Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Objective:To observe the clinical efficacy and effects on emotional state, anorectal physiological function, serum inflammation factors and neurotransmitters of repetitive transcranial magnetic stimulation (rTMS) on functional anorectal pain (FAP) patients, and to explore the potential therapeutic mechanisms.Methods:From September 1, 2022 to December 31, 2023, a total of 50 FAP patients who were admitted to Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine were enrolled in this study. The patients were randomly divided into the treatment group (20 cases) and the control group (20 cases) according to a random number table and relevant exclusion criteria. The treatment group received rTMS treatment and the control group received sham rTMS treatment. The Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, visual analogue scale (VAS) score, high-resolution anorectal manometry data (anal resting pressure, anal squeeze pressure, initial sensation shreshold, defecation shreshold, defecation urgency shreshold, and tolerance shreshold), and the levels of serum inflammatory factors (interleukin(IL)-4, IL-8, tumor necrosis factor-α) and 5-hydroxytryptamin(5-HT) were recorded before and after treatment. Independent sample t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:The VAS, HAMA, and HAMD scores of the treatment group after treatment were lower than those before treatment (3.85±2.23 vs. 6.85±1.98, 4.40±3.39 vs. 8.75±6.60, and 7.10±6.56 vs. 12.85±7.20), and were also lower than those of the control group after treatment(6.50±1.76, 8.20±6.65, 12.10±6.80), and the differences were statistically significant ( t=5.68, 4.72, 6.06; -4.17, -2.27, -2.37; P<0.001, <0.001, <0.001; <0.001, =0.028, and =0.023). The initial sensation shreshold, defecation shreshold, defecation urgency shreshold, and tolerance shreshold of the treatment group after treatment were higher than those before treatment(30.00(30.00, 46.00) mmHg (1 mmHg=0.133 kPa) vs. 23.00(18.50, 29.00) mmHg, 50.00(44.50, 60.00) mmHg vs. 37.00(30.75, 51.50) mmHg, (74.30±16.02) mmHg vs. (63.70±22.21) mmHg, 119.00(100.00, 148.00) mmHg vs. 98.00 (69.50, 153.00) mmHg), and the tolerance shreshold of the treatment group after treatment was higher than that of the control group after treatment(119.00 (100.00, 148.00) mmHg vs. 102.00(84.50, 111.50) mmHg), and the differences were statistically significant ( Z=–3.14 and –2.86, t=-4.02, Z=-2.84 and -2.11; P=0.002, 0.004, 0.001, 0.004, and 0.035). Additionally, the 5-HT level of the treatment group after treatment was higher than that before treatment (1 549.41 (1 320.21, 1 640.03) μg/L vs. 1 081.52(874.36, 1 626.79) μg/L), and the difference was statistically significant ( Z=-2.88, P=0.004). Conclusion:The rTMS treatment can effectively relieve the pain, anxiety and depression, improve visceral sensitivity, and influence the neurotransmitter level of brain-gut axis in FAP patients.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

Objective:To observe the clinical efficacy and effects on emotional state, anorectal physiological function, serum inflammation factors and neurotransmitters of repetitive transcranial magnetic stimulation (rTMS) on functional anorectal pain (FAP) patients, and to explore the potential therapeutic mechanisms.Methods:From September 1, 2022 to December 31, 2023, a total of 50 FAP patients who were admitted to Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine were enrolled in this study. The patients were randomly divided into the treatment group (20 cases) and the control group (20 cases) according to a random number table and relevant exclusion criteria. The treatment group received rTMS treatment and the control group received sham rTMS treatment. The Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, visual analogue scale (VAS) score, high-resolution anorectal manometry data (anal resting pressure, anal squeeze pressure, initial sensation shreshold, defecation shreshold, defecation urgency shreshold, and tolerance shreshold), and the levels of serum inflammatory factors (interleukin(IL)-4, IL-8, tumor necrosis factor-α) and 5-hydroxytryptamin(5-HT) were recorded before and after treatment. Independent sample t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:The VAS, HAMA, and HAMD scores of the treatment group after treatment were lower than those before treatment (3.85±2.23 vs. 6.85±1.98, 4.40±3.39 vs. 8.75±6.60, and 7.10±6.56 vs. 12.85±7.20), and were also lower than those of the control group after treatment(6.50±1.76, 8.20±6.65, 12.10±6.80), and the differences were statistically significant ( t=5.68, 4.72, 6.06; -4.17, -2.27, -2.37; P<0.001, <0.001, <0.001; <0.001, =0.028, and =0.023). The initial sensation shreshold, defecation shreshold, defecation urgency shreshold, and tolerance shreshold of the treatment group after treatment were higher than those before treatment(30.00(30.00, 46.00) mmHg (1 mmHg=0.133 kPa) vs. 23.00(18.50, 29.00) mmHg, 50.00(44.50, 60.00) mmHg vs. 37.00(30.75, 51.50) mmHg, (74.30±16.02) mmHg vs. (63.70±22.21) mmHg, 119.00(100.00, 148.00) mmHg vs. 98.00 (69.50, 153.00) mmHg), and the tolerance shreshold of the treatment group after treatment was higher than that of the control group after treatment(119.00 (100.00, 148.00) mmHg vs. 102.00(84.50, 111.50) mmHg), and the differences were statistically significant ( Z=–3.14 and –2.86, t=-4.02, Z=-2.84 and -2.11; P=0.002, 0.004, 0.001, 0.004, and 0.035). Additionally, the 5-HT level of the treatment group after treatment was higher than that before treatment (1 549.41 (1 320.21, 1 640.03) μg/L vs. 1 081.52(874.36, 1 626.79) μg/L), and the difference was statistically significant ( Z=-2.88, P=0.004). Conclusion:The rTMS treatment can effectively relieve the pain, anxiety and depression, improve visceral sensitivity, and influence the neurotransmitter level of brain-gut axis in FAP patients.

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.

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 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.