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.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Objective:To explore the clinical manifestations,diagnosis,pathological features and treatment of small-cell carci-noma of the prostate(SCCP).Methods:We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018,and reviewed relevant literature.Results:Both the patients had the symptoms of frequent,urgent and difficult urination,with an elevated level of PSA and grades Ⅱ-Ⅲ enlargement of the prostate at palpation.One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor.Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases.One of them was treated by eto-poside-platinum(EP)chemotherapy and died of systemic multiple organ failure 20 months after diagnosis,while the other underwent endocrine therapy and has lived with tumor up to the present day.Conclusion:The incidence rate of SCCP is low,its malignancy is high,and its prognosis is poor.The average survival of the patient is about 7 to 10 months after diagnosis.Currently there is no effec-tive management of the dissease,except by relying on the experience of the treatment of small-cell lung cancer,with chemotherapy as the main option.

Objective To investigate the effect of hemoperfusion combined with sequential hemodiafiltration on pancreatic islet β cell function,nutritional status and inflammatory response in patients with diabetic nephropathy(DN).Methods One hundred patients with DN admitted to Nanyang Central Hospital from February 2022 to February 2023 were selected as the research subjects.They were divided into the control group and the observation group according to the random number table method,with 50 patients in each group.The patients in the control group were treated with sequential hemodiafil-tration,and the patients in the observation group were treated with sequential hemodiafiltration combined with hemoperfusion.The weight and height of patients in the two groups were measured before treatment and after 6-month treatment to calculate body mass index(BMI).The triceps skinfold(TSF)thickness was measured by using a skinfold caliper.The nutritional status of patients were evaluated by subjective global assessment(SCA)scores.Fasting venous blood was collected from patients in the two groups to measure the levels of fasting insulin(FINS)and fasting plasma glucose(FPG)by radioimmunoassay,and the homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment of beta-cell function(HOMA-β)were calculated;the levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were measured by using the fully automatic biochemical analyzer,and the levels of serum C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured by using the enzyme-linked immunosorbent assay.Results There was no significant difference in HOMA-β,FINS and HOMA-IR of patients between the control group and the observation group before treatment(P＞0.05).FINS and HOMA-IR of patients after treatment were significantly lower than those before treatment,while HOMA-β was significantly higher than that before treatment in the two groups(P＜0.05).After treatment,FINS and HOMA-IR of patients in the observation group were significantly lower than those in the control group,while HOMA-β was significantly higher than that in the control group(P＜0.05).There was no significant difference in BMI,TSF and SGA of patients between the control group and the observation group before treatment(P＞0.05).After treatment,BMI,TSF and SGA of patients in both groups were significantly higher than those before treatment;and BMI,TSF and SGA of patients in the observation group were significantly higher than those in the control group(P＜0.05).There was no significant difference in the levels of TC,TG,LDL-C and HDL-C of patients between the control group and the observation group before treatment(P＞0.05).After treatment,the levels of TC,TG and LDL-C of patients in both groups were significantly lower than those before treatment,while the HDL-C level of patients was significantly higher than that before treatment(P＜0.05).After treatment,the levels of TC,TG and LDL-C of patients in the observation group were significantly lower than those in the control group,while the HDL-C level of patients was significantly higher than that in the control group(P＜0.05).There was no significant difference in the levels of serum CRP,TNF-α and IL-6 of patients between the control group and the observation group before treatment(P＞0.05).After treatment,the levels of serum CRP,TNF-α and IL-6 of patients in both groups were significantly lower than those before treatment;and the levels of serum CRP,TNF-α and IL-6 of patients in the observation group were significantly lower than those in the control group(P＜0.05).Conclusion Sequential hemodiafiltration combined with hemoperfusion can significantly improve pancreatic islet βcell function,nutritional status and lipid metabolism in patients with DN and inhibit inflammatory response.

Objective To clarify the understanding of types of laboratories and manufacturers for GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance by laboratory proficiency testing for creepage distance and electrical clearance test.Methods An operation guide was formed according to the testing program in GB 9706.1-2020,and the homogeneity and stability of the samples were evaluated according to CNAS-GL003:2018 Guidance on Evaluating the Homogenneity and Stability of Samples Used for Proficiency Testing.Robust statistic methods were used to assess the quantitative parameters of the test results of the participating laboratories according to the requirements in GB/T 28043-2019 Statistical methods for use in proficiency testing by interlaboratory comparison;the results reported by the expert laboratories were used as the specified values of the qualitative parameters.SPSS 25.0 statistical software was used for data analysis.Results All the results of the crreepage distance and electrical clearance tests met the requirements for homogeneity and stability.Of the 46 laboratories involved in,37 ones did have comprehensive satisfactory determinations while the remained 9 ones not.Conclusion Some laboratories don't behave well in understanding the standard,which have to be reformed accordingly to enhance their proficiencies.[Chinese Medical Equipment Journal,2024,45(10):54-59]

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Adenomyosis(AM)is characterized by the benign invasion of endometrial tissue and stroma into the myometrium,resulting in diffuse or localized pathological changes.Typical symptoms include increased menstrual volume,prolonged menstrual periods,and progressive dysmenorrhea.In severe cases,AM can lead to infertility.Endometrial receptivity(ER)plays a crucial role in facilitating adhesion,penetration,and implantation required for successful embryo implantation and pregnancy outcome.The impairment of ER due to AM-related factors involves complex mechanisms.This article aims to provide a comprehensive review of recent research findings on the mecha-nisms underlying ER injury caused by AM over the past three years while highlighting the latest advancements in treatment strategies.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]