BACKGROUND:It is reported that bone marrow mesenchymal stem cell(BMSC)transplantation might be a promising treatment for liver fibrosis.But the mechanism is still unclear.OBJECTIVE:To observe the hepatic stellate cells apoptosis induced by BMSC transplantation,and to study the mechanism of BMSC in treating hepatic fibrosis in vivo.METHODS:CCl_4 subcutaneous injection was performed to induce rat liver fibrosis.After 8 weeks of CCU injection,20 rats which underwent successful model establishment were randomly divided into experimental group and control group,10 in each group.The experimental group received MSC transplantation via tail vein injection,and the control group were given DMEM instead.The rats were killed and the livers were harvested at three time point,the day of MSC transplantation,3 days after transplantation,and 7 days after transplantation.The hydroxyproline content was detected by HE and Masson staining,and the expression changes of α-smooth muscle actin(α-SMA)proteins were determined using immunohistochemistry.The apoptosis of hepatic stellate cells were determined by α-SMA and TUNEL(terminal dUTP nick-end labeling)dual-staining.RESULTS AND CONCLUSION:After 8 weeks of CCU injection,the hydroxyproline content increased and histology indicated progress of liver fibrosis.At 7 days after MSC transplantation,the hydroxyproline in the liver was decreased,and the liver fibrosis was alleviated in the experimental group but aggravated in the control group.Immunohistochemistry indicated that α-SMA positive cells were increased at 8 weeks after CCU injection.At day 7 after transplantation,α-SMA positive cells in the experimental group were significantly less than control group(P ＜ 0.05).At 3 days after transplantation,the hepatic stellate cells apoptosis in the experimental group was significantly aggravated compared with control group(P ＜ 0.05).This suggested that MSC transplant was an effective treatment for liver fibrosis.MSC inducing hepatic stellate cells apoptosis may be one of the mechanisms.

Objective:To collect the clinical materials of primary liver cancer patients treated by gamma knife and analyze the treatment methods as well as short-term efficacy,and to provide a reference for the clinical treatment of primary liver cancer patients.Methods:A total of 633 patients with inoperable primary liver cancer were treated by body gamma knife.According to the TNM staging method of Union for International Cancer Control(UICC), there were 351 cases with clear TNM staging.Among them, there were 251 cases (71.5%) at T3 stage and 57 cases(16.2%) at T4 stage.The prescription dose of 200-600 cGy each time to the 40%-85% dose line covering the planned target volume(PTV), this program was performed 5 times per week, and the number of treatment ranged from 2 to 13.The biochemical and imaging changes were observed 2-3 months after treatment to evaluate the short-term efficacy.Results:During the treatment, 229(36.2%)patients had adverse reactions,100 (15.8%) patients appeared the reduced white blood cells, and 137 (21.6%) patients appeared the reduced platelets.On discharge from the hospital, 601 patients were improved, 22 patients had no obvious change, 5 cases were worse, and 5 cases died.The proportion of improved patients who received the cumulative dose between 3 000 cGy to 4 000 cGy was higher than those who received the cumulative dose less than 3 000 cGy(P<0.05).After treatment, the curative effects were evaluated in 45 patients during two and three months, including PR 77.8%(35/45) and SD 22.2%(10/45), and the total effective rate was 77.8%(35/45).No statistical differences in effective rates were found between different tumor diameter, single dose, and cumulative dose groups(P>0.05).Conclusion:The proportion of adverse reactions in the primary liver cancer patients treated with body gamma knife is relatively low and the short-term efficacy is ideal.Body gamma knife treatment is a safe and effective treatment method for the primary liver cancer patients.

Objective The aim of this study was to explore the inhibitory effect of alcohol extracts of Narcissus bulb on melanogenesis in zebrafish embryos.Methods Zebrafish embryos were exposed to different concentrations of alcohol extracts of Narcissus (0, 50, 100, 200, and 500 μg/mL), and then the formation of melanin was observed.Furthermore, we measured the enzyme activity of tyrosinase (TYR), which plays a pivotal role in melanogenesis.Meanwhile, the spatial and temporal pattern of melanin-specific marker genes were detected.Arbutin (Ar) was used as a positive control in all these experiments.Results The treatment of alcohol extracts of Narcissus bulb inhibited melanogenesis in the zebrafish embryos in a dose-dependent manner.Furthermore, the mRNA expression levels of melanin-related genes such as tyrosinase (TYR), silver (SILV) and Mitfa were significantly reduced after treatment with different concentrations of Narcissus extracts by in-situ and semi-quantitative PCR.Finally, the enzyme activity of tyrosinase was also gradually decreased with increasing concentrations of the alcohol extracts.Conclusions Narcissus alcohol extracts can effectively inhibit the production of melanin in zebrafish embryos.This study provides potential evidence and approaches for the screening of natural whitening compounds using zebrafish models.

Objective To evaluate the clinical efficacy and safety of stereotactic radiotherapy (SRT) combined with bevacizumab for brain metastases in patients with lung adenocarcinoma.MethodsThe clinical data of 95 patients with brain metastases of lung adenocarcinoma were retrospectively analyzed, including 36 patients treated with SRT and bevacizumab (bevacizumab group) and 59 patients treated with SRT, corticosteroids, and mannitol (traditional drug group).The tumor response rate, peritumoral edema control rate, improvement in Karnofsky Performance Scale (KPS) score, and adverse reactions were analyzed.Results Compared with the traditional drug group, the bevacizumab group had significantly higher tumor response rate (P=0.033) and peritumoral edema control rate (P=0.000) at 1-4 weeks after treatment, as well as an obvious improvement in KPS score and reduced doses of corticosteroids and mannitol.In addition, the adverse reactions in the bevacizumab group were mild and controllable.Conclusions SRT combined with bevacizumab for brain metastases in patients with lung adenocarcinoma can achieve higher short-term tumor response rate and peritumoral edema control rate and improve patients' quality of life.

Objective The aim of this study is to explore the hypoglycemic effect of active components of Anoectochilus roxburghii on zebrafish models. Methods Anoectochilus roxburghii components were extracted and separated into three groups: the alcohol extraction group, macromolecular polysaccharide group (≥ 5 ×103) and small molecular polysaccharide group (＜5×103). Zebrafish embryos were exposed to 2% glucose solution (2% Glu) at 24 h to imitate acute hyperglycemia phenotype, and then treated with the three Anoectochilus roxburghii components. Based on this high-glucose model, the zebrafish embryos at 72 h were collected to detect the whole tissue glucose value. Furthermore, semi-quantitative PCR and whole mount in situ hybridization were performed to detect the expression of mRNA levels of glycometabolism-related genes. Results An acute diabetic zebrafish model was induced by high glucose stress. In this model, some key factors during glycometabolism such as insulin, pck-1 and pdx-1 were significantly affected, while the alcohol extracts of Anoectochilus roxburghii obviously reversed these abnormalities induced by high glucose stress, even to normal levels. Conclusions The alcohol extracts of Anoectochilus roxburghii has obvious hypoglycemic effect on diabetic zebrafish model. Our result suggest that Anoectochilus roxburghii has a potential application in the hypoglycemic drug screening.

Objective:To develop a simple, practical and repeatable ultrasound method to locate the muscle at the trigger point of female myofascial pelvic pain(MPP), which can provide imaging reference for clinical precision treatment.Methods:A total of 113 patients with suspected MPP who came to the Women′s Hospital School of Medicine Zhejiang University from September 1, 2021 to April 20, 2023 were prospectively selected. The gynecologist performed internal examination with index finger on some pelvic floor muscles (puborectalis, pubococcygeus, iliococcygeus, coccygeus) and pelvic wall muscles (piriformis and obturator internus) respectively, searched for the muscles where the pain trigger point was located, and scored the pain by referring to visual analogue scale (VAS) and numerical rating scale (NRS), and then referred the patients to the ultrasound department. The ultrasound doctor used transvaginal ultrasound to display the above muscle groups in real time for observation and appropriate pressure. The muscle where the painful trigger point was located was found through tenderness and the pain score was performed. The two scores were compared for consistency and difference analysis.Results:The trigger point was clear and of good reproducibility. For the location and score of pain trigger points located in bilateral puborectalis, pubococcygeus and coccygeus, there was a strong consistency between the tenderness guided by vaginal ultrasound probe and clinical palpation (the consistency rate was ≥70%), and there was no significant difference in the pain scores of the trigger points located in the puborectalis muscle and coccygeal muscle between the two methods ( P>0.05), and there was statistically significant difference in the pain scores of the trigger points located in the other pelvic floor and pelvic wall muscles (all P<0.05). At the same time, ultrasonic examination made up for the deficiency of clinical palpation in the evaluation of piriformis muscle. Conclusions:The present method for finding the trigger point of MPP guided by the ultrasound probe is a new non-invasive, safe, simple and practical imaging method, which can provide a new imaging reference for the clinical diagnosis of MPP and the formulation of treatment strategies.

ObjectiveTo explore the clinical characteristics of neurobrucellosis in Kashi， Xinjiang Uygur Autonomous Region， thus improve the diagnosis and treatment. MethodsA retrospective analysis was conducted on the clinical data of 18 cases of neurobrucellosis who were admitted to the First People's Hospital of Kashi Prefecture between December 2019 and January 2024. ResultsThe study included 9 males and 9 females， with a median age of 36 years （range： 17-54.5）. A clear epidemiological history was found in all the 18 brucllosis patients， 12 of whom presented with meningoencephalitis， 5 meningitis， and 1 encephalitis. Two comorbided with spinal meningitis， 2 osteoarthritis and 1 epididymitis. Most frequently reported clinical symptoms were headache， fever and fatigue. The prevalence rates of brucellosis by rose bengal plate agglutination test （RBPT） and serum agglutination test （SAT） were 11/12 and 8/9， respectively. Two of 10 patients had positive blood cultures， four of 16 had positive cerebrospinal fluid （CSF） cultures and five of five were detected to be positive by next-generation sequencing （NGS） for pathogens in CSF. CSF showed exudative changes and elevated number of leukocytes， with predominance of single nucleated cells. All patients were treated with the combined use of two to four from the drugs like doxycycline， rifampicin， ceftriaxone， cefixime， minocycline， levofloxacin and sulfanilamide. Most patients had a favorable prognosis. ConclusionsNeurobrucellosis should be considered in all patients with central nervous system manifestations from endemic areas. If there are exudative changes in CSF， differential diagnoses can be made by serological testing， blood culture， CSF culture and NGS. NGS could significantly increase the accuracy for neurobrucellosis diagnosis.