OBJECTIVE: To reveal the gap between the evidence of systematic reviews (SRs) and clinical concerns by systematically summarizing the evidence on acupuncture and moxibustion for frozen shoulder and investigating the concerns and needs of clinicians in treatment with acupuncture and moxibustion for this disease. METHODS: The articles of SR and Meta-analysis on acupuncture and moxibustion for frozen shoulder were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library, starting from the inception of each database up to December 31st, 2022. Two researchers screened the articles and extracted data independently. Using AMSTAR-2, the methodological quality of the included studies was evaluated. Based on systematic reviews and expert discussion, a questionnaire on clinical concerns of acupuncture and moxibustion for frozen shoulder was developed and distributed to clinicians. The discrepancies between the evidence and clinical concerns were compared from 5 dimensions, including population, interventions, control measures, outcome indicators and review time points. RESULTS: The evidence gaps existed between SRs and clinical concerns. In the existing studies, the needs of personalized treatment were not fully considered in terms of different syndromes/patterns of frozen shoulder and stages of illness, the outcome indicators were not employed properly, the time for outcome measurement was vague, the control groups were set up outside of standardization, and the methodological quality was lower. CONCLUSION It is suggested that future studies should improve the quality of methodology, lay more consideration to different patient groups, optimize outcome indicators and standardize the setting of control groups, so as to better meet the needs of patients and achieve the best match between evidence and clinicians' needs.
Humans ; Acupuncture Therapy ; Bursitis/therapy* ; Evidence Gaps ; Moxibustion ; Systematic Reviews as Topic ; Meta-Analysis as Topic

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

PURPOSE: To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI. METHODS: In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05. RESULTS: The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001). CONCLUSION 4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals ; Synovitis/etiology* ; Mice ; Osteoarthritis/etiology* ; Disease Models, Animal ; Male ; Succinates/pharmacology* ; Mice, Inbred C57BL ; X-Ray Microtomography

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates

The research progress in key technologies for dynamic perception of battlefield casualties was reviewed,including unmanned equipment dynamic mapping,dynamic environment semantic segmentation and casualty detection and identification.The discussion also covered the current state of research on casualty dynamic perception equipment in aerial and ground domains.The development trends of key technologies and equipment for dynamic perception of battlefield casualties were pointed out,and references were provided for enhancing the efficacy of battlefield casualty care and improving medical service support capabilities.[Chinese Medical Equipment Journal,2024,45(9):95-108]

Objective To investigate the mechanism of action of biochanin A(BCA)on osteoarthritis through in vitro experiments.Methods Primary rat chondrocytes were extracted and cultured,and then divided into the control group(without inducer or interferant),the model group[10 ng/mL interleukin-1 β(IL-1 β)induction],and the BCA group(10 ng/mL IL-1β induction+0,3,6,12,24,48 μmol/L BCA intervention).Cell activity was detected by methyl thiazolyl tetrazolium(MTT)method.Senescence-associated β-galactosidase(SA-β-gal)staining was used to observe cell senescence.Intracellular inflammatory factors and oxidative stress indexes were detected by enzyme-linked immunosorbent assay(ELISA),the levels of related proteins were detected by Western blot,and the affinity between BCA and Nrf2 was verified by molecular docking technology.Results After screening the concentration of BCA with MTT,6,12 and 24 μmol/L BCA were selected for subsequent experiments.Compared with the control group,the chondrocyte activity and the activities of catalase(CAT)and superoxide dismutase(SOD)in the model group were significantly decreased(P＜0.05).The number of SA-β-gal positive cells and expres-sion levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and malondialdehyde(MDA)increased significantly(P＜0.05).The expression levels of type Ⅱ collagen(COL2A1)and aggrecan(ACAN)were significantly decreased(P＜0.05).Compared with the model group,the above conditions were significantly reversed in the BCA group(P＜0.05).In addition,BCA could significantly reduce the degrada-tion of inhibitor kappa B alpha(IκB-α)and nuclear translocation of NF-KBp65,and promote the expression of Nrf2 in the nucleus and the expression of human heme oxygenase-1(HO-1)in whole cells(P＜0.05).The results of molecular docking further confirmed that BCA had the highest affinity with Nrf2.Conclusion BCA can inhibit oxidative stress and inflammation of osteoarthritis chondrocytes by regulating Nrf2/NF-KB signaling pathway in vitro,and alleviate joint injury.