ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Objective To observe the clinical efficacy of Dan Qi Yishen Prescription in treating diabetic nephropathy(DN)and explore its renal protective mechanism.Methods A total of 150 patients with DN of qi-yin deficiency complicated with blood stasis syndrome who admitted to Sanya Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from October 2021 to April 2023 were divided into a control group and an observation group according to the random number table method,with 75 patients in each group.Both groups were given conventional therapies such as dietary treatment,blood glucose control,blood pressure control,lipid-lowering treatment and treatment of complications.Additionally,the control group was given intravenous injection of reduced glutathione,while the observation group was given oral use of the decoction of Dan Qi Yishen Prescription and ionic introduction of Dan Qi Yishen Prescription in renal region.Thirty days constituted one course of treatment,and both groups were treated for three courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,and the levels of renal function indicators,renal hemodynamic indicators,coagulation and fibrinolysis indicators,and vascular endothelial function indicators in the two groups were observed.Results(1)After treatment,the scores of TCM symptoms such as fatigue and weakness,palpitations and shortness of breath,dizziness and tinnitus,spontaneous sweating and night sweating,restlessness and insomnia,and thirst with preference for drinks in the two groups were decreased compared with those before treatment(P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(2)After treatment,the levels of renal function indicators such as blood urea nitrogen(BUN),serum creatinine(SCr),collagen Ⅳ(CⅣ),and plasma laminin(LN)of patients in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of renal hemodynamic indicators such as systolic maximum blood flow velocity(Vsmax)and diastolic minimum blood flow velocity(Vdmin)of the main renal artery(MRA)and interlobar artery(IRA)in the two groups were increased compared with those before treatment(P<0.05 or P<0.01),while the resistance index(RI)and pulsatility index(PI)of MRA and RI of IRA in the two group as well as PI of IRA in the observation group were decreased compared with those before treatment(P<0.05 or P<0.01).The increase of Vsmax and Vdmin of MRA and IRA as well as the decrease of RI and PI of MRA and IRA in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(4)After treatment,the levels of coagulation and fibrinolysis indicators such as prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),and fibrinogen(FIB)in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(5)The analysis of vascular endothelial function indicators showed that after treatment,the serum vasohibin 1(VASH-1)level in the two groups was increased compared with that before treatment(P<0.01),and the serum vascular endothelial growth factor(VEGF)and endothelin 1(ET-1)levels were decreased compared with those before treatment(P<0.01),and the increase of serum VASH-1 level as well as the decrease of serum VEGF and ET-1 levels in the observation group was significantly superior to that in the control group(P<0.01).Conclusion Dan Qi Yishen Prescription exerts good clinical efficacy in treating patients with DN of qi-yin deficiency complicated with blood stasis syndrome,and it has protective effect on renal function probably by improving the coagulation and fibrinolysis system and vascular endothelial function of the patients.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE To explore the willingness to pay （WTP） of Urumqi residents for community pharmacies’ medication guidance services and its influencing factors， so as to provide data support for the optimization of community pharmacy services and the establishment of a fee structure for medication guidance services. METHODS A stratified quota sampling method was employed to select 14 communities in Urumqi City. From April to June 2025， a combined offline and online questionnaire survey was conducted among adult residents in these communities. The contingent valuation method was used to construct three hypothetical scenarios （namely， basic， enhanced and extended services） of medication counselling in community pharmacies to assess residents’ WTP for these services. Binary Logistic regression was employed to analyze the influencing factors of WTP. RESULTS A total of 576 valid questionnaires were obtained. Under the scenarios of basic， enhanced and extended services， 38.54%， 49.65% and 67.19% of the respondents expressed WTP for the services， respectively. Occupational type， type of basic medical insurance， annual income， perception of pharmacists’ profession， and acceptance level of the service were identified as major influencing factors for WTP （P＜0.05）. CONCLUSIONS The willingness of residents in Urumqi to pay for medication counseling services provided by pharmacists in community pharmacies significantly increases with the enrichment of service content. It is recommended to incorporate basic medication counselling services provided by pharmacists in community pharmacies into medical insurance payment， while value-added services should be partially or fully self-paid by residents. Additionally， efforts should be made to strengthen the promotion of the professional and service value of licensed pharmacists， so as to facilitate the high-quality development of pharmaceutical care.

OBJECTIVE: To observe the effects of Tiaoshu Anshen (regulating the hinge and calming the mind) acupuncture on sleep quality and serum levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in patients with chronic insomnia. METHODS: A total of 58 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 29 cases in each group. Tiaoshu Anshen acupuncture was applied at Baihui (GV20) and bilateral Shenmen (HT7), Sanyinjiao (SP6), Benshen (GB13) in the acupuncture group, once a day, 1-day interval was taken after 6 consecutive days of treatment. Estazolam tablet was given orally before bed in the medication group, 1 mg each time. The 4-week treatment was required in both groups. Before and after treatment, the sleep quality was assessed by Pittsburgh sleep quality index (PSQI) and polysomnography (PSG), the serum levels of 5-HT and DA were detected by ELISA. RESULTS: After treatment, the item scores and total scores of PSQI were decreased compared with those before treatment in the two groups (P<0.05); in the acupuncture group, the scores of sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorders and total score of PSQI were lower than those in the medication group (P<0.05). After treatment, the total sleep time (TST) was prolonged (P<0.05), the sleep latency (SL) and wake after sleep onset (WASO) were shortened (P<0.05), the sleep efficiency (SE%), percentage of non-rapid eye movement stage 3 (N3%), percentage of rapid eye movement stage (REM%) and serum levels of 5-HT were increased (P<0.05) compared with those before treatment; the percentage of non-rapid eye movement stage 1 (N1%), percentage of non-rapid eye movement stage 2 (N2%) and serum levels of DA were decreased (P<0.05) compared with those before treatment in the two groups. After treatment, in the acupuncture group, TST was longer, while SL and WASO were shorter than those in the medication group (P<0.05), SE%, N3%, REM% and serum level of 5-HT were higher, while N1%, N2% and serum level of DA were lower than those in the medication group (P<0.05). CONCLUSION Tiaoshu Anshen acupuncture may improve the sleep quality by regulating the serum neurotransmitter levels i.e. 5-HT and DA in patients with chronic insomnia.
Humans ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Serotonin/blood* ; Sleep Quality ; Acupuncture Points ; Dopamine/blood* ; Aged ; Neurotransmitter Agents/blood* ; Young Adult

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.