OBJECTIVE To systematically evaluate the efficacy of dydrogesterone combined with estradiol valerate for the prevention of intrauterine adhesion （IUA） and prognosis improvement after induced abortion. METHODS Retrieved from CNKI， Wanfang Data， VIP， CBM， PubMed， Embase and the Cochrane Library， randomized controlled trial （RCT） about conventional treatment combined with dydrogesterone and estradiol valerate （trial group） versus conventional treatment （control group） for the prevention of IUA in patients after induced abortion were collected from the inception to Dec. 2024. After screening the literature， extracting data and evaluating the quality of literature， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 RCTs were included， involving 1 109 patients. Meta-analysis showed that the postoperative incidence of IUA [RR＝0.30， 95%CI （0.22， 0.41）， P＜0.000 01]， postoperative vaginal bleeding time [MD＝－1.69， 95%CI （－2.05， －1.32）， P＜0.000 01]， postoperative vaginal bleeding volume [MD＝－10.78， 95%CI （－12.19， －9.37）， P＜0.000 01]， postoperative menstrual resumption time [MD＝－6.99， 95%CI （－8.27， －5.71）， P＜0.000 01]， and the incidence of postoperative reduced menstrual flow [RR＝0.25， 95%CI （0.12， 0.56）， P＝0.000 7] were significantly lower， less or shorter than control group； postoperative endometrial thickness [MD＝ 1.90， 95%CI （1.68， 2.13）， P＜0.000 01] and the rate of postoperative re-pregnancy [RR＝6.26， 95%CI （1.88， 20.83）， P＝0.003] were significantly higher than control group. CONCLUSIONS Dydrogesterone combined with estradiol valerate may reduce the incidence of IUA after induced abortion patients， decrease postoperative vaginal bleeding volume， shorten postoperative vaginal bleeding time and postoperative menstrual resumption time， and increase postoperative endometrial thickness.

ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties， the chemical components of Sojae Semen Nigrum（SSN） and Sojae Semen Praeparatum（SSP） were systematically compared and analyzed， and the main fermentation products in different fermentation time were quantitatively analyzed， so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the structural identification of the chemical constituents of SSN and SSP， and with the aid of Progenesis QI v2.3 software， the negative ion mode was employed for principal component analysis（PCA） pattern recognition， and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis（OPLS-DA） for two-dimensional data to obtain S-plot， and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC， and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period， and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate（PITC） pre-column derivatization and high performance liquid chromatography（HPLC） gradient elution， and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value（TAV）. ResultA total of 19 kinds of differential components were screened out， mainly soybean saponins and isoflavones， and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP， glycoside bond hydrolysis mainly occurred， and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones， the content of flavor substances such as amino acids increased gradually. In the post-fermentation process， protein degradation mainly occurred， after 8 d of post-fermentation， the content of isoflavones was basically stable， while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP， such as the TAV of glutamate is always ahead of other flavor substances， and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation， combined with the traditional evaluation index of "fragrant and strong"， it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant， delicious and slightly sweet"， and at the same time， the post-fermentation index compounds such as glutamic acid， alanine and valine should be added as the quality control indicators of SSP， so as to standardize the production process and improve the quality of SSP.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

Intracerebral hemorrhage(ICH)is a nervous system disease that seriously endangers human health,with a very high rate of disability and fatality.Most survivors will leave behind varying degrees of neu-rological dysfunction.Therefore,early assessment of neurological function in the patients with cerebral hemor-rhage has an important clinical significance.Diffusion tensor imaging(DTI)is a nuclear magnetic resonance technique to noninvasively reconstruct the structure and path of nerve fiber bundles in vivo,which can be used to the condition evaluation and prognosis judgment after ICH,and has an important clinical significance for the evaluation of neurological dysfunction.This paper reviews the related value of DTI in the prognosis evaluation of the patients with ICH.

Objective To study the correlation between single nucleotide polymorphisms at loci rs4535211,rs75885714,and rs7653834 of phosphatidylinositol-specific phospholipase 2 (PLCL2) gene and large artery atherosclerotic (LAA) ischemic stroke.Methods A total of 105 patients with newly diagnosed LAA ischemic stroke admitted to the Second Affiliated Hospital of Xinjiang Medical University from July 2021 to July 2022 were selected as the observation group,and 103 patients with gender and age matching phys-ical examination in this hospital during the same period were selected as the control group. The clinical data and serum inflammatory markers were collected and compared between the two groups.Genotypes of PLCL2 gene rs4535211,rs75885714 and rs7653834 loci in the two groups were detected,and genotype and allele fre-quencies were calculated.Results The levels of C-reactive protein (CRP),interleukin-6 (IL-6),neutrophil to lymphocyte ratio (NLR),monocyte to high-density lipoprotein-cholesterol ratio (MHR),platelet to lympho-cyte ratio (PLR) and D-dimer in the observation group were higher than those in the control group.The level of high density lipoprotein-cholesterol (HDL-C) was lower than that of the control group (P<0.05). rs7653834 locus was C/C,C/T,T/T genotypes,and the difference between the two groups was statistically significant (P<0.05).The levels of C/C,T/C and T/T genotypes NLR and PLR at rs7653834 locus were sta-tistically significant between the two groups (P<0.05).The analysis results of co-dominant model,dominant model and overdominant model showed that there was statistical significance in rs7653834 locus genotype be-tween the two groups (P<0.05).Conclusion There may be a potential association between rs7653834 locus polymorphism of PLCL2 gene and LAA type ischemic stroke.

Gag-Pol protein is one of the important structural proteins of human immunodeficiency virus(HIV),comprising the basic scaffold proteins and functional enzymes required during the lifecycle of HIV.Currently,the inhibitors targeting different functional domains on Gag-Pol include capsid(CA)inhibitors,protease inhibitors,reverse transcriptase inhibitors,and integrase inhibitors.The CA inhibitors inhibit the maturation of CA or disrupt the assembly of CA,so as to affect the replication of HIV.The primary mechanism of protease inhibitors is to inhibit the protease from cleaving at the cleavage site CA-spacer peptide 1(SP1).The reverse transcriptase inhibitors block the reverse transcription process of HIV by mimicking the reverse transcription substrates.The integrase inhibitors impact the activity of integrase by targeting the zinc-finger structure at the active center of integrase.This article summarizes the inhibitors targeting HIV Gag-Pol protein and their mechanisms,and reviews the approved dosages and usages of approved patent drugs,so as to provide the references for the future clinical combination therapies and the development of new inhibitors targeting HIV Gag-Pol protein.

Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P＞0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P＜0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P＜0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P＜0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P＜0.01),the expression level of γH2AX(P＜0.05),and the ROS level(P＜0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P＜0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P＜0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P＜0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P＜0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P＜0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P＜0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P＜0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

Objective:To investigate the correlation between blood lipid variability and recurrence of cerebrovascular events in patients with ischemic stroke.Methods:Patients with ischemic stroke admitted to Qingdao Municipal Hospital from June 1, 2020 to December 31, 2022 were prospectively enrolled and followed up for 30 months. The standard deviation (SD) and coefficient of variation (CV) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were calculated during follow-up, and the attainment rate of blood lipid before and after follow-up were compared. The recurrence of cerebrovascular events was monitored, including ischemic stroke, cerebral hemorrhage, and transient ischemic attack. Cox proportional hazards regression model was used to analyze the correlation between the variability of TC, LDL-C, HDL-C, and TG and the recurrence of cerebrovascular events.Results:A total of 142 patients with ischemic stroke were enrolled, including 81 males (57.0%), aged 63.4±5.8 years. During follow-up, 34 patients (23.9%) experienced recurrent cerebrovascular events. At the end of the follow-up, TC, TG, and LDL-C levels decreased significantly compared to before the follow-up (all P<0.05), and the attainment rate of blood lipid increased significantly compared to before the follow-up (51.4% vs. 12.7%; P=0.001). CV of LDL-C in the recurrent group was significantly higher than that in the non-recurrent group ( P=0.005). Cox proportional hazards regression analysis showed that after adjusting for age, gender, body mass index, baseline blood lipids, and baseline blood pressure, LDL-C variability (SD: hazard risk [ HR] 4.051, 95% confidence interval [ CI] 2.671-5.687, P=0.034; CV: HR 3.785, 95% CI 2.356-5.013, P=0.041) and TC variability (SD: HR 3.821, 95% CI 2.450-5.224, P=0.039; CV: HR 3.715, 95% CI 2.401-5.036, P=0.042) during follow-up were independently associated with the recurrence of cerebral vascular events. Conclusions:LDL-C and TC variability are the independent influencing factors for the recurrence of cerebrovascular events in patients with ischemic stroke. Monitoring the variability of LDL-C and TC in patients with ischemic stroke and intervening in a timely manner may reduce the risk of recurrence of cerebrovascular events.

Objective To analyze the risk factors of lower limb deep vein thrombosis(DVT)after the closed Pilon fracture surgery,and to build a nomograph prediction model.Methods A total of 182 patients with closed Pilon fracture who underwent surgical treatment in our hospital from June 2019 to June 2022 were retrospectively analyzed,according to the occurrence of postoperative DVT,the patients were divided into two groups:43 cases in DVT group and 139 cases in non-DVT group.Univariate and multivariate Logistic regression analysis was applied to screen the risk factors of lower limb DVT after closed Pilon fracture surgery;R software was applied to build a nomograph model for predicting lower limb DVT after closed Pilon fracture surgery,and receiver operating characteristic(ROC)and calibration curve were applied to verify the nomograph model.Results Logistic regression analysis showed that the history of diabetes mellitus,risk assessment of thrombosis as medium and high risk,and postoperative infection were independent risk factors for lower limb DVT after closed Pilon fracture surgery(P＜0.05).The area under the ROC curve was 0.716(95％CI:0.629-0.804).The slope of calibration curve was close to 1,and H-L goodness of fit test x2=2.556,P=0.635.Conclusion The history of diabetes,the result of thrombosis risk assessment as"medium-high risk",and the postoperative infection occurred at the surgical site are independent risk factors for lower limb DVT after closed Pilon fracture surgery.The nomogram prediction model constructed by integrating the above three independent risk factors can effectively predict lower limb DVT after closed Pilon fracture surgery,with high differentiation and consistency.

Objective Exploring the clinical application value of long chain non-coding RNA(lncRNA)H19 in peripheral blood mononuclear cells(PBMCs)in type 2 diabetes mellitus(T2DM)patients with osteoporosis(OP).Methods A total of 176 patients with T2DM admitted to the Department of Endocrinology of the First People's Hospital of Lianyungang City from December 2022 to June 2023 were selected.They were divided into OP group(n=100)and simple T2DM group(n=76)according to the results of bone mineral density(BMD)determination by dual-energy X-ray.General data and biochemical indicators were compared between the two groups.The correlation between lncRNA H19 and other clinical indicators was analyzed by Spearman correlation analysis and the influencing factors for T2DM with OP were analyzed by logistic regression.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of lncRNA H19 in T2DM with OP.Results Compared with T2DM group,the proportion of females,age,HbA1c,TC and TGF-β1 were higher(P<0.05),while BMI,SUA,BMD and lncRNA H19 were lower in OP group(P<0.05).Spearman correlation analysis showed that lncRNA H19 expression level was positively correlated with BMI,SUA and BMD(P<0.05),and negatively correlated with age,HbA1c and TGF-β1(P<0.05).Logistic regression analysis showed that age,BMI,TC,TGF-β1 and lncRNA H19 were the influencing factors for T2DM combined with OP(P<0.05).ROC curve analysis showed that the AUC of lncRNA H19 in the diagnosis of T2DM with OP was 0.839,the sensitivity was 76.3%,and the specificity was 86.0%.Multiple linear regression analysis showed that age,TGF-β1 and OP were the influencing factors for lncRNA H19(P<0.05).Conclusion LncRNA H19 expression decreased in PBMCs in patients with T2DM with OP,which may participate in the occurrence and development of T2DM with OP through glucose metabolism and lncRNA H19/TGF-β1 pathway.