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 the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To evaluate the application of enhanced recovery after surgery in patients undergoing laparoscopic gastric cancer surgery and its impact on the systemic inflammatory response (SIR).Methods:The clinical data of patients undergoing laparoscopic gastric cancer surgery at the Department of Gastrointestinal Surgery, Zhongnan Hospital, Wuhan University from Mar 2021 to Mar 2023 was retrospectively analyzed.Results:A total of 234 patients with gastric cancer were enrolled (120 cases in ERAS group and 114 cases in routine group). There were no significant differences in preoperative indexes between the two groups (all P>0.05). After laparoscopic surgery, the postoperative ventilation time and hospital stay of patients in ERAS group were significantly shorter than those in the conventional group (all P<0.05). Neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index of patients in ERAS group were significantly lower on day 1 and day 3 after surgery than in conventional group (all P<0.05). The ratio of lymphocyte to monocyte (LMR) in ERAS group was significantly higher than that in conventional group on day 1 and day 7 after surgery (all P<0.05). Conclusions:ERAS can improve postoperative SIR indexes in patients undergoing laparoscopic gastric cancer surgery, shorten postoperative recovery time, and enhance the efficacy of laparoscopic gastric cancer surgery by reducing perioperative systemic inflammation.

Cohort study of children and adolescents health is an ideal method to explore health-related problems from childhood to adulthood, to which more attention has been paid. This paper summarizes the progress in cohort study of children and adolescents health conducted both at home and abroad by introducing the study design, main contents. Emphasizing the international exchange and cohort integration, continuously expanding cohort research field, and using multi-source data for high-quality follow-up have become the trend of cohort study of children and adolescents health.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell