OBJECTIVE: To study the effect and mechanism of Tongma Qining prescription(TQP) on improving sciatic nerve injury (SNI) in rats. METHODS: The SNI model rats were replicated by using hemostatic forceps. The model rats were randomly divided into the model group, the mecobalamine group (mecobalamine 6×10-4 g•kg-1), the high-dose group (30 g •kg-1), the medium-dose group (15 g•kg-1) and the low-dose group (7.5 g•kg-1), and the sham operation group was set(10 mice per group). After continuous intragastric administration for 6 weeks, sciatic nerve index (SFI), sensory conduction velocity (SNCV) and hemodynamic indexes were detected in each group. HE staining were employed to detect the pathological alterations of sciatic nerve tissues. Then the expression of BDNF, NGF and VEGF in sciatic nerve were detected by IHC-P, the protein expression of NGF and VEGF were detected by Western blot. RESULTS: Tongma Qining prescription was able to alleviate sciatic nerve tissue injury in SNI rats, significantly improved SFI and SNCV (P<0.01), observably reduced the hematocrit, plasma viscosity and value of whole blood viscosity (high shearing and low sheating)(P<0.05), and markedly upregulated the expression level of BDNF, NGF, VEGF and the protein expression level of NGF, VEGF (P<0.01). CONCLUSION: The Tongma Qining prescription can significantly improve SNI in rats. Its action mechanism may be related to improving blood rheology, promoting angiogenesis and protecting nerve cells.

Chemotherapy plays an important role in cancer treatment. However, the low water-solubility and serious side effects are still the biggest obstacles in clinic. In addition, the wide use of chemotherapeutic drugs would result in the multidrug resistance (MDR)and the single chemotherapy could not meet the demand of clinic anymore. Combination therapy by two or more drugs used in the same time, has become the best choice for cancer patients. It not only enhances the cytotoxicity of the chemotherapeutic drugs due to the synergistic effect of the drugs, but also inhibits the MDR to improve uptake and cytotoxicity of the chemotherapeutic drugs when adding MDR inhibitors. The drug delivery system can improve the water-solubility due to the good biocompatibility of biodegradable material which is the most property for drug delivery carriers. In addition, the targeting ability of the system and the controlled release of chemotherapeutic drugs can also reduce the side effects of drugs such as the cardiotoxicity of doxorubicin. The co-delivery system loading two or more chemotherapeutic drugs in the same carrier can get better cytotoxicity than the combination therapy using free drugs due to the efficient delivery of chemotherapeutic drugs to cancer cells, and are even better than the combination of single drug-loaded drug delivery systems because the chemotherapeutic drugs can get into the cancers cells in the same time. In addition, with the rapid development of gene therapy, the co-delivery of drugs and genes has also been a hot topic these days. In this paper, we focus on the preparation, characteristics and application of drug+drug and drug+gene co-delivery system, which can produce the synergistic effects or inhibit the MDR of cancer cells.

Objective: To investigate the effects of brain-derived neurotrophic factor-antisense long non-coding RNA (BDNF-AS) on proliferation and invasion of human hepatocellular carcinoma cells. Methods: The recombinant lentivirus carrying BDNF-AS gene was infected into hepatocellular carcinoma HepG2 and 97-H cells, respectively. The expression levels of BDNF-AS and BDNF mRNA were detected by reverse transcription PCR. The effects of BDNF-AS overexpression on the proliferation, apoptosis and invasion of HepG2 and 97-H cells were detected by EdU incorporation assay, Annexin V-FITC/propidium iodide (PI) double staining and Transwell chamber assay, respectively. Results: After infection with the recombinant lentivirus carrying BDNF-AS gene, the expression of BDNF-AS in hepatocellular carcinoma HepG2 and 97-H cells was significantly up-regulated (both P < 0.000 1), but the expression of BDNF mRNA in the two cells was significantly reduced (P < 0.000 1, P = 0.001). BDNF-AS overexpression had no effect on apoptosis of HepG2 and 97-H cells (both P > 0.05), but the proliferation and invasion abilities of the two cells were significantly decreased (P < 0.05, P = 0.001; both P < 0.000 1). Conclusion: BDNF-AS overexpression may play an important role in negatively regulating the growth and invasion of hepatocellular carcinoma cells.

ObjectiveTo analyze the management and treatment for patients with severe mental disorders in Chengdu from 2016 to 2020， in order to provide references for the relevant authorities to formulate policies and improving the mental health service system. MethodsData relating to 22 districts （cities） and counties in Chengdu from January 1， 2016 to December 31， 2020 were extracted from the National Information System for Severe Mental Disorders. Indicators such as reported prevalence rate， management rate， standardized management rate， medication rate， regular medication rate and stable condition rate of patients with severe mental disorders were analyzed on a yearly basis. ResultsBy the end of 2020， there were 71 899 registered cases of severe mental disorders in Chengdu， with a reported prevalence rate of 0.34%， a standardized management rate of 95.53%， and a regular medication rate of 72.50%. From 2016 to 2020， except the reported prevalence rate （χ²=269.566， P<0.01）， management rate （χ²=384.030， P<0.01）， standardized management rate （χ²=309.742， P<0.01）， medication rate （χ²=414.252， P<0.01）， regular medication rate （χ²=316.172， P<0.01） and stable condition rate （χ²=288.335， P<0.01） had linear trends of increasing with the annual increase. ConclusionFrom 2016 to 2020， the management rate， treatment rate and regular medication rate of patients with severe mental disorders have been increased year by year in Chengdu. Nevertheless， the increase in reported prevalence rate should be accompanied by strengthened management and follow-up to increase the regular medication rate to maintain the stability of patients' conditions.

Objective: To investigate the expression of miR-1269a in esophageal squamous cell carcinoma (ESCC) tissues and its effect on the malignant biological behaviors of ESCC KYSE30 cells, as well as to explore the underlying mechanism. Methods: Ninety specimens of ESCC tissues and adjacent para-cancerous tissues were obtained from patients underwent surgery in Fourth Hospital, Hebei Medical University. In addition, normal esophageal immortalized epithelial cells and esophageal cancer cell lines were also collected. The expression level of miR-1269a in above mentioned tissues and cell lines was examined by Real-time fluorescent quantitative PCR. After being transfected with miR-1269a mimics and inhibitors, the effects of miR-1269a on proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. The bioinformatics tool was used to predict the possible target genes of miR-1269a. Then the regulation effect of miR-1269a on target gene expression was validated by WB and Dual-luciferase reporter assay. After being transfected with SOX6 plasmid, the effects of SOX6 on the proliferation, migration, invasion and colony formation of KYSE30 cells were detected by MTS, Transwell and colony formation assay, respectively. At last, rescue assay was used to confirm the results. Results: The expression level of miR-1269a in ESCC tissues was significantly higher than that in adjacent para-cancerous tissues (P<0.05), and the expression level of miR-1269a in ESCC cell lines was significantly elevated compared with the normal epithelial cells (P<0.05 or P<0.01). The capacities of proliferation, invasion, migration and colony formation of KYSE30 cells in miR-1269a mimics transfection group were obviously higher than those in mimics NC group, while those abilities in miR-1269a inhibitor transfection group were significantly lower than those in inhibitor NC group (P<0.05 or P<0.01). Bioinformatics analysis showed that miR-1269a could combine with 3’UTR region at SOX6 gene; and after miR-1269a over-expression, the expression level of SOX6 and luciferase activity in KYSE30 cells were significantly reduced (P<0.05). Rescue assay showed that miR1269a over-expression could promote the proliferation, invasion and migration of KYSE 30 cells, while simultaneous transfection of SOX6 could partially reverse the promotion effect of miR-1269a mimics. Conclusion: The expression level of miR-1269a in ESCC tissues and cell lines is significantly increased, and it could enhance proliferation, migration, invasion and colony formation of KYSE30 cell line.And its mechanism may be related to the suppression of its target gene SOX6.

BackgroundRehabilitation for schizophrenia typically relies on pharmacological interventions， yet their efficacy in improving social function and quality of life remains limited. In recent years， non-pharmacological approaches have shown promise in enhancing rehabilitation outcomes. However， research on the effectiveness of psychomotor therapy specifically for young and middle-aged schizophrenic inpatients is limited. ObjectiveTo explore the effects of psychomotor therapy on the rehabilitation of young and middle-aged schizophrenic inpatients， and to provide a reference for treatment strategies. MethodsA total of 104 young and middle-aged schizophrenic inpatients who met the International Classification of Diseases，tenth edition （ICD-10） diagnostic criteria and hospitalized in the Fourth People's Hospital of Wuhu from June 2021 to June 2022 were selected. Patients were randomly divided into two groups of 52 each using random number table method. Both groups received treatment with risperidone tablets （2~4 mg/d） ， along with routine nursing care. Additionally， the research group received an extra 45~55 minutes of psychomotor therapy 2~3 times per week for 12 weeks. The control group received the same psychomotor therapy after the study. Positive and Negative Symptom Scale （PANSS）， Scales of Social-skills for Psychiatric Inpatient （SSPI） and Insight and Treatment Attitude Questionnaire （ITAQ） were used to assess the patients before the intervention and at 4^th， 8^th and 12^th week after the intervention. ResultsThe main effects of intervention at different time points for PANSS positive symptoms， negative symptoms and general psychopathology subscale scores， PANSS total score， SSPI score and ITAQ score were all statistically significant （F=33.989， 204.245， 82.817， 279.596， 26.144， 7.463， P<0.01）. Furthermore， statistically significant between-group differences were observed in PANSS negative symptoms and general psychopathology subscale scores， PANSS total score， SSPI score and ITAQ score （F=30.053， 5.306， 33.417， 33.013， 18.608， P<0.05 or 0.01）. Moreover， the interaction effect of time and group were statistically significant for PANSS positive symptoms， negative symptoms and general psychopathology subscale score， PANSS total score and SSPI score （F=3.472， 9.798， 3.843， 14.390， 20.661， P<0.05 or 0.01）. After 12 weeks of intervention， the research group exhibited statistically significantly lower PANSS total score and subscale scores compared with baseline （P<0.01）， while their SSPI total score was significantly higher than that of control group（P<0.01）. Additionally， compared with the control group， the research group had statistically significantly lower PANSS total score and subscale scores ， while their SSPI score was statistically significantly higher than those of control group（P<0.01）. ConclusionPsychomotor therapy may contribute to the improvement of the psychiatric symptoms and social function in young and middle-aged inpatients with schizophrenia， enhancing their rehabilitation outcomes. ［Funded by Health Commission Scientific Research Project of Wuhu （number， WHWJ2021y073）］

The report elaborated a case of a 52-year-old female patients with over 10 years of schizophrenia complicating 12 months of stupor. After a course of modified electroconvulsive therapy（MECT） combined with risperidone oral solution， the patient gradually became active and functionally recovered， and remained stable. This case suggests that MECT combined with risperidone may allow schizophrenia patients in a state of prolonged stupor to obtain clinical rehabilitation and effectively stabilize psychotic symptoms. The discussion is based on this case with a view to providing references for clinical treatment.

Background: Gastric cancer is a common gastrointestinal malignant tumor. MiR-21 can regulate the expression of phosphatase and tensin homologue (PTEN) protein and induce apoptosis of various tumor cells. Aims: To explore effect of miR-21 on proliferation, apoptosis and invasion of gastric cancer cells by targeting PTEN. Methods: SGC-7901 cells in logarithmic growth phase were divided into miR-21 mimic group, miR-21 inhibitor group, negative control group and blank control group. RT-PCR and Western blotting were used to detect mRNA and protein expressions of miR-21 and PTEN, respectively. The luciferase reporter gene assay was used to validate the targeted regulatory relationship between miR-21 and PTEN. Gastric cancer SGC-7901 cells were divided into blank control group, NC group, miR-21 group, PTEN group and miR-21+PTEN group. The proliferation activity was determined by CCK-8 assay, apoptosis was detected by TUNEL assay, and invasion and migration ability of cells was detected by Transwell and scratch test, respectively. The expressions of Ki-67, PCNA, ratio of cleaved caspase-3, Bcl-2, Bax, PTEN, p-PI3K/PI3K and p-Akt/Akt proteins were detected by Western blotting. A tumorigenesis model of nude mice was established to detect the effect of overexpression of miR-21 on the volume and mass of transplanted tumor. Results: MiR-21 could negatively regulate expression of PTEN. Compared with NC group, cell proliferation, invasion and migration rates were significantly increased in miR-21 group (P<0.05), apoptosis rate was significantly decreased (P<0.05), expressions of Ki-67, PCNA, ratio of Bcl-2/Bax, p-PI3K/PI3K and p-Akt/Akt proteins were significantly increased (P<0.05), expressions of PTEN and cleaved caspase-3 was significantly decreased (P<0.05). Cell proliferation, invasion and migration rates were significantly decreased in PTEN group (P<0.05), apoptosis rate was significantly increased (P<0.05), expressions of Ki-67, PCNA, ratio of Bcl-2/Bax, p-PI3K/PI3K and p-Akt/Akt proteins were significantly decreased (P<0.05), expressions of PTEN and cleaved caspase-3 were significantly increased (P<0.05). Compared with PTEN group, cell proliferation, invasion and migration rates were significantly increased in miR-21+PTEN group (P<0.05), apoptosis rate was significantly decreased (P<0.05), expressions of Ki-67, PCNA, ratio of Bcl-2/Bax, p-PI3K/PI3K and p-Akt/Akt proteins were significantly increased (P<0.05), and expressions of PTEN and cleaved caspase-3 were significantly decreased (P<0.05). Compared with the control group, overexpression of miR-21 significantly increased the volume and mass of transplanted tumor in nude mice (P<0.05). Conclusions: MiR-21 can negatively regulate PTEN expression, activate PI3K/Akt signaling pathway, promote proliferation, invasion and migration of gastric cancer cells, and inhibit cell apoptosis.

目前主要的免疫治疗包括溶瘤病毒、免疫检查点抑制剂、细胞因子、肿瘤疫苗、过继性免疫细胞等。溶瘤病毒是一种很有前景的抗肿瘤新兴制剂，通过选择性杀伤肿瘤细胞、诱导机体产生特异的抗肿瘤免疫反应来实现治疗肿瘤的目的。Talimogene laherparepvec (T-VEC)是第一个被批准用于治疗转移性恶性黑色素瘤的溶瘤病毒。免疫检查点抑制剂以其显著的临床疗效而备受瞩目。免疫检查点抑制剂在许多实体瘤中取得了很好的疗效，包括CTLA-4及其抑制剂、 PD-1及其抑制剂等。T-VEC与免疫检查点抑制剂抗癌优势互补。溶瘤病毒与联合免疫检查点抑制剂在恶性黑色素瘤的应用包括T-VEC与ipilimumab联合治疗、T-VEC与pembrolizumab联合治疗等。通过将溶瘤病毒与免疫检查点抑制剂联合能够显著延长肿瘤患者生存期。本文对两种免疫疗法联合治疗的合理性及两者联合在恶性黑色素瘤中的应用进展作一综述。

OBJECTIVE: To investigate the pharmacokinetics of matrine injection by different routes of administration. METHODS: Twenty healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intraperitoneal and intravenous administration of matrine injection at dose of 15 mg·kg-1 respectively. Blood samples (0.3-0.4 mL) were immediately collected into heparinized tubes before injection and at 0.033, 0.083, 0.167, 0.333, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after injection. Plasma sample concentrations were determined by a validated LC-MS/MS method. The pharmacokinetic parameters including AUC0-12, AUC0-∞, MRT0-12, MRT0-∞, t½, Vd, CL and ρmax were calculated. RESULTS: The main pharmacokinetic parameters for matrine after intraperitoneal and intravenous administration at dose of 15 mg·kg-1 were as follows:AUC0-12 (10 166±2 426), (12 217±2 968) ng·mL-1·h;AUC0-∞ (10 230±2 432), (12 300±3 031)- ng·mL-1·h;MRT0-12 (1.91±0.41), (2.14±0.54) h;MRT0-∞ (2.01±0.41), (2.26±0.64) h; t½(2.26±0.89), (2.60±1.25) h;Vd(4 998±2 010), (6 175±2 540) mL;CL (1 531±315.0), (1 727±475.6) mL·h-1·kg-1; ρmax (5 246±1 187), (8 503±1 101) ng·mL-1, respectively. The bioavailability of intraperitoneal administration is 83.21%. CONCLUSION: No significant differences were observed in AUC, MRT, t½ and CL values of matrine between different administrations except for ρmax and Vd.