BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

Objective:To explore the correlation between the dynamic changes of early immune cells in acute respiratory dis-tress syndrome(ARDS)caused by multiple injuries and lung infection.Methods:Multiple injury patients with ARDS(235 cases)ad-mitted to the First Affiliated Hospital of Hunan University of Chinese Medicine from October 2017 to February 2023 were selected as the research subjects and included them in the training set;according to simple clinical pulmonary infection scores(sCPIS),they were divided into a pulmonary infection group(94 cases,>6 points)and an uninfected group(141 cases,≤6 points).Another multi-ple injury patients with ARDS(78 cases)were selected to be included in the validation set to verify the effectiveness of the prediction model.Dynamic detection of lymphocytes were used flow cytometry.Compared and analyzed the clinical data of two groups of patients.Constructed a joint model and used Cox regression to analyze the relationship.Multi factor Logistic regression analysis of risk factors,construction of a simple risk scoring model and evaluation.Results:As the patient progresses,CD4+and CD8+first decrease and then increased,and the lowest stage was 3～15 d after onset;CD19+was gradually increasing;CD16+gradually decreased and fluctuated within a certain range.The joint model showed that for every 1 piece/μl longitudinal decrease in CD4+,CD8+,CD19+,and CD16+,the risk of pulmonary infection increased by 5.6%,4.1%,3.4% and 1.3%,respectively(P<0.05).Injury severity score(ISS),chest inju-ry as the main factor,emergency surgery,acutephysiology and chronic health evaluation Ⅱ(APACHE Ⅱ),broncho-alveolar lavage fluid(BALF)sTREM-1 level,and CD4+,CD8+,and CD19+level on the 15th day after onset all were independent influencing factors for the occurrence of pulmonary infection(P<0.05).The score of the simple risk scoring model is 0～36.7 points,which could be divid-ed into three risk levels:low(<16 points),medium(16～22 points),and high risk(>22 points);there was no significant difference in the incidence of pulmonary infection between the two episodes of patients(P>0.05).The evaluation results showed that the predic-tive model has good discrimination.Conclusion:The fluctuation of immune cells will increase the risk of pulmonary infection in pa-tients with multiple injuries ARDS;Baseline CD4+,CD8+,and CD19+levels are independent influencing factors for the occurrence of pulmonary infection;controlling high-level immune cells and maintaining stability is crucial for improving prognosis.

Dilated cardiomyopathy(DCM)has a concealed onset with left or even whole heart enlargement as the main imaging manifestation.It is a common primary disease of heart failure and arrhythmia.With the continuous deepening of research in recent years,the intrinsic molecular mechanism of regulatory cell death(RCD)has gradually become clear.Researchers have found that the RCD mode plays a very important role in the occurrence and development of DCM.At present,the RCD modes involved in DCM mainly include apoptosis,necrotic apoptosis,pyroptosis,iron death,autophagy,and cuproptosis,and a certain correlation exists among them,which interact and regulate each other.This article provides an overview of the current research status on the mechanisms of the six RCD modes involved in DCM to provide a reference for future basic research and clinical applications.

Objective To evaluate and compare the maturity of autografts and allografts as well as the postoperative clinical outcomes 10 years after anterior cruciate ligament reconstruction(ACLR).Methods A retrospective analysis was conducted on 64 patients who underwent anterior cruciate liga-ment reconstruction,with an average follow-up period of about 10 years.Autografts were used in 36 cases(56.2%),and allografts in 28 cases(43.8%).Both groups were recorded the knee Lysholm scores,IKDC subjective scores,and stability tests results(KT-1000 side-to-side difference and Lach-man test).Moreover,graft maturity was assessed using the knee magnetic resonance imaging(MRI),and the Signal-to-Noise Quotient(SNQ)for both types of grafts was measured.Results No significant differences were observed between the autograft and allograft groups in the average follow-up time(10.1±2.1 and 10.5±1.8 years)(P=0.376),the SNQ value(24.1±8.8 and 23.2±8.7)(P= 0.652),the Lysholm score(90±10.3 and 89.4±8.9)(P=0.805)and the anterior joint stability dur-ing follow-up(P=0.923).Moreover,the average IKDC score and incidence of abnormal tension of the ligament measured by KT1000 of the autograft group were higher than the allograft group[(84.5±8.3)vs.(80.4±7.8),P=0.075;14.3%vs.8.3%,P=0.724].Meanwhile,ACL re-tear occurred to two cas-es in the autograft group(5.6%)and the allograft group(7.1%),respectively,showing no significant dif-ference(P=0.795).Conclusion Ten years after ACLR,no significant differences are found in graft ma-turity,clinical outcomes,or joint stability between patients using autografts and allografts.Moreover,the rate of graft re-tear is comparable between the two groups.

Objective To investigate the mechanism of miR-223 regulation of Nod-like receptor protein 3(NLRP3)on myocar-dial fibrosis in rats with heart failure(HE).Methods A total of fifty-four adult Wistar rats were selected to establish rat model of con-gestive HF by abdominal aortic coarctation method,and they were divided into control group,HF group,and HF+miR-223 overexpres-sion according to random number table method,with 18 rats in each group.MiR-223mimics was injected into the tail vein of HF+miR-223 overexpression group,after transfection was successful for 72h,cardiac function related indexes of rats in each group were de-tected by animal heart color ultrasound:interventricular septal thickness at end-diastole(IVSd),left ventricular posterior wall thickness at end-diastolic(LVPWd),left ventricular end-diastolic diameter(LVEDd),left ventricular end systolic diameter(LVED)and left ventricular ejectfraction(LVEF).The heart/body ratio,lung/body ratio,liver/body ratio were calculated and measured;the expression levels of miRNA-223,NLRP3,interleukin-1β(IL-1 β),tumor necrosis factor-α(TNF-α),Collagen-3,Collagen-1,Bax,and Bcl-2 in myocardial tissue of rats in each group.Results The cardiac function of the HE group was worse than that of the control group,and the expressions of NLRP3,IL-1β,TNF-α,Collagen-1,Collagen-3 and Bax were higher than those of the control group,while the expressions of miR-223 and Bcl-2 were lower than those of the control group(P＜0.05),and the degree of myocardi-al interstitial fibrosis was significantly aggravated.The cardiac function of HF+miR-223 overexpression group was better than that of the HE group,the expressions of NLRP3,IL-1 β,TNF-α,Collagen-1,Collagen-3 and Bax were lower than those of the HE group,the expressions of miR-223 and Bcl-2 were higher than those of the HE group,and the degree of myocardial interstitial fibrosis was signifi-cantly alleviated.Conclusion MiR-223 can inhibit the expression of Collagen-1 and Collagen-3 by acting on its target NLRP3,and play an important role in the occurrence and development of myocardial fibrosis in HE.

Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.