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1.
Artículo en Chino | WPRIM | ID: wpr-1026947

RESUMEN

Objective:To investigate the Helicobacter pylori ( H. pylori) infection of Tibetan families and individuals in the Western Sichuan Plateau region and explore the related factors which affected H. pylori infection. Methods:This was a single-center cross-sectional study. Questionnaires were collected from 50 Tibetan families including 155 individuals in Western Sichuan Plateau region during March to May 2023. The 13C-urea breath test was performed to confirm the current infection status of participants. Binary logistic regression were used to analyze the related factors associated with H. pylori infection. Results:Among the 50 Tibetan households, the individual-based H. pylori infection rate was 47.10%(73/155), with two out of nine children and 48.63%(71/146) adults infected. The age group of 18 to 40 years had the highest infection rate (55.00%, 11/20). The prevalence of infection based on family was 80.00%(40/50), of which 16.00%(8/50) had all family members infected. Of the 59 couples surveyed, 23.73%(14/59) were both infected, and 45.76%(27/59) had one person infected. Of the six families which had children and adolescents, two households had their children infected. Logistic regression analysis showed that size of the family was a factor related to H. pylori infection (odds ratio=3.038, 95% confidence interval 1.043 to 10.491, P=0.042). Conclusions:The family-based H. pylori infection rate is relatively high in Tibetan residents in the Western Sichuan Plateau, and larger family size is related with higher risk of H. pylori infection within the family.

2.
Immunological Journal ; (12): 1021-1027, 2023.
Artículo en Chino | WPRIM | ID: wpr-1019389

RESUMEN

Chronic inflammation induced by Helicobacter pylori is considered to be one of the main causes of gastric cancer,and CagA is a main virulence factor of H.pylori.The study aimed to investigate the role and mechanism of CagA in host inflammatory response.Mass spectrometry was used to identify the interacting proteins of CagA in AGS cells.By immunoprecipitation and immunofluorescence,the interaction was validated.Pathway expression was detected by immunoblotting after knockdown by using siRNA,and mRNA levels of inflammatory cytokines were detected by quantitative PCR.CagA-induced inflammatory responses were detected in clinical samples using hemoglobin-eosin staining(H&E).Data showed that CagA interacted with SHARPIN.And CagA activated the NF-κB signaling pathway and upregulated the mRNA and protein levels of the inflammatory cytokines IL-6,IL-8,and TNF-α,as compared with the CagA knockout strain(all P<0.05).Knockdown of SHARPIN by siRNA reduced inflammation levels and partially inhibit NF-κB signaling.In clinical samples,CagA-positive samples exhibited stronger inflammatory responses.To sum up,CagA promoted the host inflammatory response,and CagA-induced inflammatory response was reduced when SHARPIN was partially inhibited,suggesting that CagA activates the NF-κB signaling pathway through binding to SHARPIN.

3.
Artículo en Chino | WPRIM | ID: wpr-1021120

RESUMEN

Background:There is no comparison of the current status of Helicobacter pylori(Hp)infection in different ethnic groups in terms of families and their individuals.Aims:To investigated for the first time the status of Hp infection in Tibetan and Han Chinese families at the household level.Methods:A questionnaire was used to investigate factors associated with Hp in 50 Tibetan families in Ya'an,Sichuan Province,and 50 Han Chinese families in Chongqing Municipality.13C-urea breath test was used to detect Hp infection.Results:The individual and household Hp positivity rates of the Tibetan population in southwest China were 47.10%and 80%,which were significantly higher than those of the Han Chinese,which were 27.81%and 58%(P<0.05).However,the difference between Han and Tibetan in individual and household infection rates was not statistically significant.There are differences between Han Chinese and Tibetans in terms of infection status,geography,economic conditions,living habits and levels of hygiene.Infection was concentrated in certain family groups rather than being evenly distributed in the population.Conclusions:The current detection rate of Hp infection in individuals and families of Tibetan residents is significantly higher than that of Han Chinese,while the proportion of infected individuals is not statistically different.Transmission of Hp is characterized by family aggregation.There are differences in infection status,geographical environment,economic conditions,living habits and hygiene levels between Chinese and Tibetan families.

4.
Artículo en Chino | WPRIM | ID: wpr-1016111

RESUMEN

Background: The benefits and risks of eradicating Helicobacter pylori (Hp) should be balanced in aged people. Aims: To investigate the efficacy, safety and antibiotic resistance status of Hp eradication treatment in the elderly. Methods: Four cohorts of subjects who received Hp eradication treatment in randomized controlled trials conducted in Chongqing Daping Hospital were reviewed; the demographic and clinical data were extracted and recorded. Propensity score matching was performed to select comparable elderly group (≥60 years old) and non-elderly group (0.05). Furthermore, there were no significant differences in the Hp eradication rates in terms of gender, cigarette smoking, alcohol consumption, comorbidities (hypertension, diabetes, surgical history, and inflammation), compliance, etc. in the elderly group (all P> 0.05). But in retreated elderly subjects, the resistance rate of clarithromycin was higher than that in naïve elderly subjects (P<0.05). Smoking and poor compliance were identified as independent risk factors for Hp eradication by multivariate Logistic regression analysis. Conclusions: Hp eradication in the elderly demonstrates comparable efficacy and safety with non-elderly subjects. Clarithromycin-containing regimens are not recommended for empirical retreatment in aged people.

5.
Artículo en Chino | WPRIM | ID: wpr-1016132

RESUMEN

Background: The increasing in antibiotic resistance of Helicobacter pylori (Hp) has become the main cause leading to the decreasing of the eradication rate for Hp treatment. Aims: To investigate the risk factors of drug resistance of Hp. Methods: Data on 396 patients with Hp infection from Dec. 2016 to Mar. 2021 at Army Medical University were retrospectively analyzed. Drug susceptibility test was used to evaluate the resistance of 6 antibacterial drugs (metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and furazolidone). Unconditional Logistic regression was used to investigate the risk factors affecting Hp antibiotic resistance. Results: In 396 patients with Hp infection, the resistance rates of metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline and furazolidone were 96.5%, 45.5%, 41.9%, 0.3%, 0.3% and 0, respectively. Multivariate analysis showed that previous regimen containing clarithromycin was a risk factor for clarithromycin resistance (P 40 years old was a risk factor for levofloxacin resistance (P< 0.001). Conclusions: The resistance rates of metronidazole, clarithromycin and levofloxacin are relatively high, and regimens containing these antibiotics should be avoided without the support from drug susceptibility results, especially in patients who have accepted clarithromycin‑containing regimen or more than 40 years old. Amoxicillin, tetracycline and furazolidone should be recommended preferentially for Hp treatment empirically.

6.
Artículo en Chino | WPRIM | ID: wpr-1016244

RESUMEN

Background: Helicobacter pylori (Hp) infection is related to the occurrence of many upper digestive tract diseases, and the eradication rate has been decreasing year by year. Aims: To investigate the risk factors affecting initial eradication rate of Hp infection. Methods: Clinical data of 428 patients with Hp infection were retrospectively analyzed. Four regimens (14-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 10-day esomeprazole 20 mg + amoxicillin 750 mg, qid; 14-day esomeprazole 20 mg + amoxicillin 1 000 mg, tid; 14-day esomeprazole 20 mg + bismuth 220 mg + amoxicillin 1 000 mg + clarithromycin 500 mg, bid) were given, and effect of antibiotic resistance on Hp eradication was analyzed, the relevant risk factors affecting the eradication rate of Hp were investigated. Results: The eradication rate of ITT analysis was 86.4%, PP analysis was 87.6%. The eradication rates of 4 regimens for ITT analysis were 90.8%, 79.8%, 82.7%, 91.9%, respectively, and were 90.8%, 81.2%, 85.1%, 92.7% for PP analysis, respectively. The antibiotic resistance rate was 30.3%, 97.4% and 36.8% for clarithromycin, metronidazole and levofloxacin, respectively. The recurrence rate of 116 patients was 4.3% after one year of eradication. Smoking, poor compliance, CYP2C19 gene polymorphism were risk factors for eradication rate of Hp (P<0.05). Conclusions: Smoking, poor compliance and ultra-rapid metabolizers, extensive metabolizers of CYP2C19 gene polymorphism can reduce Hp eradication rate. In clinical practice, patient education should be strengthened to urge patients to quit smoking. The quality of follow-up should be improved and proton pump inhibitor that has less impact on CYP2C19 gene polymorphism should be used, thereby increase the Hp eradication rate.

7.
Journal of Clinical Hepatology ; (12): 1799-1804, 2020.
Artículo en Chino | WPRIM | ID: wpr-825038

RESUMEN

ObjectiveTo analyze the articles on endoscopic retrograde cholangiopancreatography (ERCP), an important method for minimally invasive treatment of biliary and pancreatic diseases, published worldwide, and to investigate the status, hotspots, and development trends in this field. MethodsThe web of science core collection database in Web of Science platform was selected to search by the subject words “TS = (Cholangiopancreatography, Endoscopic Retrograde)”, for the articles published from January 1, 2015 to December 31, 2019, and the literature type was selected as “article”. CiteSpace 5.6.R2 (64-bit) was used to analyze the authors, key words, institutions, countries (regions), and references and plot visualized maps. ResultsA total of 1535 articles on ERCP were included. The analysis showed that Hiroyuki Isayama had the highest number of published articles, followed by Yousuke Nakai and Takeshi Ogura, and University of Tokyo had the highest number of published articles, followed by Shanghai Jiao Tong University and University of Ulsan College of Medicine. Moreover, the US, Japan, and China were the top three countries from the aspect of the number of published articles in the recent 5 years, and ERCP, complication, and risk factor were the key words with the highest frequency in the recent 5 years. The most frequently cited articles mainly focused on the complications of ERCP and related consensus or guidelines. ConclusionThe main research hotspots and trends in the field of ERCP are related factors and clinical prevention of ERCP-related complications.

8.
Artículo en Chino | WPRIM | ID: wpr-607890

RESUMEN

Background:Esophageal non-variceal hemorrhage is relatively uncommon in clinical,however,it can be life-threatening in severe cases. Thus,retrospective analysis of esophageal non-variceal hemorrhage could provide important evidence for its diagnosis and treatment. Aims:To analyze the clinical characteristics of esophageal non-variceal hemorrhage. Methods:A total of 175 cases of esophageal non-variceal hemorrhage from January 2006 to December 2016 at Daping Hospital were enrolled. Gender,age,cause of bleeding,location of bleeding,season of onset,treatment and prognosis were retrospectively analyzed. Results:The ratio of male to female was 3. 5: 1 in 175 patients with esophageal non-variceal hemorrhage,73. 1% of patients were middle-aged and elderly. The main cause of bleeding of esophageal non-variceal hemorrhage were cardiac mucosal laceration syndrome (46. 9%),esophageal cancer (23. 4%),esophageal ulcer (12. 6%)and esophageal foreign body (12. 0%). The most common site of bleeding was lower esophagus (70. 9%). Fifty-one patients accepted endoscopic treatment or surgery. After treatment,142 patients (81. 1%)were cured or improved,and death was occurred in 27 patients (15. 4%). Conclusions:The incidence of esophageal non-variceal hemorrhage is higher in male than in female,and is commonly seen in middle-aged and elderly patients. The most common cause of bleeding of esophageal non-variceal hemorrhage is cardiac mucosal laceration syndrome,and the most common site of bleeding is lower esophagus. Medicine combined with endoscopic treatment is effective for most of the patients.

9.
Chinese Journal of Digestion ; (12): 462-465, 2017.
Artículo en Chino | WPRIM | ID: wpr-612055

RESUMEN

Objective To explore the clinical characters,treatment and prognosis of gastrointestinal Dieulafoy lesion in China.Methods Dieulafoy was used as search term,the literatures about Chinese patients with Dieulafoy lesions from January 1998 to October 2016 were retrieved in the Chinese literature library including China National Knowledge Infrastructure,VIP network,Wanfang database and China Biology Medicine disc,and a total of 515 literatures,5 145 patients were enrolled and analyzed.The gender,age,geographical distribution,location of the lesion,treatment and prognosis of the disease were summarized.Results Among the 5 145 patients (male 3 959,female 1 186) with Dieulafoy disease,the ratio of male to female was 3.34∶1.00.The age was from 3 to 95 years,and mean age was 51 years.The lesion location was mainly in stomach (88.82%,4 570/5 145) and second was small intestine (8.28%,426/5 145).In stomach,the lesions were mainly located in gastric corpus,fundus and cardia.The small intestinal Dieulafoy lesions were mainly located in duodenum.The main manifests were sudden hematemesis,melena,and hematochezia.The treatments mainly was endoscopic treatment (72.56%,3 733/5 145),and second was surgery (25.27%,1 300/5 145).Among the5 145 patients withDieulafoy disease,5 099 patients (99.11%) were cured and 46 patients (0.89%) died.The proportions of endoscopic treatment,interventional therapy and first endoscopic treatment within 24 hours in tertiary hospitals were all higher than those of nontertiary (all P<0.01).The cure rate of tertiary hospitals (99.22%,3 674/3 793) was significantly higher than that of nontertiary hosptials (98.54%,1 421/1 442) (x2 =0.89,P<0.05) and the mortality was significantly lower than that of nontertiary hospitals (P< 0.05).Conclusions The male is more susceptible to Dieulafoy lesion which occurred at any age than the female in China.The predilection sites of Dieulafoy lesion were stomach and duodenum.The primary treatments were endoscopic treatment and surgery,and the disease usually had a good prognosis.

10.
Artículo en Chino | WPRIM | ID: wpr-621496

RESUMEN

Objective Retrospectively analyzed the data of patients with delayed bleeding after colorectal polypectomy,summarized the risk factors and treatment methods of bleeding patients,and provided the basis for further prevention and treatment of postoperative delayed bleeding.Methods Collected the clinical data of 1 243 patients who were admitted into the department of gastroenterology of third affiliated hospital of the third military medical university and accepted polypectomy with colonoscopy from January 2014 to December 2016.Divided these patients into the bleeding group and the non-bleeding group according to whether there was delayed bleeding after surgery.The age,size of polypus,location of polypus,postoperative pathology of the two groups were compared and the postoperative treatment of bleeding was evaluated.Results Among the 1 243 patients underwent colorectal polypectomy,there were 14 cases of delayed bleeding,and the incidence was 1.13%.In the bleeding group,there was 1 case of secondary delayed bleeding and 2 cases of bloody stool after hemostasis for the delayed bleeding.Delayed bleeding occurred at (4.73±2.49)days after surgery.The predilection site of of polypus was rectum in the bleeding group (7/14,50%), and the diameter of polypus was (16.65±4.91)mm in the bleeding group,which was lager than (8.07±4.23)mm in the non-bleeding group with statistical difference (P<0.05).The proportion of hypertensive and diabetic patients in the bleeding group was significantly higher than that in the non-bleeding group (P<0.05).Juvenile polyps and tubular adenoma with high grade intraepithelial neoplasia were more common in the bleeding group(P<0.05).The bleeding group achieved good hemostatic effect by purse suture,hemostatic clip,electrocautery or injection hemostasis.Conclusion Older age,hypertension and diabetes,lager size of polypus,rectum polypus,juvenile polyps and tubular adenoma with high grade intraepithelial neoplasia were risk factor for delayed bleeding.In the event of delayed bleeding,different choice of purse suture,hemostatic clip,electrocautery or injection hemostasis according to different wounds can achieve the desired effect.

11.
Chongqing Medicine ; (36): 3858-3860, 2014.
Artículo en Chino | WPRIM | ID: wpr-459564

RESUMEN

Objective To investigate the correlation between Helicobacter pylori (HP) infection-associated gastritis and the ap-optotic genes in gastric mucosa .Methods Forty-five patients with chronic gastritis were registrated in our study from November 2013 to December 2014 .HP infection status in the patients was detected by using urease test and 13C-urea breath test .The degree of gastritis in the gastric mucosa with HP infection was confirmed via histopathology .qRT-PCR was used to measure the mRNA ex-pressions of Bax ,Bak and Bcl-2 in the gastric mucosa with HP infection and matched normal gastric mucosa .Person analysis was used to assess the correlation between the HP infection-associated gastritis and the mRNA expressions of Bax ,Bak and Bcl-2 in the gastric mucosa .Results Forty-five patients with HP infection in antrum and 45 patients (100% ) with chronic antrum gastritis were identified ,including 28 patients (62 .2% ) with light gastritis ,16 patients (35 .6% ) with moderate gastritis ,1 patient (2 .0% ) with severe gastritis .9 patients (20 .0% )with metaplasia ,5 patients(11 .1% ) with low grade intraepithelial neoplasms .The urease tests were negative in the gastric body of 45 patients ,6 patients (13 .3% )were mild chronic gastritis in the body ;Patient with meta-plasia and intrapithelial gastritis was not found .The Bax expression in the HP-infected gastric mucosa was markedly increased when compared with the normal gastric mucosa (P0 .05) .Conclusion HP infec-tion-associated gastritis positively correlated with the expressions of apoptotic genes in gastric mucosa ,suggesting that HP infection might result in increasing the Bax expression and further enhancing the cell apoptosis .

12.
Military Medical Sciences ; (12): 714-718,744, 2014.
Artículo en Chino | WPRIM | ID: wpr-600197

RESUMEN

Objective To isolate and purify VacA protein secreted by Helicobacter pylori or recombinant VacA , and to investigate the effect of VacA-induced cell vacuolar change and apoptosis .Methods VacA proteins were separated and pu-rified from the culture supernatant of H.pylori ( ATCC26695 ) or from the split products of genetically engineered bacteria (pQE30-VacA-E.coli M15) expressing recombinant VacA.The VacA protein obtained was acidified and then incubated with AGS cells for 24 h at different final concentrations of 5 and 10 ng/ml before the vacuolar change and apoptosis of AGS cells were detected via microscopy and flow cytometry assay , respectively .Results H.pylori-secreted VacA and recombi-nant VacA were successfully separated and purified .The H.pylori-secreted VacA significantly induced the vacuolar change and apoptosis of AGS cells (P<0.01) while the recombinant VacA did not.Conclusion H.pylori-secreted VacA protein can effectively induce cell vacuolar change and apoptosis, but recombinant VacA can not, suggesting that the purified VacA protein secreted by H.pylori can be used to explore VacA-induced pathogenesis.

13.
Chongqing Medicine ; (36): 772-774,781, 2014.
Artículo en Chino | WPRIM | ID: wpr-598886

RESUMEN

Objective To evaluate the guidance value of endoscopic ultrasonography (EUS) and CT scan in preoperative clinical staging for diagnosis and treatment of esophageal cancer .Methods 68 patients with esophageal cancer were randomly divided into EUS group and CT group using a random numbers table(34 cases in each group) .Patients in EUS group were examined by EUS , patients in CT group were examined by CT scan ,and staged according to the TNM (2003) staging system ,and were compared with surgical pathologic findings .Results The accuracy rates of T staging by EUS were 0(0/2) for Tis ,75 .0% (3/4) for T1 ,75 .0% (6/8) for T2 ,86 .7% (13/15) for T3 ,80 .0% (4/5) for T4 ,and the totle accuracy rate was 76 .5% (26/34) for T ;those of N staging were 71 .4% (5/7) for N0 ,75 .0% (9/12) for N1 ,0(0/11) for N2 ,0(0/4) for N3 ,and the totle accuracy rate was 41 .2% (14/34) for N .The accuracy rate of T staging by CT scan were 0(0/1) for Tis ,33 .3% (2/6) for T1 ,28 .6% (2/7) for T2 ,78 .6% (11/14) for T3 ,83 .3% (5/6) for T4 and the totle accuracy rate was 58 .8% (20/34) for T ,the difference was statistically significant com-pared with the EUS group(P<0 .05);those of N staging were 77 .8% (7/9) for N0 ,76 .9% (10/13) for N1 ,66 .7% (4/6) for N2 , 50 .0% (3/6) for N3 and the totle accuracy rate was 70 .6% (24/34) for N ,the difference was statistically significant compared with the EUS group (P<0 .05) .Conclusion The accuracy rate of EUS are higher for diagnosis in esophageal cancer and preoperative T staging .The accuracy rate of CT scan are higher for the preoperative N staging .EUS combined with CT scan has great significance for choosing ideal therapy plan for esophageal cancer ,and for estimating prognosis of esophageal cancer .

14.
Artículo en Chino | WPRIM | ID: wpr-557201

RESUMEN

Objective To explore the effects of celecoxib, a selective COX-2 inhibitor, on inducing the apoptosis of gastric cancer cells, and to elucidate the concerning mechanisms. Methods Cell viability was measured by MTT assay. Flow cytometry (FCM) was employed to assay apoptosis, mitochondrial membrane potential and intracellular free Ca 2+. Results After being exposed to celecoxib (25, 50, 100 and 200?mol/L) for 4, 8, 12 and 24h, the proliferation of SGC-7901 cells was strongly inhibited in a dose-time dependent manner. The apoptosis induced by celecoxib was accompanied with the attenuation of mitochondrial membrane potential and the elevation of intracellular free Ca 2+ concentration, suggesting the importance of mitochondria in the apoptotic pathway. Conclusion The mitochondrial pathway may be involved in the apoptosis of gastric cancer SGC-7901 cells induced by celecoxib.

15.
Artículo en Chino | WPRIM | ID: wpr-678638

RESUMEN

Objective Using a model of H.pylori infected Mongolian gerbil , we observed the effect of H.pylori and N methyl N’ nitro N nitrosoguanidine (MNNG) on gastric mucosa, in an attempt to clarify the potential role of vitamin C in the prevention of gastric carcinoma. Methods A total of 160 Mongolian gerbils , eight week old, were randomly divided into five groups(each 32 animals): Group A, infected with H.pylori ; Group B, infected with H.pylori followed by MNNG administration; Group C, received MNNG without H.pylori infection; Group D, infected with H pylori followed by administration of MNNG and vitamin C; Group E as control. Eight animals from each group were killed at 12, 24, 36, 48 weeks, and histopathological changes in their stomachs were examined for chronic gastritis, intestinal metaplasia, atypical hyperplasia and adenoma. Results The incidences of intestinal metaplasia and dysplasia in groups A and B were significantly higher than those in the other groups( P

16.
Artículo en Chino | WPRIM | ID: wpr-575393

RESUMEN

Objective To evaluate the role of mitochondrial pathway in the apoptosis of gastric epithelial cells induced by H. pylori in Mongolian gerbils. Methods A total of 48 Mongolian gerbils were randomly divided into H. pylori infection and without H. pylori infection groups. Eight animals from each group were killed at 1, 3 and 6 months, and histopathological changes in their stomachs were examined. A flow cytometry was used to measure apoptosis, mitochondrial membrane potential and intracellular free Ca2+ . Results The incidences of intestinal metaplasia and dysplasia in the gastric mucosa with H. pylori infection were significantly higher than those without H. pylori infection (P

17.
Artículo en Chino | WPRIM | ID: wpr-565211

RESUMEN

Objective To evaluate the role of mitochondrial pathway in apoptosis of gastric cancer cell line SGC-7901 induced by Helicobacter pylori(H.pylori).MethodsApoptosis was evaluated in SGC-7901 cells by flow cytometry.RT-PCR and Western blotting were used to measure the expressions of genes and proteins associated with mitochondrial pathway.Effect of caspase inhibitors on apoptosis induced by H.pylori strain NCTC11637 was investigated.ResultsNCTC11637 directly induced apoptosis in SGC-7901 cells.Apoptotic rate was 6.30%,11.57%,8.63% and 7.22% respectively at 6,12,24 and 48 h after coculture with H.pylori.H.pylori upregulated the expression of Bax,and induced a time-dependent activation of caspase-9 and-3.Apoptosis was inhibited significantly by pre-incubation with the inhibitors of caspase-9 and-3.Caspase-8 inhibitor reduced H.pylori-induced apoptosis by 20%.ConclusionH.pylori infection upregulates the expressions of Bax mRNA and protein in gastric cancer cell line SGC-7901,and induces activation of caspase-9 and-3.Mitochondrial pathway may be the major one in H.pylori-induced apoptosis in SGC-7901.

18.
Artículo en Chino | WPRIM | ID: wpr-558128

RESUMEN

Objective To study the effects of concentrated H.pylori culture supernatant(CHCS) on the expressions of COXⅠ mRNA and protein in gastric carcinoma cells,and explore the potential role of H.pylori in the gastric carcinogenesis.Methods After SGC7901 cells were treated by 6 ?l/ml CHCS for 4 h,8 h,12 h respectively,the expression of COXⅠmRNA and protein was detected by RT-PCR and Western blotting.Results The expression of COXⅠmRNA decreased gradually after exposure to CHCS for 4 h.Especially after 8 h,the expression decreased significantly.When treated with CHCS for 12 h,the expression continued to decrease(P

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