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

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

To improve the quality evaluation system of Hibisci Mutabilis Folium, this study established high performance liquid chromatography(HPLC) fingerprints of Hibisci Mutabilis Folium and evaluated the quality differences of medicinal materials from different places of production by chemometrics. Furthermore, a content measurement method of differential components was established based on quantitative analysis of multi-components by single-marker(QAMS). The fingerprints of 17 batches of Hibisci Mutabilis Folium from different places of production were constructed, with a total of 19 common peaks marked and seven components confirmed. The similarity between the sample fingerprints and the reference fingerprints ranged from 0.890 to 0.974. By utilizing principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA), the chemical patterns of fingerprints were identified. Five components that could be used to evaluate the quality differences of Hibisci Mutabilis Folium were screened, namely peak 6(quercetin 3-O-β-robinobioside), peak 7(rutin), peak 9(kaempferol-3-O-β-robinobioside), peak 10(kaempferol-3-O-rutinoside), and peak 14(tiliroside). The relative correction factors of isoquercitrin, kaempferol-3-O-β-robinobioside, kaempferol-3-O-rutinoside, kaempferol-3-O-β-D-glucoside, and tiliroside were measured with rutin as the internal reference. The QAMS method was established for the content measurement of six flavonoids, and the results showed there was no significant difference compared to the results obtained by an external standard method. In summary, the HPLC fingerprints and QAMS method established in the study, demonstrating stability and accuracy, can provide a reference for the overall quality evaluation of Hibisci Mutabilis Folium.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Principal Component Analysis

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.

Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Objective To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P＞0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P＜0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P＜0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.

Objective To systematically evaluate the clinical efficacy and safety of therapy of tonifying kidney and promoting blood circulation(shortened as Bushen Huoxue method)combined with cyclosporine plus androgen for the treatment of aplastic anemia(AA).Methods Randomized controlled trials(RCTs)of Bushen Huoxue method combined with cyclosporine plus androgen(trial group)versus cyclosporine plus androgen alone(control group)for the treatment of AA were retrieved from the major domestic and oversea databases,and then high-quality RCTs that met the inclusion criteria were screened.RevMan 5.3 software was used for meta-analysis.Results A total of 6 RCTs involving 365 patients were included.The results of meta-analysis showed that the total effective rate of AA in the trial group was significantly superior to that of the control group[OR=4.43,95%CI(2.50,7.84);P＜0.000 01].The trial group was superior to the control group on improving the peripheral blood indicators such as hemoglobin(HGB)level[MD=14.85,95%CI(10.66,19.05);P＜0.000 01],white blood cell(WBC)level[MD=0.61,95%CI(0.21,1.01);P=0.003],platelet(PLT)level[MD=16.51,95%CI(9.28,23.75);P＜0.000 01],and did not increase the incidence of adverse reactions such as hirsutism[OR=0.24,95%CI(0.10,0.61);P=0.003],acne[OR=0.30,95%CI(0.13,0.66);P=0.003],and abnormal liver function[OR=0.28,95%CI(0.09,0.83);P=0.02].Conclusion Bushen Huoxue method combined with cyclosporine plus androgen for the treatment of AA is superior to the use of cyclosporine plus androgen alone on enhancing clinical efficacy and improving the peripheral blood indicators,and has certain advantages in reducing the incidence of adverse reactions.