OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To evaluate the diagnostic value of PSA and the f/t PSA ratio in prostate cancer screening in Chinese people.Methods:Original articles on the application of PSA and f/t PSA ratio in prostate cancer screening among Chinese population were retrieved from Pubmed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang data and VIP databases from the establishment of the database to June 2023. The literature quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2) tool. A meta-analysis was performed with Stata 15.1 software.Results:A total of 26 articles were included, encompassing 18 407 individuals, of whom 4 095 were diagnosed with prostate cancer based on biopsy and postoperative pathological examination, while the rest were patients with other prostate diseases or healthy individuals. 24 used a PSA threshold of>4.0 ng/ml as the cutoff for prostate cancer screening, the pooled sensitivity was 0.88(95% CI: 0.84-0.91), the specificity was 0.42(95% CI: 0.34-0.50), and the area under the summary receiver operating characteristic (SROC) curve (AUC) was 0.7(95% CI: 0.73-0.81). Four articles considered a PSA threshold of>10.0 ng/ml for prostate cancer screening (three of which used the above two cutoff values), the pooled sensitivity was 0.83(95% CI: 0.74-0.89), the specificity was 0.67(95% CI: 0.45-0.84), and the AUC of the SROC was 0.79(95% CI: 0.75-0.83). Eleven articles used the f/t PSA ratio as a screening tool for prostate cancer. When the f/t PSA ratio was<0.16, the pooled sensitivity was 0.82(95% CI: 0.76-0.87), the specificity was 0.76(95% CI: 0.67-0.83), and the AUC of the SROC was 0.86(95% CI: 0.83-0.89). Conclusion:In the screening for prostate cancer in China, PSA has a relatively high sensitivity, and the f/t PSA ratio has a better specificity. Combined application of the two indices is recommended.

Aim To investigate the serum levels of thrombin-antithrombin complex(TAT),tissue type plas-minogen activator-inhibitor complex(t-PAIC)and thrombomodulin(TM)in patients with intracranial atherosclerotic steno-sis(ICAS),and their correlations with the degree of stenosis.Methods A total of 196 ICAS patients(ICAS group)who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research sub-jects.Based on the degree of vascular stenosis,they were separated into three groups:mild group(n=78),moderate group(n.=64),and severe group(n=54).A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls.The serum levels of TAT,t-PAIC,and TM in each group were compared;Spearman method was applied to analyze the correlation between serum levels of TAT,t-PAIC,TM and stenosis severity in ICAS pa-tients;Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients;ROC curve was applied to analyze the predictive value of serum TAT,t-PAIC,TM and total cholesterol(TC)levels for se-vere stenosis in ICAS patients.Results Compared with the control group,the serum levels of TAT,t-PAIC,and TM were significantly increased in the ICAS group(P＜0.05);the levels of serum TAT,t-PAIC,TM,and TC in the mild,moderate,and severe groups increased accordingly(P＜0.05).Spearman analysis showed that the serum levels of TAT,t-PAIC,and TM in ICAS patients were positively correlated with the degree of stenosis(r=0.574,0.695,0.628;all P＜0.05).Multivariate Logistic regression analysis showed that TAT,t-PAIC,TM,and TC were independent risk factors for severe stenosis in ICAS patients(P＜0.05).The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT,t-PAIC,TM,and TC was 0.927,with a sensitivity of 83.33％and a specificity of 86.62％,which was superior to the independent prediction of TAT,t-PAIC,TM and TC(Zcombined detection-TAT=4.617,Zcombined deteetion-t-PAIC=4.024,Zcombined detection-TM=4.004,Zcombined detection-TC=7.078,all P=0.000).Conclusion The ser-um levels of TAT,t-PAIC,and TM in the ICAS group were significantly increased,and were positively correlated with the severity of stenosis.The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

Objective:To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma(MM)bone disease(MBD)patients with different blood separation results.Methods:A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group[119 cases,serum,colloid and red blood cell(RBC)from top to bottom of sample]and abnormal group(15 cases,serum,mixed layer of RBC and serum,colloid and RBC from top to bottom of sample)according to the results of blood separation.According to the imaging findings,MBD was classified into grade 0-4,grade 0-2 was mild,and grade 3-4 was severe.The MBD grade of patients in the two groups was analyzed.The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated.The correlation between β 2-microglobulin(MG)and bone metabolic indexes was analyzed by Pearson correlation analysis.Results:In the control group,there were 69 cases of grade 0-2 and 50 cases of grade 3-4,while in the abnormal group,there were 5 cases of grade 0-2 and 10 cases of grade 3-4,the difference was statistically significant(P＜0.05).The serum β 2-MG,β-CTX levels in abnormal group were both significantly higher than those in control group,while the levels of P1NP and osteocalcin(OC)were significantly lower(all P＜0.001).In the control group,there were 95 patients with ≥ partial response(PR)and the blood separation results were not changed,while 24 patients with＜PR and 5 of them had abnormal blood separation results.In the abnormal group,9 patients with efficacy≥PR showed normal blood separation results,while 6 patients with efficacy＜PR and 5 of them still remained abnormal blood separation results.Compared with before treatment,β-CTX and β 2-MG of patients with efficacy ≥ PR were significantly decreased but P1NP and OC increased in the control group(all P＜0.00 1),which was the same as abnoraml group(both P＜0.001,P＜0.01).There were no significant changes in the levels of all indexes in the two groups of patients with efficacy＜PR(P＞0.05).Compared with before treatment,the levels of β-CTX and β 2-MG in the control group with unchanged blood separation results were significantly decreased(both P＜0.00l),while the levels of P1NP and OC were significantly increased(P＜0.01,P＜0.001),and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change(P＞0.05);the levels of β-CTX and β 2-MG in the abnormal group transformed to normal blood separation result were significantly decreased(both P＜0.01),while the levels of P1NP and OC were significantly increased(P＜0.001,P＜0.01),and the level of each index in patients with unchanged blood separation results did not significantly change(P＞0.05).Pearson correlation analysis showed that serumβ 2-MG was positively correlated with β-CTX(r=0.709,P＜0.001),and negatively correlated with P1NP and OC(r=-0.410,r=-0.412,both P＜0.001).Conclusion:MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis,which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels,leading to more serious bone metabolic homeostasis disorder.The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition,efficacy monitoring and prognosis evaluation of MBD patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P>0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.