BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98％and 89％,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1％.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.METHODS:Forty-eight children with β-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34+cells were 8.17×107/kg and 2.40×105/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade Ⅰ(n=2)and grade Ⅱ(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantation,cytomegalovirus infection and activation occurred in 5 of the 48 cases,sepsis in 12 cases,invasive fungal disease in 3 cases,stomatitis in 21 cases,hemorrhagic cystitis in 8 cases,and hepatic vein occlusion in 1 case.(4)Among 48 children,47 patients survived;1 died of severe pneumonia combined with acute heart failure 28 days after transplantation;43 survived without disease;3 had primary implantation failure,and 1 had pancytopenia after transplantation.The 5-year probabilities of overall survival and disease-free survival were 98％and 89％,respectively.The cumulative incidence of transplant-related deaths at 1 year was 2.1％.(5)The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease.

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.

Objective To develope a clinical decision support system(CDSS)on insulin titration and validate its effectiveness and safety.Methods Eighty patients with type 2 diabetes mellitus treated at the Department of Endocrinology of the First Affiliated Hospital of Xinxiang Medical University from January 2021 to July 2023,who had difficulty in achieving glycemic control on the basis of lifestyle interventions and oral hypoglycemic drug treatments,were selected for the study.The patients were divided into the observation group and the control group using a random number table,with 40 cases in each group.Patients in both groups received oral metformin extended-release tablets,subcutaneous insulin degludec before bedtime,and subcutaneous aspartate insulin injection before three meals for glycemic control.Patients in the observation group were given insulin titration using the CDSS,and patients in the control group were given insulin titration using the conventional method.The retrospective continuous glucose monitoring system was used to monitor time in range(TIR)for glucose,mean amplitude of glycemic excursion(MAGE),mean blood glucose(MBG),standard deviation of blood glucose(SDBG),and the coefficient of variation(CV)of blood glucose.Fasting blood glucose(FBG),2-hour postprandial glucose(2hPG),length of hospitalization,time to achieve standard blood glucose control,and incidence of hypoglycemia of patients were recorded before and after treatment in the two groups.Results There was no significant difference in FBG and 2hPG of patients between the two groups before treat-ment(P＞0.05).The FBG and 2hPG levels of patients in the two groups were significantly lower than those before treatment(P＜0.05).The FBG and 2hPG levels of patients in the observation group were significantly lower than those in the control group after treatment(P＜0.05).TIR of patients in the observation group was significantly higher than that in the control group,while MAGE,MBG,SDBG,and CV were significantly lower than those in the control group after treatment(P＜0.05).The length of hospitalization was 9.0(7.3,10.0)days and 11.0(8.3,12.0)days of patients in the observation group and control group,respectively;and the length of hospitalization of patients in the control group was significantly longer than that in the observation group(Z=-2.408,P＜0.05).The time required to achieve glycemic control was 6.5(5.0,8.8)days and 7.5(6.0,10.0)days of patients in the observation group and control group,respectively;and the time required to achieve glycemic control of patients in the control group was significantly longer than that in the observation group(Z=-2.019,P＜0.05).The incidence of hypoglycemia of patients in the observation group and control group was 20.0％(8/40),12.5％(5/40),respectively;there was no significant difference in the incidence of hypoglycemia between the observation group and the control group(x2=0.827,P＞0.05).Conclusion Compared with the conventional titration of insulin,the application of CDSS can provide decision support during the implementation of a basal-meal insulin regimen,which can lead to more effective glycemic control,improved glucose TIR,reduced glycemic fluctuations,shorter time required for patients to achieve glycemic control,and shorter hospital stays without increasing the risk of hypoglycemia.

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 current status of the use and management of medical devices in various primary medical and health institutions under hierarchical medical diagnosis and treatment.Methods:A stratified random cluster sampling method was used to select 450 medical personnel from 50 township and urban primary medical and health institutions of Shijiazhuang from May to August 2023 and a questionnaire network survey on the use and management of medical devices was conducted,which covered 16 items across three dimensions including the use of commonly used medical devices in primary medical institutions,maintenance and quality control management.Results:A total of 450 questionnaires were distributed and 450 valid questionnaires were collected,including 239 from township primary level medical institutions and 211 from urban primary level ones.According to the results of 211 urban primary level questionnaires,the proportions of the training and examination carried out by the medical staff of urban grass-roots medical and health institutions prior to the use of medical devices,understanding parameters of medical devices and timely detection of malfunction of medical devices were 62.6%(132/211),77.7%(164/211)and 70.1%(148/211),respectively,which were higher than those at the township primary level,the difference was statistically significant(x2=17.750,29.649,22.384,P<0.05).The proportions of urban primary medical and health institutions with maintenance system,inspection and maintenance standards,regular calibration provisions,and equipment calibration standards were 64.0%(135/211),53.6%(112/211),55.9%(118/211)and 55.0%(116/211),respectively,which were higher than those of the township primary level,the difference was statistically significant(x2=5.834,34.728,6.004,25.540,P<0.05).The difference was not statistically significant between urban primary level and township primary level in each item of quality control management(P>0.05).Conclusion:Primary medical and health institutions were required to strengthen training and assessment before medical and health personnel use medical devices;improve related system and standards for medical device maintenance;formulate quality control management system for commonly used medical devices;strengthen analysis and discussion processes after quality control,and promote continuous improvement of medical device quality management.

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.

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.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Objective To evaluate the the relationship between the mechanism underlying electroacupuncture (EA)-induced improvement of postoperative cognitive dysfunction and mitochondrion-depend-ent apoptosis in hippocampal neurons of aged rats.Methods Seventy-two healthy male Sprague-Dawley rats,aged 18 months,weighing 500-550 g,were divided into 3 groups (n =24 each) using a random number table method:control group (group C),operation group (group O) and group EA.EA was performed at Baihui and Dazhui acupoints for 30 min using disperse-dense waves,with a frequency 2/15 Hz and intensity 1 mA,once a day for 5 consecutive days in group EA.Laparotomy was performed under 3％sevoflurane anesthesia after the end of EA stimulation in O and EA groups.Morris water maze test was performed on 1 day before operation and 3 and 7 days after operation to assess the cognitive function.Rats were sacrificed after the end of Morris water maze test,brains were removed,and hippocampal tissues were obtained for detection of apoptosis rate of hippocampal neurons and expression of hippocampal caspase-3 and cytochrome c (Cyt c) by Western blot.Results Compared with group C,the escape latency was significantly prolonged after operation,the frequency of crossing the original platform was reduced,the apoptotic rate of hippocampal neurons was increased,and the expression of caspase-3 and Cyt c was up-regulated in O and A groups (P＜0.05).Compared with group O,the escape latency was significantly shortened after operation,the frequency of crossing the original platform was increased,the apoptotic rate of hippocampal neurons was decreased,and the expression of caspase-3 and Cyt c was down-regulated in EA group (P＜0.05).Conclusion The mechanism by which EA improves postoperative cognitive dysfunction may be related to inhibiting mitochondrion-dependent apoptosis in hippocampal neurons of aged rats.