Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

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 was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

This study was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

Objective:To study the effects of dapagliflozin on left ventricular diastolic function in elderly patients with heart failure with preserved ejection fraction(HFpEF)during acute decompensation.Methods:A total of 160 elderly patients with HFpEF during acute decompensation treated in Department of Geriatrics,Fujian Provincial Geriatric Hospital were retrospectively enrolled between January 2021 and January 2024.According to different therapeutic regimens,they were divided into routine treatment group(n=80,routine anti-heart failure drug thera-py)and combined dapagliflozin treatment group(n=80,dapagliflozin on basis of routine anti-heart failure drug therapy).All patients were treated for 3 months.The clinical curative effect,changes of left ventricular diastolic function indexes[early diastolic mitral annular peak velocity(e'),ratio of left ventricular early diastolic filling peak velocity(E)to e'(E/e'),tricuspid regurgitation velocity(TRV),left atrial diameter(LAD)],inflammatory factors[serum amyloid A(SAA),high sensitive C-reactive protein(hsCRP),interleukin-6(IL-6)],myocardial enzymes[lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB),α-hydroxybutyrate dehy-drogenase(α-HBDH)]and N-terminal pro brain natriuretic peptide(NT-proBNP),and the occurrence of adverse re-actions were compared between the two groups.Results:Compared with routine treatment group,total effective rate was significantly higher in combined dapagliflozin treatment group(85.00％vs.95.00％,P=0.035).After treatment,E/e',TRV,LAD,levels of SAA,hsCRP,IL-6,LDH,CK,CK-MB,α-HBDH and NT-proBNP in combined dapaglifloz-in treatment group were significantly lower than those in routine treatment group(P＜0.01 all).There was no significant difference in the incidence rate of adverse reactions between the two groups(P=0.718).Conclusion:Dapagliflozin can significantly improve left ventricular diastolic function and effectively alleviate the progression of heart failure in elderly pa-tients with HFpEF during acute decompensation,which has certain clinical significance.

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 investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint.Methods Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021.They were divided into group A and group B according to different surgical methods.There were 42 patients in group A,including 26 males and 16 females,aged from 44 to 72 years old with an average of(60.57±4.62)years,who underwent revision with metal cushion block and Jumbo cup.There were 41 patients in group B,including 22 males and 19 females,aged from 42 to 71 years old with an average of(58.74±4.25)years,who under-went revision with metal cushion block and bone cement mortar cup.The operation related indexes,Harris hip function score and visual analogue scale(VAS)of pain before operation,1 month and 12 month after operation were compared between two groups.The results of X-ray imaging examination(hip rotation center height,acetabular abduction angle,femoral eccentricity and imaging standard qualification rate)before and 12 month after operation were evaluated,and the incidence of complica-tions was compared between two groups.Results There was no significant difference in operation time,intraoperative bleeding volume and postoperative drainage volume between two groups(P＞0.05).Both groups were followed up for 12 to 36 months with an average of(25.36±3.59)months.The scores of pain,function,deformity and Harris'total score in the two groups at 1 month after operation were higher than those before operation(P＜0.05),and the scores of pain,function,deformity,joint activ-ity and Harris'total score in two groups at 1 year after operation were higher than those before operation and 1 month after op-eration(P＜0.05),and the above scores in group A were higher than those in group B at 1 year after operation(P＜0.05).The VAS of two groups decreased successively at 1 month and 1 year after operation(P＜0.05),but there was no significant differ-ence in both groups at each time point(P＞0.05).The femoral eccentricity increased in both groups at 1 year after operation(P＜0.05),and group A was higher than group B(P＜0.05).The height of rotation center and acetabular abduction angle de-creased in both groups at 1 year after operation(P＜0.05),and the height of rotation center in group A was lower than that in group B(P＜0.05),but there was no significant difference in acetabular abduction angle between two groups(P＞0.05).The imaging qualification rate of group A was higher than that of group B(P＜0.05).There was no significant difference in the inci-dence of adverse reactions between two groups(P＞0.05).Conclusion Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function,and restore the hip joint rotation center,femoral eccen-tricity and acetabular abduction angle,with obvious clinical effect.