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

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

This article reports a rare case of proliferative glomerulonephritis with monoclonal immunoglobulin deposits. The patient, a middle-aged woman, exhibited clinical manifestations including nephrotic syndrome, microscopic hematuria, renal insufficiency, hyperglycemia, and bilateral diabetic retinopathy. Notably, monoclonal bands were absent in both blood and urine immunofixation electrophoresis. Renal biopsy revealed membranoproliferative glomerulonephritis, with immunofluorescence revealing exclusive petal-like deposition of IgG3 subtype along the capillary loop. Electron microscopy demonstrated segmental thickening of the glomerular basement membrane, along with electron dense deposits in the subendothelial and mesangial areas, lacking discernible substructure. The diagnosis comprised proliferative glomerulonephritis with monoclonal immunoglobulin deposition concurrent with diabetic nephropathy. Subsequent sequential treatment with daratumumab and cyclophosphamide over 6 months led to partial remission of nephrotic syndrome, normalization of renal function, and significant improvement of anemia. During the 24-month follow-up period, no serious adverse reactions occurred.

Objective:To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).Methods:A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).Results:WES revealed that the proband has harbored a heterozygous c. 1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband′s father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3). Conclusion:The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.

OBJECTIVE： To establish a method for simultaneous determination of 27 kinds of heavy metals and trace elements in Halloysitum album from different origins. METHODS： The sample was dissolved by wet digestion. Using inductively coupled plasma mass spectrometry （ICP-MS）， carrier gas was argon and collision gas was helium； plasma gas flow rate was 15.0 L/min；   flow rate of carrier gas was 1.17 L/min and collision gas flow rate was 5.0 mL/min； atomizer was Barbinton， and sampling depth was 8.0 mm； atomizing chamber temperature was 2 ℃； radio frequency power was 1.3 kW； peristaltic pump revolutions was 30 r/min. In full quantitative analysis model， the number of test points was 3， the analysis time was 0.1 s， the repetition was 3 times， clustering analysis was conducted by using PASW Statistics 18.0 software. RESULTS： The linear range of 27 kinds of heavy metals and trace elements were 0-200 μg/L（r≥0.996 5）； the quantitative limit was 0.003 41-75.485 μg/L and the detection limit was      0.001 1-24.350 0 μg/L. RSDs of precision， stability and repeatability tests were all less than 7％； average recovery was 72.3％- 129.1％ （RSD was 0.9％-9.4％， n＝6）. The content of Al was 0.01-123 220.20 mg/kg， and Al was the element with the highest content. Li， Na， Mg， K， Ca， V， Mn， Fe， Co， Ni， Zn， Ga， Se， Rb， Sr， Ba and U were the principal components of trace elements and could be used as characteristic elements； 26 batches of Halloysitum Album samples could be grouped into 4 categories. CONCLUSIONS： The established method is simple， fast and highly sensitive， can improve the precision and accuracy of test results， and it is suitable for the determination of heavy metals and trace elements in Halloysitum album.

OBJECTIVE: To explore the application value of rectal prolapse constipation balloon in single auxiliary defecation. METHODS: Forty-one patients with moderate or severe rectocele were treated with a rectocele constipation balloon through the vagina. The defecography and VAS scores were compared before and after implantation. RESULTS: There was a significant difference between the anorectal angle, rectocele, and VAS scores before and after intervention in defecography (<0.01). CONCLUSIONS A single assisted defecation of the rectocelicular constipation balloon is feasible.
Constipation ; diagnosis ; Defecation ; Defecography ; instrumentation ; Female ; Humans ; Rectal Prolapse ; Rectocele

Objective To discuss whether it is necessary to integrate metabolic indices into diagnosis of polycystic ovary syndrome (PCOS).Methods Taking ESHRE/ASRM diagnosis as the gold standard,51 women with PCOS and 47 women without PCOS were selected and divided into the intervention group and control group respectively from the Department of Gynecology in the Second Affiliated Hospital of Kunming Medical University between January 2013 and July 2014.Logistic regression based on principal component analysis and significant variables chosen through single factor analysis were used to establish the new diagnostic model which combined reproductive indices and metabolic indices.We evaluated the validity and reliability of the new diagnostic model by using ROC curve analysis.Finally,we analyzed the consistence and difference between the new diagnostic model and the gold standard.Results Thirteen significant variables were chosen using single factor analysis.ROC analysis showed that an area under the curve was 0.976 (P＜0.001) and the optimal cut-off point was 0.526 with a sensitivity of 96.08％,a specificity of 93.62％ and a consistency of93.88％.The new diagnostic model had superior validity and reliability.The two diagnostic methods had strong consistence (Kappa=0.877,P＜0.001) and no difference (x2=0.167,P=0.688).Conclusion Considering that the integration of metabolic indices does not change the diagnosis result,we come to a conclusion that it is unnecessary to integrate metabolic indices into diagnosis of PCOS.

Objective To investigate the antimicrobial susceptibility of spectinomycin?minocycline?azithromycin and sparfloxacin to mycoplasma(Uu and Mh)and therapeutic effect of spectinomycin to my-coplasma infection in genitourinary tract.Methods①The susceptibility test:each of the4drugs was divided into two concentrations.One was at1?g/mL(sensitive concentration)and the other was at4?g/mL(resistant concentration).If mycoplasma does not grow in both concentrations,it means the drug tested is sensitive.If it grows in both concentrations,the drug tested is resistant.If mycoplasma grows in lower concentration and does not in higher concentration,it means moderate sensitive.②Treatment regimen:Spectinomycin was injected,2g/d IM,for7-10days as a course of treatmeant.Patients were followed-up7days later and2~4weeks after treatment.Results①Among1658specimens,519were found Uu positive,and61Mh positive.The resis-tance rates of Uu to4different drugs were:7.7%for minocycline,21.4%for sparfloxacin,13.9%for azithromycin and7.3%for spectinomycin.Whereas,those of Mh were:18.0%,45.9%,54.1%,and29.5%re-spectively.②The clinical effect of spectinomycin was:out of43treated patients,37(86.0%)cured,4(9.3%)markedly improved,2(4.7%)failed.Total effective rate was95.3%and so was the elimination rate of my-coplasma.Conclusion The resistant rate of mycoplasma to spectinomycin is lower than that to minocycline?azithromycin and sparfloxacin,and the former is widely used in the treatment of mycoplasma(especially Uu)infection,with a satisfactory clinical effect.