Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.

Objective To investigate the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSCs-Exo)on the regulation of epithelia-mesenchymal transition(EMT)in human peritoneal mesothelial cells(HPMCs)treated with glucose-based peritoneal dialysis fluid(PDF).Methods BMSCs-Exo were verified by transmission electron microscopy(TEM),nanoparticle tracking analyzer(NTA)and Western blot.Cultured HPMCs(HMrSV5)were divided into 5 groups;control group,high glucose-based PDF(1.5％,2.5％,and 4.25％)group,siNLRP3 group,siNC group and BMSCs-Exo treated group.Expression of E-cadherin,vimentin,α-smooth muscle actin(α-SMA)and NLRP3 inflammasome-related proteins were detected by Western blot.Real time RT-PCR was used to detected the expression of α-SMA,E-cadherin and TGF-β1 mRNAs in HMrSV5 cells.The concentration of TGF-β1,IL-1 β and IL-18 in the culture supernatant was determined by ELISA.Results The exosomes isolated were spherical and double-membrane vesicles with 40-150 nm in diameter,which expressed CD9,CD81,TSG101 and Alix protein.Our results showed that the level of α-SMA and vimentin were significantly up-regulated and E-cadherin(epithelial marker)was significantly decreased in HMrSV5 cells treated with high glucose PDF com-pared with the normal HMrSV5 cells.The expression of NLRP3,pro-caspase-1 and pro-IL-1β were also significantly up-regulated in HMrSV5 cells treated with high glucose PDF compared with the normal HMrSV5 cells.The level of TGF-β1,IL-1 β and IL-18 in high glucose PDF treated HMrSV5 cells culture supernatant was up-regulated in a dose dependent manner.The protein level of α-SMA was decreased and E-cadherin level was increased by an NLRP3 siRNA to inhibit the activation of NLRP3.Compared with 4.25％PDF treated cells,E-cadherin expression was up-regulated,while the expression of α-SMA and vimentin were down-regulated in BMSCs-Exo treatment cells(P＜0.05).Furthermore,the protein expression of NLRP3,pro-caspase-1 and pro-IL-1β in 4.25％PDF-treated HMrSV5 cells were significantly reduced by BMSCs-Exo.BMSCs-Exo also reduced the level of TGF-β1,IL-1 β and IL-8 in the 4.25％PDF-treated HMrSV5 cells culture supernatants(P＜0.05).Conclusions High glucose PDF-induced EMT in HPMCs might be mediated by NLRP3 inflammatory signaling pathway,which can be inhibited by BMSCs-Exo.

Objective:To analyze the clinicopathological features of solitary papillary thyroid isthmus carcinoma (SPTIC) and the therapeutic effect and prognosis of different surgical methods.Methods:A total of 161 patients with SPTIC who underwent surgical treatment in the Department of Thyroid Surgery of the First Hospital of Jilin University from Dec. 2012 to Oct. 2021 were selected. Gender, age, body mass index and pathology of the patients were collected and the clinicopathological characteristics of SPTIC were analyzed. They were divided into three groups according to different surgical methods: group A underwent isthmic excision, group B underwent extended isthmic excision, and group C underwent total thyroidectomy. There were 47 patients in group A (8 males and 39 females with an average age of 42.6±9.1 years), 50 patients in group B (11 males and 39 females with an average age of 45.3±11.3 years), and 64 patients in group C (10 males and 54 females with an average age of 46.9±11.4 years). The clinicopathological features and therapeutic effect of the three groups were compared by ANOVA, multiple local rank sum test, χ2 test or Fisher's exact probability method, and the recurrence rate and recurrence free survival (RFS) of the three groups were compared after a follow-up of 6 to 126 months. Results:Among the 161 patients with SPTIC, 132 (82.0%) were female, 130 (80.7%) were younger than 55 years old, BMI (25.1±3.6) kg/m 2, 124 (77.0%) were combined with capsule invasion. There were 53 cases (32.9%) with central lymph node metastasis (CLNM). Subgroup analysis showed that the proportion of males in patients with tumor diameter > 1 cm, the proportion of patients with BMI≥26.0 kg/m 2, the rate of capsular invasion, the rate of extrandular invasion and the rate of CLNM were higher (30.0% vs. 14.0%, P=0.023; 60.0% vs. 33.9%, P=0.004; 97.5% vs. 70.2%, P< 0.001; 42.5% vs. 9.9%, P<0.001; 50.0% vs. 27.3%, P=0.008) ; The CLNM rate was higher in male patients with BMI≥26.0 kg/m 2 and tumor diameter > 1 cm (28.3% vs. 13.0%, P=0.017; 52.8% vs. 34.3%, P=0.024; 37.7% vs. 18.5%, P=0.008). Compared with groups A and B, group C had longer hospitalization days, higher hospitalization costs, longer operation time, more postoperative drainage flow and higher incidence of postoperative hypoparathyroidism, and the differences were statistically significant (all P< 0.05). Groups A and B were similar in all aspects, with no statistical significance ( P> 0.05 for all). During the follow-up, 3 patients in both group A and B relapsed, while no patients in group C relapsed, and there were no statistically significant differences in the recurrence rate ( P=0.059) or RFS ( P=0.082) among the three groups. Conclusions:The majority of SPTIC were microcarcinomas, but the incidence of tumor combined with capsule invasion was higher, and the tumor size of more than 1 cm was more invasive (capsule invasion rate and extrathyroid invasion rate were higher). SPTIC should be treated as conservatively as possible (isthmic excision or enlarged isthmic excision) .

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

A retrospective study was conducted on data of 23 patients with pancreatic duct diseases who were underwent peroral pancreatoscopy (POPS) at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from August 2020 to October 2022. The intraoperative observation, postoperative complications, and the diagnosis and treatment of POPS for pancreatic duct diseases were analyzed. All patients underwent POPS and achieved technical success. Among them, 7 patients were diagnosed as having intraductal papillary mucinous neoplasm of pancreas and 3 pancreatic malignant tumor. Eight patients with pancreatolithiasis accepted laser or eletrohydraulic lithotripsy under POPS. Abdominal pain improved in 2 patients with chronic pancreatitis after treatment. Melena disappeared in 2 patients with pancreatic duct hemorrhage or pancreatic enterostomy inflammation after conservative treatment. The symptom of 1 patient with pancreatic enterostomy stenosis improved after balloon dilation. There was no complication in the 23 patients, and the operation time was 35-90 min. The results indicate POPS is safe, effective with distinctive advantages in the diagnosis and treatment for pancreatic duct diseases.

Objective : To investigate the efficacy of standardized allergen subcutaneous immunotherapy (SCIT) in children with asthma sensitized to single dust mite allergens versus multiple allergens and to assess the safety of SCIT. Methods : 62 children with confirmed allergic asthma who received standardized allergen SCIT were retro⁃ spectively analyzed and divided into the monosensitized group (dust mite results≥ + + + ) and the polysensitized group (dust mite results ≥ + + + combined with other positive allergens) according to the results of skin pricktest , we observed the changes of pulmonary function , medication score and visual analog scale (VAS) scores , children asthma control test (C - ACT) scores , asthma control questionnaire (ACQ) scores before and after treatment in both groupsand compared the efficacy of the two groups. The incidence of local and systemic adverse effects was recorded during treatment in all children to assess the safety of SCIT. Results : Standardized allergen SCIT treatmentimproved lung function parameters , medication scores and VAS scores , C ⁃ACT scores , ACQ scores in both the monosensitized and polysensitized groups , with statistically significant differences before and after treatment (P < 0. 05) . In comparison between the two groups , lung function parameters [forced expiratory flow at 50% vital capacity(FEF50% ) , maximum midexpiratory flow(MMEF)] , medication scores , C ⁃ACT scores and ACQ scores improved significantly in the monosensitized group compared with the polysensitized group after treatment ( P <0. 001) . 62 patients received a total of 2 606 injections during the treatment of SCIT , 6 children had a total of 10 local adverse reactions and 3 children had 3 mild to moderate systemic adverse reactions , with an incidence of 0. 38% for local adverse reactions and 0. 12% for systemic adverse reactions. Conclusion The children with asthma in both the monosensitized group and polysensitized group achieved significant and safe clinical outcomes under standardized allergen SCIT. The children in the monosensitized group had more obvious clinical effects than the polysensitized group under standardized allergen SCIT.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Objective:To assess the effectiveness of influenza vaccine in children aged 6-72 months.Methods:The cohort study was conducted based on community child vaccination clinics in Yiwu and Yongkang counties of Zhejiang province. From October 2017 to December 2017, a total of 1 752 children aged 6-72 months were enrolled from 10 child vaccination clinics. The questionnaire survey was conducted after the written consents were obtained from the parents or legal guardians of the children. Then, a follow up was conducted for enrolle children until 30 April 2018, the influenza vaccination status and the number of influenza-like illness (ILI) cases, hospital visit due to ILI, self-medication due to ILI were observed and recorded every month. Vaccine effectiveness (VE) was estimated by using the generalized linear model (GLM) where dependent variables were the number of ILI cases, hospital visit and self-medication respectively.Results:Of the 1 752 children, 925 (52.80%) were boys and the median age was 30.00 months. The cumulative observation was 308 166 person days at the end of 2017-2018 season, with 5.27 ILI cases per 1 000 person days, 3.41 hospital visit due to ILI per 1 000 person days, 1.45 self-medication due to ILI per 1 000 person days. Of the 1 752 children, 643 received the influenza vaccination in 2017-2018 season. Compared with unvaccinated children, the VE was 23.5% against ILI case number (95% CI: 15.1%-31.1%), 19.3% against hospital visit due to ILI (95% CI: 8.2%-29.1%) and 25.8% against self-medication due to ILI (95% CI: 9.3%- 39.3%). Modeling splitting 643 children with 2017-2018 vaccination into those before and after vaccination, the influenza VE was 31.9% against ILI case number (95% CI: 12.7%-46.9%), 32.6% against hospital visit due to ILI (95% CI: 8.6%-50.3%) and 44.3% against self-medication due to ILI (95% CI: 11.9%-64.8%) in children aged 36-72 months. However, the children aged 6-35 months showed no significant VEs. For the VE analysis in children with different vaccination status, the VEs were significant if they received vaccination in both 2016-2017 season and 2017-2018 season or only in 2017-2018 seasons. The VE was not demonstrated among the children who were immunized only in 2016-2017 season. Conclusion:Influenza vaccination is moderate effective in preventing the incidence of ILI and hospital visit and self-medication in children in influenza season, the protection effect in children aged 36-72 months is better than that in children aged 6-35 months.

Objective: To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods: The test-negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza-like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test-positive were selected as the case group (403 cases). Test-negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non-randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results: The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co-infection of influenza [A(H₃N₂)+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI:-80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H₃N₂) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI:18%-88%) against all type influenza. Conclusion Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.

Objective To evaluate the effect of hypothermia on the endotracheal tube cuff pressure during cardiopulmonary bypass in the pediatric patients with congenital heart disease. Methods Forty pedi-atric patients of both sexes, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, aged 1 months-14 yr, weighing 3-58 kg, scheduled for elective surgery for congenital heart disease using cardiop-ulmonary bypass, were included in this study. All the pediatric patients were intubated with a cuffed endo-tracheal tube. After anesthesia induction and endotracheal intubation, the air was injected into the cuff to make the cuff pressure reach 20 cm H2 O ( baseline) . The endotracheal tube cuff pressure was recorded when the esophageal temperature was reduced to 34, 32, 30, 28 and below 28℃ and returned to 28, 30, 32, 34 and 36 ℃. Results The cuff pressure was significantly decreased when the esophageal temperature was reduced to 30 and 28 ℃ and below 28 ℃ and returned to 28, 30, 32 and 34 ℃ as compared with the baseline ( P<0. 05) . Conclusion Hypothermia can reduce the endotracheal tube cuff pressure during car-diopulmonary bypass, and it is recommended to routinely monitor the cuff pressure in the pediatric patients with congenital heart disease.