Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Multimorbidity has emerged as a critical global public health challenge, necessitating effective management strategies. In Heilongjiang Province, a cold north region in China with a high prevalence of multimorbidity, healthcare disparities, uneven resource distribution, and inadequate chronic disease control remain pressing issues. Driven by national policies on family physician contracting and regional demands for chronic disease management, this study established a "hospital-community general practitioner co-management" model utilizing a mobile-based digital platform. This model integrates hospital-based general practitioners into primary care teams to optimize resource allocation and enhance multimorbidity management. The initiative aims to explore pathways for improving healthcare system reform and strengthening the chronic disease prevention framework in the region.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

Multi-disciplinary team (MDT) is a widely recommended model of tumor diagnosis and treatment in modern medicine.Against the backdrop of the aging population,increasing cancer incidence rates,and the growing complexity of cancer cases in China.MDT has become a key focus in the innovative development of high-quality medical services in public hospitals.Leveraging its interdisciplinary collaboration advantages,MDT helps address the challenges presented by disease progression at various stages,thereby meeting the personalized,one-stop diagnos-tic and treatment needs of patients.It adopts a literature review approach and selects the United Kingdom as a repre-sentative case,given its early and extensive promotion of MDT at the national level and accumulated practical experi-ence.The aim is to review the development process,the organizational management,the pricing strategy,and pa-tient-centered cancer MDT practices in the UK.Building on this,a series of policy recommendations are proposed in light of the current status of cancer MDT operations in China.These recommendations include clarifying the content and implementation entities of cancer MDT services,refining MDT organizational management and quality assess-ment systems,exploring scientifically appropriate MDT pricing methods,piloting the patient agent system,ad-hering to the concept of"shared decision-making",so as to optimize the MDT system design from multi-dimen-sional perspectives to improve the quality of MDT services and benefit more patients.

Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.

Objective:To investigate the application effect of production-oriented approach (POA) for consulting ability teaching in general practice standardized residency training.Methods:Eighteen third-year general practice residents in the Second Affiliated Hospital of Harbin Medical University received a special training course on the consulting ability based on POA with the situational simulation teaching from September 2021 to March 2022. The consulting ability of residents was evaluated with Objective Structured Clinical Examination (OSCE) and Leichester Assessment Package (LAP) before and after the training, and the results were compared. Meanwhile, a questionnaire survey and semi-structured interviews were conducted to assess residents′ satisfaction with the course.Results:All 18 resident trainees (11 females and 7 males) aged 25 to 34 (27.3±2.4) years successfully completed the training. Both OSCE scores and LAP scores after the training were significantly higher than those before training (66.25±5.84 vs. 44.44±12.80, t=8.46, P<0.001; 65.78±7.05 vs. 38.33±14.2, t=1.47, P<0.001, respectively). The ability of medical history collection, physical examination, patient management, problem solving, doctor-patient relationship, preventive care and medical record writing were all significantly improved after the training compared with those before training ( t=2.464, 4.278, 8.997, 2.385, 10.35, 5.212, 7.578, all P<0.05). The questionnaire survey showed that all the 18 residents were satisfied with the reasonableness of the teaching content, the class time arrangement, the teaching progress arrangement and the instructors. In the dimension of training effectiveness, 18 participants all believed that the course was helpful to improve their humanistic quality and confidence in reception. In terms of self-promotion, all respondents believed that this course was able to promote their reflection ability and stimulate their learning interest. By coding and analyzing the contents of the semi-structured interviews with the residents, nine main themes were constructed, namely course deficiencies, course characteristics, course advantages, course suggestions, trainees′ deficiencies, trainees′ gains, trainees′ goals, previous teaching deficiencies, and instructor′s role. The results showed that all residents had a high degree of satisfaction with the course, and they thought the course was vivid and interesting and it is able to mobilize the enthusiasm of learning, promote learner to reflect. The residents also suggested to increase the teaching hours and to enrich teaching cases. Conclusion:The consulting ability training of general practice based on POA can effectively improve consulting ability, stimulate learning interest and improve independent learning ability of residents, which gains recognition from both faculty and trainees.

Objective To explore the efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5％(37/40)and 72.5％(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P＜0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P＞0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P＜0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5％(7/40)and 12.5％(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.