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*

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: To compare the clinical efficacy between visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy (VPTED) and traditional percutaneous transforaminal endoscopic discectomy(PTED) in the treatment of lumbar disc herniation. METHODS: The clinical data of 60 patients with lumbar disc herniation admitted from June 2019 to December, 2020 was retrospectively analyzed. There were 38 males and 22 females, aged from 26 to 58 years old with an average of (43.63±8.48) years, 47 cases were on L_4,5 segment and 13 cases were on L₅S₁ segment. Among them, 32 were treated with VPTED (group A) and 28 were treated with traditional PTED (group B). The general conditions of all the patients were recorded, including intraoperative fluoroscopy times, operation time, hospital stay and surgical complications during follow-up. The arthroplasty area ratio was observed by sagittal CT at the middle level of the intervertebral foramen. Visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score of low back pain, Oswestry disability index (ODI) were used to evaluate the clinical efficacy between two groups. RESULTS: All patients were followed up from 9 to 15 months with an average of (12.10±1.16) months. There was no statistical difference of preoperative general data between two groups. The operation time, fluoroscopy times and hospital stay were (70.47±5.87) min, (13.66±1.34) times and (6.31±0.69) d in group A, and (90.71±7.66) min, (22.82±2.48) times and (6.54±0.92) d in group B. The operation time and intraoperative fluoroscopy times in group A were lower than those in group B(P<0.05). There was no significant difference in hospital stay between two groups (P>0.05). No obvious surgical complications were found during the follow-up in both groups. The arthroplasty area ratio in group A was (29.72±2.84)% and (29.57±2.20)% in group B, respectively, with no significant difference (P>0.05). There was no significant difference in VAS, ODI and JOA score between two groups before operation and at the final follow-up(P>0.05), but the final follow-up was significantly improved(P<0.05). CONCLUSION The two surgical methods have definite clinical efficacy in the treatment of lumbar disc herniation. Visual trephine arthroplasty assisted percutaneous transforaminal endoscopic discectomy has the advantages of high efficiency and rapidity when establishing the channel, and can significantly reduce the operation time and intraoperative fluoroscopy times.
Male ; Female ; Humans ; Adult ; Middle Aged ; Intervertebral Disc Displacement/surgery* ; Retrospective Studies ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Diskectomy, Percutaneous/methods* ; Diskectomy/methods* ; Treatment Outcome ; Arthroplasty

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

The present study comprehensively compared the content of chondroitin sulfate in Cervi Cornu Pantotrichum(CCP) and Cervi Cornu(CC) of different specifications and explored the feasibility of chondroitin sulfate as an indicator to distinguish between CCP and CC. Twenty-two batches of CCP of different specifications(two-branched velvet antler and three-branched velvet antler) from 15 habitats, CC from 6 habitats, and 60 batches of CCP slices prepared from different parts(wax slices, powder slices, gauze slices, and bone slices) were collected. High-performance liquid chromatography(HPLC) was used to determine chondroitin sulfate content in CCP and CC of different specifications. Cluster analysis was used to classify CCP slices of different specifications. The results showed that CCP contained abundant chondroitin sulfate. The average content of chondroitin sulfate was 2.35 mg·g~(-1) in two-branched velvet antler and 1.79 mg·g~(-1) in three-branched velvet antler, significantly higher than 0.11 mg·g~(-1) in CC. Chondroitin sulfate content in wax slices, powder slices, gauze slices, and bone slices were 7.81, 8.39, 1.33, and 0.54 mg·g~(-1), respectively. Cluster analysis showed that gauze slices and bone slices could be clustered into one category and distinguished from wax slices and powder slices. CCP slices prepared from different parts could be separated well through chondroitin sulfate content. Based on the five principles of Q-marker selection, chondroitin sulfate can be used as a potential Q-marker for the identification of CCP and CC, as well as a potential quality indicator for CCP slices of different specifications(wax slices, powder slices, gauze slices, and bone slices). This research provides data support for CCP quality evaluation.
Animals ; Cornus ; Chondroitin Sulfates ; Deer ; Powders ; Antlers ; Gastropoda

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.
Anti-Inflammatory Agents ; Biomarkers ; Drugs, Chinese Herbal ; Flavonoids ; Hippophae

Drynariae Rhizoma is warm in nature and bitter in taste, mainly acting on liver and kidney systems. It is a common Chinese herbal medicine for the treatment of fracture and bone injury. The chemical compositions of Drynariae Rhizoma mainly include flavonoids, triterpenoids, phenylpropanoids and lignans. At present, modern pharmacological and clinical studies have shown that Drynariae Rhizoma has the effects of anti osteoporosis, promoting fracture healing, kidney protection, anti-inflammatory, promoting tooth growth, preventing and treating aminoglycoside ototoxicity and lowering blood lipid. In addition, the toxicity evaluation experiment of Drynariae Rhizoma has also shown that it has no obvious toxic and side effects. Naringin is a kind of dihydroflavone in Drynariae Rhizoma. Many studies have shown that naringin and other total flavonoids play an important role in anti-osteoporosis, promoting fracture healing, anti-inflammation, promoting tooth growth and lowering blood lipid. In this study, the research progresses on chemical consti-tuents and pharmacological activities of Drynariae Rhizoma in recent years were reviewed, and some mechanisms of action were summarized, to provide references for the further research and development of Drynariae Rhizoma.
Drugs, Chinese Herbal/pharmacology* ; Flavonoids ; Humans ; Osteoporosis/drug therapy* ; Polypodiaceae ; Rhizome

Child ; Epiphyses ; Fracture Fixation, Internal ; Humans ; Lower Extremity

Antibodies, Viral ; blood ; Betacoronavirus ; immunology ; Coronavirus Infections ; diagnosis ; Gold Colloid ; chemistry ; Humans ; Immunoassay ; methods ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Pandemics ; Pneumonia, Viral ; diagnosis ; Reagent Kits, Diagnostic

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.