Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

The pharmacy of Y anqing Winter （Paralympic）Olympic Village Polyclinic of 2022 Beijing Winter （Paralympic） Olympic Games will be comprehensively managed from five aspects of man ，machine，material，method and environment by adopting the 4M1E management method of quality management tool . In terms of man ，constantly enhanced training and daily health monitoring have been insisted ；in terms of machine ，drug information entry and drug information management have been improved and maintained ；in terms of drugs ，on the basis of drug management ，the management of drugs banned by the World Anti -Doping Agency，class Ⅱ psychotropic drugs and narcotic drugs have been strengthened ；in terms of regulations and environment ，strict pharmacy workflow and management system have been established ，and epidemic prevention closed -loop management requirements have been strictly implemented . From the pre -opening of Yanqing Winter （Paralympic）Olympic Village on January 23，2022 to the official closing of the Village on March 16，2022，the clinic pharmacy dispensed a total of 156 prescriptions（105 prescriptions during the Winter Olympic Games ，51 prescriptions during the Winter Paralympic Games ），including 18 prescriptions from the National （Regional） Olympic Committee and the National （Regional） Paralympic Games team doctors ，2 prescriptions containing stimulants that do not need to be exempted from treatment，1 prescription for narcotics ，and 37 prescriptions for athletes（23.7%）. Ibuprofen tablets ，Diclofenac diethylamine emulsion，Loratadine tablets and other drugs are widely used . The application of 4M1E management method enables the clinic pharmacy to provide perfect and high -quality pharmaceutical services for large -scale events while doing well in epidemic prevention and control .

OBJECTIVE: To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance. METHODS: The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. RESULTS: Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05). CONCLUSION FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
Adenocarcinoma of Lung/metabolism* ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/metabolism* ; Neoplasm Proteins/genetics* ; Prognosis ; Proteins

Objective:To investigate the clinical effect of Jiedu Limai decoction in septic patients with syndrome of heat-toxin exuberance.Methods:A prospective randomized controlled trial was conducted. From March 2019 to April 2020, septic patients with syndrome of heat-toxin exuberance admitted to intensive care unit (ICU) of Shanghai General Hospital and Songjiang Branch of Shanghai General Hospital were enrolled as the research objects, and they were divided into routine treatment group and Jiedu Limai decoction group by the random number table method. Patients in both groups were given standard treatment in accordance with the guidelines, and patients in the Jiedu Limai decoction group were given Jiedu Limai decoction in addition to the standard treatment, once a day for 14 days. The 28-day survival of patients of the two groups were recorded, the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, coagulation indexes, infection indexes, inflammatory cytokines and organ function indicators before treatment and 7 days after treatment in both groups were recorded, and the prognosis of the two groups were recorded.Results:A total of 259 patients with infection or clinical diagnosis of infection admitted during the experimental observation period were included, and those who did not meet the Sepsis-3 diagnostic criteria, more than 80 years old or less than 18 years old, with multiple tumor metastases, autoimmune system diseases, with length of ICU stay less than 24 hours, with acute active gastrointestinal bleeding and with incomplete data were excluded. One hundred patients were finally enrolled, with 50 patients in the routine treatment group and 50 patients in the Jiedu Limai decoction group. There were no statistically significant differences in coagulation indexes, infection indicators, inflammatory cytokines and organ function indicators before treatment between the two groups. After 7 days of treatment, the coagulation indexes, infection biomarkers and inflammatory cytokines in the Jiedu Limai decoction group were significantly lower than those in the routine treatment group [D-dimer (mg/L): 2.2 (1.8, 8.5) vs. 4.0 (1.5, 8.7), fibrinogen (Fib, g/L): 3.7 (3.4, 4.3) vs. 4.2 (3.7, 4.3), fibrinogen degradation product (FDP, mg/L): 7.2 (5.4, 10.2) vs. 13.2 (9.2, 15.2), procalcitonin (PCT, μg/L): 0.4 (0.2, 2.9) vs. 0.5 (0.2, 0.9), C-reactive protein (CRP, mg/L): 50.1 (9.5, 116.0) vs. 75.1 (23.5, 115.2), interleukin-6 (IL-6, ng/L): 31.6 (21.6, 81.0) vs. 44.1 (14.0, 71.3), all P < 0.05], and the levels of B-type brain natriuretic peptide (BNP) and kidney injury molecule-1 (KIM-1) were significantly lowered [BNP (ng/L): 261.1 (87.5, 360.3) vs. 347.3 (128.8, 439.4), KIM-1 (μg/L): 0.86 (0.01, 1.40) vs. 1.24 (1.05, 1.57), both P < 0.05]. Compared with the routine treatment group, the number of new organ failure in the Jiedu Limai decoction group was decreased (30.0% vs. 50.0%, P < 0.05). Although there was no significant difference in 28-day mortality between the two groups ( P > 0.05), the 28-day mortality in the Jiedu Limai decoction group was lower than that in the routine treatment group (18.0% vs. 24.0%). Conclusion:Combining Jiedu Limai decoction to the sepsis guideline in treating syndrome of heat-toxin exuberance can effectively improve patients' coagulation function, the situation of heart and renal injury, reduce the level of inflammatory cytokines, and fewer people develop new organ failure after treatment.

OBJECTIVE: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation ; Excipients ; Printing, Three-Dimensional ; Reproducibility of Results ; Tablets

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.