-square test followed by Bonferroni’s correction post-hoc test*p < 0.05 VS. ­Hp− X group; #p < 0.05 VS. ­Hp+ G groupand shedding, disordered glandular arrangement, and significant infiltration of inflammatory cells in the lamina propria.
Patients in the ­Hp+ G group display similar gastric mucosal
pathology as the ­Hp+ X group but with more severe manifestations. The scores of neutrophil infiltration and monocyte
infiltration were combined to assess gastric mucosal inflammation (Fig. 1B). The results suggest that the patients in the­Hp+ G group exhibited the highest gastric mucosal inflammation score among the four groups, followed by those in the­Hp+ X group. There was no statistically significant differencein gastric mucosal inflammation scores between patients inthe ­Hp− X group and the ­Hp− G group.
The grading of chronic inflammation in the gastric mucosa ofpatients in each group revealed significant differences (Table 4)

The ­Hp+ X group had a lower proportion of patientswith mild inflammation compared to the H­ p− X group(p < 0.05), but a higher proportion with moderate inflammation (p < 0.05). There was no statistically significant
difference in the proportion of patients in the H­ p− G
group who developed all levels of chronic inflammationin the gastric mucosa compared with those in the H­ p− X+
group (p ≥ 0.05). In the H­ p G group, the proportion ofpatients with mild inflammation was significantly lower
than in the H­ p− G group (p < 0.05) and ­Hp+ X group(p < 0.05), while the proportion with severe inflammation was significantly higher than in the ­Hp− G group(p < 0.05) and ­Hp+ X group (p < 0.05).
Gastric mucosal active inflammation was assessed in eachgroup (Table 5), revealing a significantly lower incidence
of inactive inflammation in the ­Hp+ X group comparedto the ­Hp− X group (p < 0.05)

Conversely, the H­ p+ X group exhibited a significantly
higher rate of mild active inflammation compared to the­Hp− X group (p < 0.05). There was no statistically significant
difference in the proportion of patients in the ­Hp− G group
who developed all levels of active inflammation in thegastric mucosa compared with those in the ­Hp− X group(p ≥ 0.05). In the ­Hp+ G group, the prevalence of inactive
inflammation was significantly lower than in the H­ p− G
group (p < 0.05), while the rates of mild active inflammation
were significantly lower than in the ­Hp+ X group (p < 0.05).
Moreover, the incidence of moderate active inflammation
was significantly higher in the ­Hp+ G group compared toboth the ­Hp− G and H­ p+ X groups (p < 0.05).

Fig. 1 A HE staining of the gastric tissues (× 200). Scale bar: 50 µm. B Inflammatory scores of gastric tissue sections in each group. Data wererepresented as mean ± SEM and analyzed by Kruskal–Wallis test followed by Dunnett’s T3 post-hoc test. **p < 0.01, ns, not significant

Li et al. Journal of Physiological Anthropology(2024) 43:17

Page 5 of 8

Table 4 Grading of chronic inflammation of the gastric mucosa
Groupsn

Chronic gastritis severity
0

1

2

3
0 (0.0%)

Hp− X

26

0 (0.0%)20 (76.9%)

6 (23.1%)

Hp− G

22

0 (0.0%)12 (54.5%) #10 (45.5%)

*#

+

Hp X

25

0 (0.0%)9 (36.0%)+27

0 (0.0%)1 (3.7%)

Hp G

15 (60.0%)

0 (0%) #*16 (59.3%)

1 (4.0%) #10 (37.0%)

Note: Data were analyzed by Kruskal–Wallis test followed by Bonferroni’s
correction post-hoc test*p < 0.05 VS. ­Hp− X group; #p < 0.05 VS. ­Hp+ G group

Table 5 Grading of active inflammation of the gastric mucosa
Groupsn

Activity intensity
0

1

2

3

Hp− X

26

22 (84.6%)

4 (15.4%)

0 (0.0%)0 (0.0%)

Hp− G

22

15 (68.2%) #5 (22.7%)2 (9.1%) #0 (0.0%)

Hp+ X

25

2 (8.0%) *17 (68.0%) *#6 (24.0%) #0 (0.0%)

Hp+ G

27

0 (0.0%)6 (22.2%)

19 (70.4%)

2 (7.4%)

Note: Data were analyzed by Kruskal–Wallis test followed by Bonferroni’s
correction post-hoc test*p < 0.05 VS. ­Hp− X group; #p < 0.05 VS. ­Hp+ G group

Effects of hypoxia on Hp‑induced oxidative stress in gastricSerum oxidative stress indexes were assessed in patients
across different groups (Fig. 2), revealing that individuals
in the H­ p+ X group exhibited significantly elevated MDA
levels compared to those in the ­Hp− X group (p < 0.01),
along with notably decreased SOD and GSH-Px activities(p < 0.01). Similarly, patients in the ­Hp− G group demonstrated significantly higher MDA levels than those in
the ­Hp− X group (p < 0.01), coupled with decreased SOD
and GSH-Px activities (p < 0.01). Furthermore, individuals in the ­Hp+ G group displayed significantly higher
MDA levels than both the ­Hp− G group (p < 0.01) and­Hp+ X group (p < 0.01), with concomitantly lower SOD
and GSH-Px activities compared to the ­Hp− G group(p < 0.01) and ­Hp+ X group (p < 0.01). These findings suggest that hypoxia exposure exacerbates oxidative stressinduced by Hp infection.
Effects of hypoxia on Hp‑induced inflammatory response
in gastricSerum inflammatory factors were assessed in patients
across different groups (Fig. 3). The findings revealed
significantly elevated levels of TNF-α, IL-1β, and IL-6 inpatients from the ­Hp+ X group compared to those in the­Hp− X group (p < 0.01). Conversely, no statistically significant variances were observed in the levels of TNF-α,
IL-1β, and IL-6 between patients in the H­ p− G and H­ p−
X groups (p ≥ 0.05). Remarkably, patients in the ­Hp+ G

group exhibited notably higher levels of TNF-α, IL-1β,
and IL-6 compared to both the H­ p− G group (p < 0.01)+
and the ­Hp X group (p < 0.01). These results suggest thathypoxia exposure exacerbates the release of pro-inflammatory factors induced by Hp infection.

Discussion
The diverse pathological manifestations of Hp infection
stem from the intricate interplay of bacterial virulence,
host genetics, and environmental influences, giving rise
to various chronic gastritis phenotypes [8]. High-altitudeenvironments are widely distributed globally, with anestimated 81.6 million people residing in regions above
2500 m [12]. A study investigating patients with digestive symptoms in high-altitude regions of India found ahigher prevalence of Hp infection and gastritis severity
through histopathology and endoscopy [13]. Furthermore, research indicates a notably elevated incidence ofgastric perforation in young soldiers stationed in highaltitude areas, possibly linked to the high prevalenceof gastritis and Hp infection among residents in theseregions [14]. Therefore, the high incidence of Hp-related
gastritis in high-altitude regions underscores the importance of studying the pathogenesis of Hp-related gastritis
under hypoxic conditions for maintaining gastrointestinal health in high-altitude populations. Our study aims toinvestigate the impact of a high-altitude hypoxic environment on Hp infection-induced oxidative stress, inflammatory response, and gastric mucosal damage.
Chronic gastritis typically presents endoscopically withmanifestations such as mucosal erythema, edema, andincreased mucus, often accompanied by hemorrhagic
dots or plaques and erosion [15]. Our study revealed ahigher prevalence of diffuse erythema, enlarged folds,
and white turbid mucus in the gastric mucosa of patientsin the ­Hp+ X and ­Hp+ G groups compared to those in
the ­Hp− X and H­ p− G groups, respectively. Moreover, the+­Hp G group exhibited a significantly higher incidenceof diffuse erythema and fold enlargement in the gastricmucosa compared to the H­ p+ X group. These findings
suggest that patients with Hp gastritis typically exhibit
diffuse erythema, fold swelling, and white turbid mucus
during endoscopy. In high-altitude, low-oxygen environments, the presence of Hp infection should be consideredwhen observing diffuse erythema and fold enlargementin the gastric mucosa of patients with chronic gastritis.
Chronic gastritis is an inflammatory lesion of the gastric mucosa characterized by lymphocyte and plasma cell
infiltration, and when accompanied by neutrophil infiltration it is called chronic active gastritis [16]. Our findings showed that patients in the ­Hp+ G group had thehighest gastric mucosal inflammation score, suggestingthat hypoxic exposure aggravates Hp gastritis. We furtherLi et al. Journal of Physiological Anthropology(2024) 43:17

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Fig. 2 The levels of MDA (A), SOD (B), GSH-Px (C). Data were represented as mean ± SEM and analyzed by one-way ANOVA followed by LSD
post-hoc test.**p < 0.01

Fig. 3 The levels of TNF-α (A), IL-1β (B), IL-6 (C). Data were represented as mean ± SEM and analyzed by one-way ANOVA followed by LSD post-hoc
test. **p < 0.01, ns, not significant

Li et al. Journal of Physiological Anthropology(2024) 43:17

Page 7 of 8

graded for the degree of chronic inflammation and thedegree of active inflammation, and the results suggested
that patients in the H­ p+ G group had the lowest percentage of gastric mucosa with mild chronic inflammationand the highest percentage with severe chronic inflammation. In addition, patients in the ­Hp+ G group had thelowest rate of mild active inflammation and the highest
rate of moderately active inflammation in the gastricmucosa. The above findings suggest that hypoxia exposure exacerbates the degree of chronic inflammation andactive inflammation in the gastric mucosa of patientswith Hp gastritis.
When Hp infects gastric mucosal epithelial cells, its
type IV secretion system facilitates the delivery of virulence factors into the host cells [17]. Subsequently, thesefactors are recognized by pattern recognition receptors,
triggering immunoinflammatory and oxidative stresssignaling pathways [18, 19]. This activation leads to therelease of pro-inflammatory cytokines and an accumulation of reactive oxygen species and reactive nitrogenspecies, ultimately causing gastric mucosal damage andexacerbating Hp-induced gastritis. Our findings indicatethat individuals in the ­Hp+ G group exhibited elevatedlevels of serum TNF-α, IL-1β, IL-6, and MDA, alongwith reduced activities of serum SOD and GSH-Px. Thissuggests that hypoxic exposure intensifies the oxidative
stress and inflammatory response provoked by Hp infection. Hypoxia-inducible factor-1α (HIF-1α), a widelydistributed transcriptional activator in mammals andhumans during hypoxia, is known to play a crucial rolein the pathogenesis of various hypoxia-related diseases[20]. Although HIF-1α is typically absent in normal gastric mucosa, its expression intensifies progressively from
Hp-induced gastritis to adenocarcinoma, indicating a
potential molecular mechanism through which hypoxia
exacerbates Hp infection-related gastric disorders [21].
The limitation of this study was that the sample size
was relatively small, which may not be fully representative of the overall situation of patients with Hp-induced
gastritis in high-altitude area. Future studies may consider conducting a large-scale, multicenter empirical
study based on enlarging the sample size and considering the matching of samples between groups to verify thefindings of this study.

be an effective strategy to alleviate Hp-associated gastritis conditions at high altitude. For this population, clinicians may consider antioxidants as an adjunctive therapy
to mitigate gastric mucosal damage caused by oxidative stress and inflammation. This research offers novel
insights for the prevention and management of chronic
gastritis in plateau areas, enhancing comprehension andmanagement of the impact of high-altitude hypoxia on
Hp infection and associated conditions.

Conclusion
In conclusion, high-altitude hypoxia exacerbates gastricmucosal inflammation and injury by enhancing oxidative stress and inflammatory response induced by Hp
infection. Therefore, increased emphasis on Hp detection and treatment is warranted for individuals residing
in plateau regions to mitigate the prevalence and gravityof chronic gastritis. In addition, antioxidant therapy may

Received: 4 April 2024 Accepted: 26 June 2024

Abbreviations
Hp	
Helicobacter pylori
MDA	Malondialdehyde
SOD 	Superoxide dismutase
GSH-Px	Glutathione peroxidase
TNF-α	Tumor necrosis factor-αIL-1β	Interleukin-1β
IL-6	Interleukin-6
HIF-1α	Hypoxia-inducible factor-1αLSD	Least significant difference
Acknowledgements
Not applicable.
Authors’ contributions
Chunxia Li: study concept and design, data analysis and interpretation, andarticle drafting. Xuehong Wang: participated in data analysis and interpretation and in critically revising the article for intellectual content. Sen Cui: study
concept and design, critical revision of the article for intellectual content. All
authors have read, reviewed, revised, and approved the final manuscript.
Funding
This study was supported by the “Thousand Talents Program” for High-end
Innovation of Qinghai Province (2017–5) and the Construction Project ofProvincial Clinical Key Specialty in Qinghai Province (2022–118).
Availability of data and materials
The datasets used and/or analyzed during the current study are available fromthe corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
This study was conducted according to the principles expressed in the
Declaration of Helsinki and approved by the Medical Ethics Committee of
Qinghai University Affiliated Hospital (P-SL-2023–456). Prior to participation,
all individuals provided informed consent after being fully briefed on the
study and their rights.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.

References
1. Duan M, Li Y, Liu J, et al. Transmission routes and patterns of Helicobacter
pylori. Helicobacter. 2023;28:e12945.
2. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut.
2022;71(9):1724–62.

Li et al. Journal of Physiological Anthropology

3.
4.
5.

6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.

(2024) 43:17

Li Y, Choi H, Leung K, Jiang F, Graham DY, Leung WK. Global prevalenceof Helicobacter pylori infection between 1980 and 2022: a systematic
review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8:553–64.
Ren S, Cai P, Liu Y, et al. Prevalence of Helicobacter pylori infection in
China: a systematic review and meta-analysis. J Gastroenterol Hepatol.
2022;37:464–70.
Chinese Society of Gastroenterology, Cancer Collaboration Group ofChinese Society of Gastroenterology, Chinese Medical Association.
Guidelines for diagnosis and treatment of chronic gastritis in China.
Shanghai). J Dig Dis. 2022;2023(24):150–80.
Rugge M, Savarino E, Sbaraglia M, Bricca L, Malfertheiner P. Gastritis: The
clinico-pathological spectrum. Dig Liver Dis. 2021;53:1237–46.
Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on
Helicobacter pylori gastritis. Gut. 2015;64:1353–67.
Malfertheiner P, Camargo MC, El-Omar E, et al. Helicobacter pylori infection. Nat Rev Dis Primers. 2023;9:19.
de Brito BB, da Silva FAF, Soares AS, et al. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J Gastroenterol.
2019;25:5578–89.
Deng R, Labasangzhu, Zhaxideji, et al. Illness prevalence rate in Tibet,
China: data from the 2018 National Health Service Survey. BMC Public
Health. 2020;20:955.
Stolte M, Meining A. The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol. 2001;15:591–8.
Tremblay JC, Ainslie PN. Global and country-level estimates ofhuman population at high altitude. Proc Natl Acad Sci U S A.
2021;118(18):e2102463118.
Sharma PK, Suri TM, Venigalla PM, et al. Atrophic gastritis with high prevalence of Helicobacter pylori is a predominant feature in patients withdyspepsia in a high altitude area. Trop Gastroenterol. 2014;35(4):246–51.
Pawar A, Sinha V, Sharma P, Sinha DK. High altitude area - a risk factor for
gastric perforation? : A case series. Int J Surg Case Rep. 2018;53:429–32.
Yoshii S, Mabe K, Watano K, et al. Validity of endoscopic features for the
diagnosis of Helicobacter pylori infection status based on the Kyoto classification of gastritis. Dig Endosc. 2020;32:74–83.
Pennelli G, Grillo F, Galuppini F, et al. Gastritis: update on etiological features and histological practical approach. Pathologica. 2020;112:153–65.
Cover TL, Lacy DB, Ohi MD. The Helicobacter pylori cag type IV secretion
system. Trends Microbiol. 2020;28:682–95.
Yang H, Hu B. Immunological perspective: Helicobacter pylori infection
and gastritis. Mediators Inflamm. 2022;2022:2944156.
Han L, Shu X, Wang J. Helicobacter pylori-mediated oxidative stress andgastric diseases: a review. Front Microbiol. 2022;13:811258.
Chandel NS, Simon MC. Hypoxia-inducible factor: roles in development,
physiology, and disease. Cell Death Differ. 2008;15(4):619–20.
Griffiths EA, Pritchard SA, Valentine HR, et al. Hypoxia-inducible factor1alpha expression in the gastric carcinogenesis sequence and its
prognostic role in gastric and gastro-oesophageal adenocarcinomas. Br J
Cancer. 2007;96(1):95–103.

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