Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90％confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00％and 125.00％,and the 95％upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00％and 125.00％.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.

Objective:Due to the limitation of traditional identification methods of Chinese medicinal materials， the study established a rapid method to identify Persicae Semen mixed with Armeniacae Semen Amarum by allele-specific polymerase chain reaction （PCR）. Method:By comparing the ribosomal DNA internal transcribed spacer （ITS） gene sequences of Persicae Semen and Armeniacae Semen Amarum， single nucleotide polymorphism （SNP） sites were searched and specific primers were designed. Different Persicae Semen and Armeniacae Semen Amarum samples were amplified by PCR， the effects of annealing temperature， primer concentration and cycle number on the PCR reaction system were optimized， and the specificity and detection limit of this method were investigated. In addition， the established PCR method was used to detect the samples of Persicae Semen mixed with different proportion of Armeniacae Semen Amarum from different sources and producing areas. Result:A specific PCR method for identifying Persicae Semen mixed with Armeniacae Semen Amarum was established. When the annealing temperature was 63 ℃ and the number of primer cycles was 30， only Armeniacae Semen Amarum could be amplified with 432 bp specific band， while Persicae Semen samples did not have this band. The minimum detection limit of this method for Armeniacae Semen Amarum was 0.2 ng， and the detection limit for Armeniacae Semen Amarum adulterated in Persicae Semen was 1%. Conclusion:The established allele-specific PCR method can accurately detect whether there is Armeniacae Semen Amarum in Persicae Semen， which can provide experimental basis for the quality control of Persicae Semen and guarantee the safety of its clinical use.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

BACKGROUND: Until now, there are no reliable methods for the treatment of urinary incontinence after radical prostatectomy. Some limitations exist in drug therapy, mid-urethral suspension, and filling agent treatment. Therefore, the use of autologous adipose-derived stem cells (ADSCs) is expected to become a first-line treatment strategy for urinary incontinence after radical prostatectomy. OBJECTIVE: To report our initial experience with transurethral injection of autologous ADSCs for the treatment of urinary incontinence after radical prostatectomy. METHODS: Patients and their families were informed of possible risks and benefits prior to the participation in the trial. After providing written informed consent, six patients with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from each patient by liposuction. ADSCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADSCs and adipose tissue was transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed through a 24-hour pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) through 12-week follow-up. RESULTS AND CONCLUSION: Urine leakage volume was improved with time in all patients in the 24-hour pad test, with the exemption of temporal deterioration in two patients at the first 2 weeks post-injection. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 4.312 kPa to 6.223 kPa at 12 weeks after cell injection. MRI results showed an increase in functional profile length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were undetected in any case during the follow-up. To conclude, the transurethral injection of autologous ADSCs can be a safe and effective treatment for urinary incontinence after radical prostatectomy.

Objective To investigate the clinical effect of tiotropium combined with seretide in the treatment of patients with bronchial asthma.Methods Ninety cases of bronchial asthma were randomly divided into treatment group and control group,each group 45 cases.Control group was given seretide accuhaler.On the basis of control group,treatment group was given tiotropium inhalation powder spray treatment,18 μg each time,1 times a day.All patients were treated for 12 weeks.The pulmonary function changes,eosinophil cationic protein (ECP),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),the clinical effect and treatment satisfaction were compared between the two groups.Results After treatment,total effective rates in control group and treatment group were 82.22％ (37 cases/45 cases),97.78％ (44 cases/45 cases),with significant difference (P ＜ 0.05).After treatment,the levels of forced expiratory volume in one second (FEV1) in treatment and control groups were (1.46 ± 0.32),(1.08 ± 0.25) L,the levels of peak expiratory flow (PEF) were (4.35± 1.12),(3.77 ± 1.02) L · s-1,the levels of forced vital capacity (FVC) were(2.18 ±0.36)％,(1.71 ± 0.31) ％,all with significant difference (all P ＜ 0.05).After treatment,the levels of ECP in treatment and control groups were (160.60 ± 20.30),(289.70 ± 25.60) ng · mL-1,the levels of IL-6 were (28.90 ± 5.70),(53.70 ± 8.80) pg · mL-1,the levels of TNF-α were (10.40 ± 2.30),(17.60 ± 3.10) ng · mL-1,all with significant difference (all P ＜ 0.05).The adverse drug reactions in treatment group were palpitations,hoarseness,with the incidence of 11.11％ (5 cases/45 cases).The adverse drug reactions in control group were hoarseness,with the incidence of 8.89％ (4 cases/45 cases),with no significance difference (P ＞ 0.05).Conclusion The clinical effect of tiotropium combined with seretide in the treatment of patients with bronchial asthma is great,and can increase patients' treatment satisfaction.

OBJECTIVETo investigate the effects of Shadu Cao Mixture (SDCM, traditional Chinese medicine) on immune functions of immunosuppression mice.

METHODSFifty BALB/C mice were randomly divided into blank control group, model group, SDCM low-dose, middle-dose and high-dose group. Except the blank control group, other groups were intraperitoneal injected with cyclophosphamide (40 mg/kg) to establish immunosuppression mice model. The blank control group and model group received gavage administration with nonnal saline, while the other groups received gavage administration with different doses of SDCM (10, 20, 40 m/kg for 15 days) respectively. The number of leukocytes and serum levels of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood, spleen index, and the function of NK cells were measured.

RESULTSCompared with the model group , SDCM increased the number of leukocytes and serum concentrations of IL-2, TNF-α and IFN-γ in peripheral blood and improved the spleen index and the function of NK cells significantly (P < 0.05-0.01).

CONCLUSIONSDCM could remarkably enhance the immune functions of immunosuppression mice induced by cyclophosphamide.

Animals ; Cyclophosphamide ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Immunosuppression ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Killer Cells, Natural ; immunology ; Mice ; Mice, Inbred BALB C ; Spleen ; immunology ; Tumor Necrosis Factor-alpha ; blood

Purpose of this study was to analyse the characteristics of clinical, iconographical, pathological and treatment methods of Langerhans cell histiocytosis (LCH), so as to improve the diagnosis and treatment level of this disease. The clinical data of 35 LCH patients were studied retrospectively. These patients were divided into 2 groups according to age <14 years old and ≥ 14 years old. The clinical symptoms were analysed and the signs, imageology and pathology manifestation and treatment results were evaluated. The results showed that LCH clinical manifestations were diverse and complex. Surgical treatment for patients with single system involvement of LCH was better than that of multi-system involvement of LCH (MS-LCH). For the latter, combined chemotherapy effects was better. After 3-year follow-up, 1-year OS was 94% ± 4%, 2-years OS was 91% ± 5%, 3-year OS was 86% ± 7%. 3 years OS of group <14 years old and ≥ 14 years old was 94% ± 6% and 81% ± 10% respectively. The OS of former was better than that of the later, but because a small number of cases, this difference was not statistically significant. It is concluded that LCH is easy to be misdiagnosed, the pathological biopsy is the gold standard of LCH diagnosis. The PET-CT can be of great help in identifying stages and finding lesion areas of the disease. Pulmonary Langerhans cell histiocytosis (PLCH) is more common in adult. Combined chemotherapy can improve the prognosis of the patients. The treatment methods should be choosed according to the stage and classification of disease.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Histiocytosis, Langerhans-Cell ; diagnosis ; drug therapy ; pathology ; Humans ; Infant ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo look for the active fraction of ethanol extract of Genkwa Flos (EGF) induced hepatotoxicity and develop an UPLC fingerprint of the active fraction.

METHODTarget fraction of EGF induced hepatotoxicity was guided by the serum biochemical and histopathology methods. The UPLC method was applied to establish the chromatographic fingerprint. The separation was achieved on a BEH C18 column (2.1 mm x 50 mm, 1.7 microm) with a mobile phase consisting of acetonitrile and water containing 0.05% phosphate acid running gradient elution. The detection was carried out at 210 nm and the analysis was finished within 10 min.

RESULTThe chloroform phase of EGF could be responsible for the hepatotoxicity of this herb. The common mode of the UPLC fingerprint was set up under the established condition. There were 17 common peaks in fourteen batches of herbs, eight of which were identified, and the similar degrees of the fourteen batches to the common mode were between 0.890-0.999.

CONCLUSIONIt is easy to locate the chloroform extraction of EGF with hepatotoxicity. And the UPLC fingerprint was developed for the above fraction, which could provide valuable references for safe and effective clinical use of EGF.

Animals ; Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; toxicity ; Flowers ; chemistry ; Humans ; Liver ; drug effects ; Male ; Rats ; Rats, Wistar