Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.

Opium is obtained by air-drying the milky latex extracted from the unripe capsules of the opium poppy(Papaver somniferum).This latex is rich in benzylisoquinoline alkaloids(BIA),with major active compounds in-cluding morphine,codeine,thebaine,papaverine,and noscapine.Compound licorice oral solution and compound licorice tablets are derivative drugs containing opium.Initially classified as over-the-counter(OTC)medications,both formulations were later reclassified as prescription drugs by the National Medical Products Administration(NMPA),restricting their purchase without proper authorization.Although the national pharmacopeia standards specify the morphine content in the opium raw materials used for compound licorice oral solution and tablets,they lack mandatory requirements for the detection and quantification of the other four major alkaloids.Given the unique nature of opium raw materials and the stringent regulatory requirements for such drugs,it is imperative to enhance and refine simultaneous detection and control methods for all alkaloid components in these products.Furthermore,the establishment of scientific and reasonable detection and control standards for preservatives in compound licorice formulations is crucial to improving overall product quality management and ensuring drug safety and efficacy.This study analyzes and discusses the quality standards,detection methods,and research progress for opium and com-pound licorice preparations,aiming to explore the potential for technological innovation and ensure the safe use of these medications.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.

Objective The results of ASTRUM-007 reveal the clinical benefits of PD-L1-positive esophageal squamous cell carcinoma(ESCC)patients.This study aims to analyze the economics of first-line treatment of PD-L1-positive ESCC with brucella combined with chemotherapy from the perspective of China's health system.Methods A three-state partitioned survival model(PSM)including progression-free survival(PFS),disease progression(PD),and death(D)was established to evaluate the economy of serplulimab combined with chemotherapy,the first-line treatment for PD-L1 positive advanced ESCC,compared with the placebo combination chemotherapy.The cycle period was two weeks,the horizon of the simulation was a lifetime,and the annual discount rate was set to 5%.The main outcome parameters are total cost,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).One-way sensitivity analysis(OWSA),probability sensitivity analysis(PSA),and scenario analysis were used to evaluate the impact of the change of important parameters in the model on ICER.Results The basic results showed that the incremental effect and incremental cost of the serplulimab combined with chemotherapy compared with the placebo combination chemotherapy were 1.281 QALYs and 266 573.26 yuan,respectively,and the ICER was 208 166.24 yuan/QALY.OWSA showed that the price of serplulimab was the most sensitive parameter to ICER;PSA showed that when the WTP threshold was three times China's per capita GDP in 2022,Serplulimab combined with chemotherapy was significantly more economical than the placebo combination chemotherapy;scenario analysis revealed that according to the ASTRUM-007 study in the Central Asian group and the charitable drug donation program of serplulimab:in patients with PD-L1 1≤CPS<10,ICER was 205 056.83 yuan/QALY;with 218 022.59/QALY in patients with PD-L1 CPS≥10,and the mean value of ICER was lower than three times of China's per capita GDP.The ICER of all patients was 59 046.65 yuan/QALY,with 68 294.42 yuan/QALY of patients with PD-L1 1≤CPS<10,44 744.02 yuan/QALY of patients with PD-L1 CPS≥10.The ICER value was lower than China's per capita GDP.Conclusion Serplulimab combined with chemotherapy is more economical than placebo combined with chemotherapy in the treatment of PD-L1-positive ESCC patients.

ObjectiveTo evaluate the therapeutic effect of stewed Polygoni Multiflori Radix on androgenic alopecia （AGA） and study the treatment mechanism. MethodNinety-nine SPF-grade male C57BL/6J mice were randomized into control， model， positive drug （finasteride， 0.65 mg·kg^-1）， low （0.78 g·kg^-1）， medium （1.56 g·kg^-1）， and high （3.12 g·kg^-1）-dose stewed Polygoni Multiflori Radix， and Polygoni Multiflori Radix Praeparata groups by the random number table method. The mouse model of AGA was constructed by subcutaneous multi-point injection of testosterone propionate diluent for 60 days， and the mice were administrated with corresponding drugs by gavage from day 11. The therapeutic effects of stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata on AGA were evaluated by newly hair area， hair length， hair weight in the hair removal area， and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to determine the levels of testosterone （T）， dihydrotestosterone （DHT）， and 5α-reductase （5-AR） in the skin tissue of mice. Western blot was employed to determine the expression levels of key proteins in the Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group （after 60 days of modeling） showed reductions in the newly hair area， hair length and weight in the back hair removal area， and ratio of hair follicles containing melanin to total hair follicles （P<0.05， P<0.01）， elevated levels of T， DHT， and 5-AR， up-regulated expression level of glycogen synthase kinase-3β （GSK-3β） （P<0.05， P<0.01）， and down-regulated expression levels of β-catenin， phospho-glycogen synthase kinase-3β （p-GSK-3β）， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue. Compared with the model group， the positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low-， medium-， and high-dose Polygoni Multiflori Radix Praeparata improved the newly hair area and hair length of mice （P<0.01）， and stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata at low and medium doses improved the weight of newly formed hair in mice （P<0.05， P<0.01）. The positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low- and high-dose Polygoni Multiflori Radix Praeparata increased the ratio of hair follicles containing melanin to total hair follicles in the skin tissue （P<0.05， P<0.01）. Compared with Polygoni Multiflori Radix Praeparata at the same doses， the medium and high doses of stewed Polygoni Multiflori Radix increased the ratio of melanin-containing hair follicles to total hair follicles （P<0.05）. Compared with the model group， stewed Polygoni Multiflori Radix lowered the levels of T and DHT， down-regulated the expression level of GSK-3β （P<0.01）， and up-regulated the expression levels of β-catenin， p-GSK-3β， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue of the mice. ConclusionStewed Polygoni Multiflori Radix can ameliorate androgenic alopecia in mice by reducing the androgen level and promoting Wnt/β-catenin signaling.

AIM:To investigate the improvement effect of blood flow-limited resistance training on renal fibro-sis in type 2 diabetes mellitus(T2DM)rats and its potential mechanism to attenuate renal fibrosis by inhibiting the trans-forming growth factor β1(TGF-β1)/Smad3 signaling pathway.METHODS:The T2DM model was prepared by combining a high-fat diet and streptozotocin(STZ),and after successful modeling,the rats were randomly divided into a T2DM con-trol group,a low-load resistance training group,a high-load resistance training group,a blood flow restriction group and a blood flow restriction combined with resistance training group for 8 weeks of exercise.The renal index,fasting blood glu-cose(FBG),serum creatinine(SCr),and blood urea nitrogen(BNU)were recorded in each group.The morphological changes of the kidneys were observed by hematoxylin and eosin(HE)and Masson's trichrome staining,and the collagen volume fraction was calculated.The mRNA expression levels of renal Klotho,TGF-β1,and α-smooth muscle actin(α-SMA)were detected by RT-qPCR.The protein expression levels of renal Klotho,TGF-β1,Smad3,phosphorylated Smad3(p-Smad3),α-SMA and connective tissue growth factor(CTGF)were detected using Western blot.RESULTS:Compared with the other groups,FBG,SCr,BNU,and renal collagen volume fraction were significantly decreased in the blood flow restriction combined with resistance training group of rats(P<0.05),Klotho expression was significantly in-creased(P<0.05),and the expression of TGF-β1,p-Smad3,CTGF and α-SMA was significantly decreased(P<0.05),and there was no significant change in the expression level of Smad3(P>0.05).CONCLUSION:Blood flow restriction combined with resistance training attenuates renal fibrosis in T2DM rats,the mechanism of which may be related to the up-regulation of Klotho expression,disruption of the TGF-β1/Smad3 signaling pathway,and inhibition of the deposition of epi-thelial-mesenchymal transformation.

Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (P < 0.05). No significant difference in serum FABP4 levels was found among the three groups (P>0.05). The levels of serum parathyroid hormone (PTH), alkaline phosphatase (ALP), type Ⅰ procollagen amino-terminal propeptide (PⅠNP), type Ⅰ collagen cross-linked C-terminal peptide (CTXⅠ), and bone-specific alkaline phosphatase (BALP) in the OP group were higher than those in the ON group and the normal bone mass group (P < 0.05). Lumbar post-menopause BMD was positively correlated with serum Apelin-13 levels (P < 0.05), but had no correlation with serum FABP4 levels (P>0.05). Lumbar BMD was negatively correlated with serum PTH, ALP, PⅠNP, CTXⅠ, BALP, and age (P < 0.05), but positively correlated with body weight, body mass index, T-score, fasting insulin, and insulin resistance index (P < 0.05). Multivariate Logistic regression analysis showed that serum Apelin-13, PTH, ALP, PⅠNP, CTXⅠ, and BALP levels were independent factors influencing the occurrence of OP in postmenopausal women (P < 0.05). ROC curve results showed that the optimal cut-off value of serum Apelin-13 for predicting PMOP was 18.51 pg/mL, with an area under the curve of 0.716, a sensitivity of 70.0%, and a specificity of 64.4%. Conclusion Apelin-13 is lowly expressed in the serum of PMOP patients, and its expression level is closely related to lumbar BMD, which may serve as an early screening indicator and potential therapeutic target for PMOP.

Objective To investigate the characteristics of the pathogens isolated from the specimens of tumor patients and detection rates of multidrug-resistant bacteria in a hospital in the past five years,so as to provide references for infection prevention and control.Methods The results of pathogenic culture and in vitro susceptibility of the strains isolated from the specimens collected between January 2019 and December 2023 from tumor patients were retrospectively collected,and the trends of the data were analyzed and summarized.Results A total of 16393 strains were isolated from 80386 specimens,producing a detection rate of 20.4％.After excluding the duplicate strains isolated from the same patients,Escherichia coli(14.5％),Klebsiella pneumoniae(13.2％),Staphylococcus aureus(9.4％),Acinetobacter baumannii complex(9.3％),and Pseudomonas aeruginosa(7.7％)predominated the 7951(81.1％)bacterial strains.Among the 1 857(18.9％)fungal strains,Candida albicans(56.5％),Candida tropicalis(9.0％),and Candida parapsilosis(8.0％)were the most common ones.The specimen sources differed among the prevalent species,and the species distribution varied among specimens from different types of tumors(P＜0.05).The detection rates of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae were 2.5％(29/1 152)and 12.3％(129/1050),respectively.The detection rate of methicillin-resistant Staphylococcus aureus was 22.0％(165/749),maintaining an upward trend in the last four years(P＜0.01).The detection rates of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa were 40.3％(298/739)and 8.8％(54/612),respectively.Conclusion Gram-negative bacteria were the prevalent pathogens of tumor patients.The detection rate of multidrug-resistant bacteria was relatively high,and the detection rate of methicillin-resistant Staphylococcus aureus showed an upward trend.

Objective:To construct a risk prediction model for infection with Klebsiella pneumonia (KP) for patients with severe acute pancreatitis (SAP).Methods:Retrospective analysis was done on the clinical data of 109 SAP patients who were admitted to Shanghai General Hospital, between March 2016 and December 2021. Patients were classified into infection group ( n=25) and non-infection group ( n=84) based on the presence or absence of KP infection, and the clinical characteristics of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension of the variables with statistical significance in univariate analysis. A nomogram prediction model was created by incorporating the optimized features from the LASSO regression model into the multivariate logistic regression analysis. Receiver operating characteristic curve (ROC) was drawn and the area under curve (AUC) was calculated; and consistency index (C-index) were used to assess the prediction model's diagnostic ability. Results:A total of 25 strains of KP were isolated from 109 patients with SAP, of which 21(84.0%) had multi-drug resistance. 20 risk factors (SOFA score, APACHEⅡ score, Ranson score, MCTSI score, mechanical ventilation time, fasting time, duration of indwelling of the peritoneal drainage tube, duration of deep vein indwelling, number of invasive procedures, without or with surgical intervention, without or with endoscopic retrograde cholangiopancreatography (ERCP), types of high-level antibiotics used, digestion disorders, abnormalities in blood coagulation, metabolic acidosis, pancreatic necrosis, intra-abdominal hemorrhage, intra-abdominal hypertension, length of ICU stay and total length of hospital stay) were found to be associated with KP infection in SAP patients by univariate analysis. The four variables (APACHEⅡ score, duration of indwelling of the peritoneal drainage tube, types of high-level antibiotics used, and total length of hospital stay) were extracted after reduced by LASSO regression. These four variables were found to be risk factors for KP infection in SAP patients by multiple logistic regression analysis (all P value <0.05). Nomogram prediction model for KP infection in SAP was established based on the four variables above. The verification results of the model showed that the C-index of the model was 0.939, and the AUC was 0.939 (95% CI 0.888-0.991), indicating that the nomogram model had relatively accurate prediction ability. Conclusions:This prediction model establishes integrated the basic clinical data of patients, which could facilitate the risk prediction for KP infection in patients with SAP and thus help to formulate better therapeutic plans for patients.

Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.