Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

This paper reviewed the research progress in the differentiation and treatment of precancerous lesions of gastric cancer(PLGC)with traditional Chinese medicine(TCM)in the recent 10 years.PLGC refers to the intestinal metaplasia and dysplasia of gastric mucosa developed from chronic atrophic gastritis.As an intermediate stage between chronic atrophic gastritis and gastric cancer,PLGC progresses slowly.TCM has certain advantages in the treatment of PLGC.PLGC can be mainly differentiated as five TCM syndrome types:spleen-stomach weakness syndrome,damp-heat in the spleen and stomach syndrome,qi stagnation in the liver and stomach syndrome,stasis obstruction in the stomach collateral syndrome,and stomach-yin deficiency syndrome.The popularization of gastroscopy technology has promoted the development of microscopic syndrome differentiation of gastric diseases.The combination of microscopic syndrome differentiation and macroscopic syndrome differentiation provides more theoretical supports for the TCM syndrome differentiation and treatment of PLGC.The basic pathogenesis of PLGC is due to the weakness of spleen and stomach and the disordered qi movement in the spleen and stomach,complicated by the accumulation of pathological factors such as damp-heat,stasis-toxin,phlegm-damp,and then the stomach-yin will be consumed over time.An amount of clinical studies on the treatment of PLGC with Chinese medicine have been carried out in recent years.The Chinese medicine treatment of PLGC is mainly through benefiting qi and invigorating spleen,assisted by the methods of soothing liver and activating blood,resolving dampness and eliminating stasis,resolving stasis and removing toxins,and nourishing yin and benefiting stomach,so as to prevent the PLGC progressing to gastric cancer.There are few studies on acupuncture treatment of precancerous lesions of gastric cancer.Therefore,it is necessary to carry out more strict and standardized multi-center large-sample RCTs,and to further study the therapeutic mechanism of acupuncture and moxibustion for PLGC,in order to provide more high-level evidence for the treatment of PLGC with TCM therapy.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

Objective To study the effects of different SBRT-VMAT plans for non-small cell lung cancer(NSCLC)with unilateral ipsilateral double metastatic lesions on received dose,monitor unit(MU),conformity index(CI)and gradient index(GI)of the lung,so as to provide references for therapy planning of the patient above.Methods A total of 11 NSCLC patients with unilateral ipsilateral double metastatic lesions were selected,with three plans developed for each patient by the volumetric modulated arc therapy(VMAT).The inner target areas ITV1 and ITV2 were contoured based on the maximum projection image of the 4D-CT localization mode,which were uniformly expanded externally by 3 mm to obtain the plan target area PTV1 and PTV2,and then PTV1 was added with PTV2 to get PTV12.The first planning mode had the centers of PTV1 and PTV2 target areas as the treatment centers,and two separate plans of plan-1 and plan-2 were developed and then combined into a plan-sum plan for dose evaluation;the second planning mode had the centers of PTV1 and PTV2 target areas as the treatment center,resepctively,and a multicenter plan(plan-D)was formed.The third planning mode had the center of PTV12 target area as the treatment center,and a single-center plan(plan-S)was designed.To meet the requirements of prescribed dose,plan-1 and plan-2 of plan-sum were normalized to PTV1 and PTV2 95％volume and plan-S and plan-D were normalized to PTV 12 95％volume.The three planning modes were compared in terms of received dose,MU,CI and GI of the lung.SPSS 25.0 software was carried out for statistical analysis.Results Plan-S had no significant differences with Plan-sum except V5(P＞0.05),whose V10,V20,V30 and mean dose were significantly lower than those of plan-sum(P＜0.05);plan-D had its received dose and mean dose statistically lower than those of plan-sum(P＜0.05);plan-S and plan-D had no obvious differences in received dose of the lung(P＞0.05).Plan-sum had the CI significantly lower than those of plan-S and plan-D(P＜0.05);plan-S and plan-D had no statistically differences in CI(P＞0.05).Plan-D had the GI significantly lower than plan-S and plan-sum(P＜0.05).Plan-S and plan-sum had no significant differences in GI(P＞0.05).Plan-D and plan-sum had no statistical differences in MU(P＞0.05),which had the MUs significantly higher than that of plan-S(P＜0.05).Conclusion A multicenter planning mode may be used for optimizing dose distribution and enhancing conformity in case the patient can tolerate prolonged immobilization in a fixed position,and a singlecenter planning mode should be adopted to shorten treatment time when the patient is in poor physical conditions.[Chinese Medical Equipment Journal,2024,45(10):49-53]

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.
Child ; Humans ; Cholesterol, HDL ; Cross-Sectional Studies ; Non-alcoholic Fatty Liver Disease/complications* ; Overweight/complications* ; Pediatric Obesity/epidemiology* ; Prevalence ; Adolescent

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors