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 investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT).Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills.GeneCards,PharmGKB,and TTD databases were used to screen PCOS and EMT disease targets,respectively.The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI)network diagram was drawn in the STRING platform,and Cytoscape was used to optimize the PPI network and screen the core targets.R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and AutoDockTools was for molecular docking.Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT.The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin,baicalein,and the core targets were AKT1,EGFR,IL-6,TNF,and TP53.GO functional analysis yielded 2 020 biological process,34 cellular components,126 molecular functions,and KEGG enrichment analysis yielded 165 signaling pathways.Molecular docking showed that the core components in the formula docked well with the targets.Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,and chemical carcinogenesis-receptor activation through quercetin,β-sitosterol,kaempferol,hederagenin,and baicalein,and act on AKT1,EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

Electrocardiography ; GTP-Binding Protein beta Subunits/genetics* ; Humans ; Mutation ; Pedigree ; Sick Sinus Syndrome/genetics*

Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.
Autopsy ; Forensic Pathology/trends* ; Forensic Toxicology ; Humans ; Metabolomics ; Postmortem Changes

OBJECTIVE: To investigate whether cell preservation solution can prolong the survival time of leukemia cells and increase the survival rate, so as to improve the detection rate of central nervous system leukemia. METHODS: Kasumi cells were added into cerebrospinal fluid (CSF) supernatant with or without cell preservation solution to compare cell viability and biological characteristics at different time point. Wright Giemsa staining was used to compare cell morphology; cell counting, CCK-8 method, and trypan blue staining were used to compare the cell number, and flow cytometry was used to compare the cell viability. The expression of AML-ETO tumor fusion gene was detected by fluorescence quantitative RT-PCR. RESULTS: At different time points (8 h and 24 h), the survival, molecular biological characteristics and RT-PCR result of the cells in CSF with cell preservation solution were significantly better than those in normal cerebrospinal fluid. CONCLUSION Cell preservation solution can effectively improve the survival time and survival rate of leukemic cells, thereby increase the detection rate of CNS leukemia.
Central Nervous System Neoplasms ; Core Binding Factor Alpha 2 Subunit ; Humans ; Leukemia ; RUNX1 Translocation Partner 1 Protein

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers ; Cohort Studies* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Lymph Nodes ; Nasopharynx ; Plasma ; Prognosis ; Radiotherapy* ; Tumor Burden*

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

OBJECTIVETo study the clinical effect and surgical operating points of pararectus approach for the internal fixation of acetabular both-column fractures with concurrent displaced quadrilateral plate fractures.

METHODSFrom January 2012 to December 2013, in the Third Affiliated Hospital of Southern Medical University, 15 patients with acetabular both-column fractures and displaced quadrilateral plate fractures were surgically managed through the pararectus approach. There were 11 male and 4 female patients, with an average age of 40 years (from 19 to 61 years). According to Judet-Letournel classification, there were 9 anterior column plus posterior hemitransverse fractures, 6 both-column fractures, 8 cases involving the pelvic fracture. All these fractures were treated through the pararectus approach, in the horizontal position with general anesthesia. The pre-bended plate was placed in interior pelvic ring to fix the anterior wall, anterior column and quadrilateral plate in direct sight. Then, the posterior column was exposed and fixed with antegrade lag screw. Patients were followed up in 4 weeks, 12 weeks, 6 months, 1 year after the operation, and the anteroposterior radiograph of pelvis and the X-ray examination of the fractured hip was performed.

RESULTSAll the 15 cases underwent the operation successfully. Postoperative X-ray and CT exams showed excellent and good reduction of anterior column, posterior column and quadrilateral plate, with none surgical complication occurred. According to the Matta radiological evaluation postoperatively, reduction of acetabular fracture was rated as excellent in 9 cases, good in 3 cases and poor in 3 cases. The rate of excellent and good was 12/15. After 8 to 18 months' follow-up (median follow-up time was 14 months), all the patients gained bone union. According to the modified Merle D'Aubigne and Postel scoring system, 9 cases were excellent, 4 were good, and 2 were fair. The rate of excellent and good was 13/15.

CONCLUSIONSSurgical management of acetabular fractures through the pararectus approach can provide adequate exposure of reducing and fixing both-column acetabular fractures with concurrent displaced quadrilateral plate fractures, which has a good effect in clinical application.

Acetabulum ; pathology ; surgery ; Adult ; Anesthesia, General ; Bone Plates ; Bone Screws ; Female ; Fracture Fixation, Internal ; methods ; Hip Fractures ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Pelvic Bones ; pathology ; surgery ; Postoperative Period ; Spinal Fractures ; Treatment Outcome ; Young Adult