Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate the significance and prognostic value of integrin α5,β1 andβ2 in colorectal cancer(CRC).Methods The clinical data of 187 patients with CRC who were diagnosed in the hospital from January 2017 to January 2018 were analyzed retrospectively.The expression of integrin α5,β1and β2 in cancer tissues and adjacent tissues,and its relationship with pathological characteristics of CRC were analyzed.All patients were followed up for 5 years after operation.Postoperative recurrence and survival time were recorded.Results The positive expression rates of integrin α5,β1 and β2 in cancer tissues were higher than adjacent tissues(P＜0.05).There was no statistically significant difference in the expression levels of integrin α5,β1 and β2 in patients of different gender,patients of different age and patients with different tumor diameters(P＞0.05).The expression levels of integrin α5,β1 and β2 in patients with different differentiation degrees,patients in different TNM stages,and patients with and without lymph node metastasis were significantly different(P＜0.05).All of the 187 patients were followed up for 5 years,without any case lost to follow-up,and a total of 84 patients had recurrence.The positive expression rates of integrin α5,β1 and β2 in patients with recurrence were higher than those in patients without(P＜0.05).The average survival time and survival rate of patients with positive expression of integrin α5,β1and β2 were shorter/lower than those of patients with negative expression(P＜0.05).Conclusion The positive expression rates of integrin α5,β1and β2 in CRC patients are increased.They are closely related to differentiation degree,TNM stage and lymph node metastasis,and influence postoperative recurrence and survival time of the patients.Therefore,the above indicators can be used for prognosis.

To implement the strategy of healthy China and promote the construction of "new medicine science", it is urgent to focus on new needs and challenges to advance the reform of medical education curricula in China. Using literature research methods, we summarize the process of modern medical education curriculum reforms in the United States, and discuss the main features of the third-round reforms—introducing the concept of value-based medicine, offering health systems science courses, and promoting the curriculum system reform from the perspectives of learning time, curriculum integration, and learning methods. Based on these features, we put forward the enlightenment for the reform of medical education curricula in China.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective To explore the application of polysomnography combined with arterial spin labeling(ASL)perfusion magnetic resonance imaging in the diagnosis of insomnia.Methods Forty-two insomnia patients admitted to Department of Neurology were included as insomnia group,while 41 healthy subjects during the same period were included as control group.The two groups were assessed using sleep habits questionnaire,hospital anxiety and depression scale,polysomnography,and ASL perfusion magnetic resonance imaging.Results Compared with control group,insomnia group took significantly more time to fall asleep(P<0.05),and has shorter sleep duration(P<0.05).The differences in the levels of anxiety and depression between two groups were trivial.The total sleep time,rapid eye movement sleep duration,and non-rapid eye movement sleep stage S2-S4were shorter,while the sleep latency and non-rapid eye movement sleep stage S1were longer in insomnia group as compared with control group(all P<0.05).In insomnia group,perfusion was increased in bilateral prefrontal lobes,right temporal lobe,left parietal lobe,right thalamus,and pons(P<0.05),but decreased in bilateral insula and bilateral basal ganglia(P<0.05).Conclusion The combination of polysomnography and ASL perfusion magnetic resonance imaging enables precise quantification of sleep condition.

Objective:To explore the characteristics of anorectal motility and sensation in patients with functional anorectal pain (FAP) by high-resolution anorectal manometry (HR-ARM) .Methods:The clinical data of 81 FAP patients (FAP group) who underwent HR-ARM in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from January 1, 2020 to January 31, 2022 were retrospectively collected, and 80 healthy volunteers were recruited as healthy control group during the same period. The HR-ARM characteristics were compared between FAP group and the healthy control group, between the patients with different genders in the FAP group, the patients with different subtypes (proctalgia fugax, levator syndrome, and non-specific FAP) in the FAP group, which included anal resting pressure, anal squeeze pressure, rectal pressure during simulated defecation, anal residual pressure during simulated defecation, paradoxical contractions, initial sensation threshold, defecation threshold, defecation urgency threshold, and tolerance threshold. Visual analogue scale (VAS) was used to assess the pain level of the patients in the FAP group, and Spearman correlation analysis was used to analyze the correlation between VAS and HR-ARM characteristics. Independent sample t-test, least significant difference test, Tamhane′s T2 test, and Mann-Whitney U test were used for statistical analysis. Results:The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of the FAP group were all lower than those of the healthy control group ((59.56±24.71) mmHg (1 mmHg=0.133 kPa) vs. (81.94±15.87) mmHg, (119.04±46.94) mmHg vs.(154.62±37.95) mmHg, 59.00(40.75, 80.95) mmHg vs. 83.10(61.78, 94.30) mmHg, 70.00(55.00, 90.00) mL vs. 85.00(60.00, 110.00) mL, 105.00(87.50, 150.00) mL vs. 140.00(100.00, 180.00) mL), and the differences were all statistically significant ( t=-6.83 and -5.29, Z=-4.12, -3.12 and -2.82; all P<0.01).The rectal pressure during simulated defecation of male patients in the FAP group was higher than that of males in the healthy control group, and the defecation urgency threshold was lower than that of males in the healthy control group (42.40(29.60, 57.95) mmHg vs. 31.10(25.85, 36.80) mmHg, 80.00(62.50, 107.50) mL vs. 92.00(81.00, 140.00) mL), and the differences were statistically significant ( Z=-1.99 and -2.53, both P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of female in the healthy control group ((55.67±21.61) mmHg vs. (87.04±15.54) mmHg, (102.70±37.09) mmHg vs. (155.98±31.44) mmHg, 52.55(40.53, 67.48) mmHg vs. 83.10(61.10, 94.50) mmHg, 60.00(52.50, 81.50) mL vs. 80.00(60.00, 100.00) mL, 101.00(80.00, 128.75) mL vs. 120.00(94.00, 155.00) mL), and the differences were statistically significant ( t=-8.77 and -8.16, Z=-4.57, -2.24 and -2.14; all P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, incidence rate of paradoxical contractions, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of male patients in FAP group ((55.67±21.61) mmHg vs. (68.28±29.16) mmHg, (102.70±37.09) mmHg vs. (155.62±46.66) mmHg, 52.55(40.53, 67.48) mmHg vs. 79.00(59.55, 99.25) mmHg, 28.6%(16/56) vs. 68.0%(17/25), 44.00(35.00, 60.00) mL vs. 60.00(45.00, 70.00) mL, 60.00(52.50, 81.50) mL vs. 80.00(62.50, 107.50) mL), and the differences were statistically significant( t=2.17 and 5.47, Z=-2.96, χ2=11.10, Z=-2.93 and -2.34; all P<0.05). The anal squeeze pressure of patients with proctalgia fugax subtype was higher than that of patients with levator syndrome subtype ((140.19±56.51) mmHg vs. (80.56±30.79) mmHg), and the tolerance threshold was lower than that of patients with non-specific FAP subtype ((87.86±17.80) mL vs. (125.14±48.31) mL), and the differences were statistically significant ( t=2.35 and 2.02, both P<0.05). The results of Spearman correlation analysis showed that VAS was negatively correlated with anal resting pressure, anal squeeze pressure, and defecation urgency threshold in the patients of the FAP group ( r= -0.28, -0.23, and -0.24; all P< 0.05). Conclusion:The presence of anorectal dismotility and sensory dysfunction in FAP may be related to pelvic floor muscle abnormalities, muscle coordination disorders during defecation, and rectal hypersensitivity.

OBJECTIVE To provide reference for the clinical application and further research and development of Shenling baizhu powder. METHODS Using the methods of textual research and bibliometrics， the key information such as the composition， dose， processing and usage of Shenling baizhu powder in ancient and modern literature were systematically summarized and sorted out， and the number of publications， keywords， and other contents of modern literature were visually analyzed. RESULTS & CONCLUSIONS Shenling baizhu powder was first collected in Taiping Huimin Hejiju Fang （abbreviated “Jufang”）， the composition of core drugs and most widely used dose ratio in previous generations were the same as those in Jufang， basically focusing on powder making and being taken after mixed with liquid； the dosage was concentrated on 2-3 qian； the function and application of it had been expanded to a certain extent compared with Jufang； its clinical application had gradually extended from internal medicine to surgery， gynecology， pediatrics， ophthalmology， dermatology， etc.， covering all aspects of the disease caused by spleen deficiency in general； the composition mechanism revolved around “strengthening the spleen， replenishing qi and removing dampness”； the recommended prescription drugs were all selected from the corresponding varieties in the pharmacopoeia. Modern research mainly focuses on clinical practice， with traditional Chinese medicine or traditional Chinese and Western medicine combined with this formula as the main modified treatment for various intestinal diseases， diarrhea diseases， and lung diseases. The efficacy and application are the frontier hot spots today， and the mechanism of action has begun to be explored. The usage in the literature and the inclusion in the pharmacopoeia are inconsistent， and further research is needed.

Objective: To investigate the trends in incidence of viral hepatitis in Yuxi City, Yunnan Province from 2004 to 2022, so as to provide insights into the management of viral hepatitis. Methods: Data of viral hepatitis cases in Yuxi City from 2004 to 2022 were retrieved from the China Disease Prevention and Control Information System. The temporal, human and spatial distribution of viral hepatitis cases were analyzed using a descriptive epidemiological method, and the trends in incidence of viral hepatitis were evaluated in Yuxi City from 2004 to 2022 using annual percent change (APC) and average APC (AAPC). Results: A total of 37 430 viral hepatitis cases were reported in Yuxi City from 2004 to 2022, with an average annual incidence rate of 91.27/105, and the incidence showed a tendency towards a rise (AAPC=12.686, P<0.05). There were 29 229 cases with hepatitis B, 5 796 cases with hepatitis C, 1 451 cases with hepatitis A, 520 cases with hepatitis E and 434 cases with unclassified hepatitis reported in Yuxi City, with average annual incidence rates of 71.27/105, 14.13/105, 3.54/105, 1.27/105 and 1.06/105, respectively. The average annual incidence rates of viral hepatitis were 98.24/105 and 78.94/105 among men and women, which both appeared a tendency towards a rise (AAPC=12.415% and 12.581%, both P<0.05). The highest average annual incidence of viral hepatitis was seen among residents at age of 25 to 29 years (139.89/105), with the lowest seen among residents at ages of 0 to 4 years (11.38/105), and the average annual incidence of viral hepatitis appeared a tendency towards a rise with age (P<0.05). The highest average annual incidence of viral hepatitis was seen in Huaning County (234.24/105), with the lowest seen in Chengjiang City (26.11/105), and the average annual incidence appeared a tendency towards a rise in Xinping County from 2004 to 2022 (AAPC=21.451%, P<0.05). Conclusions The reported incidence of viral hepatitis appeared a tendency towards a rise in Yuxi City from 2004 to 2022, with hepatitis B as the main type. High incidence was seen among men and adolescents. The viral hepatitis control strategy requires to be adjusted with adaptations to high-incidence hepatitis subgroups, residents and regions.