ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

Objective:To investigate the repair effect of bone marrow mesenchymal stem cells(BMSCs)on interferon gamma(IFN-γ)induced ovarian granulosa cell immune injury.Methods:A model of IFN-γ-induced ovarian granulosa cell immune injury was estab-lished.KGN cells after modeling were co-cultured with human BMSCs(hBMSCs)and divided into three groups:negative control(NC)group,IFN-γ group,and BMSC group.After co-culture,cell proliferation was determined by a cell counting kit 8 assay for 3 consecu-tive days.Cell apoptosis was determined using an Annexin V-FITC apoptosis detection kit and a CytoFLEX flow cytometer.The estra-diol level and the mRNA expression levels of aromatase CYP19A1 and FSHR were measured to evaluate the hormone synthesis ability.The level of lactate dehydrogenase(LDH),mRNA expression levels of NLRP3,caspase-1(CASP1),and interleukin-1β,and protein expression levels of NLRP3,CASP1,and gasdermin-D were determined to evaluate cell pyroptosis.Results:The proliferation rate of granulosa cells in the IFN-γ group and the BMSC group was lower than that in the NC group at 24 h,48 h and 72 h,and that in the IFN-γ group was lower than that in the BMSC group(P<0.001).The number of apoptotic granulosa cells in the INF-γ group and the BMSC group was higher than that in the NC group,and that in the INF-γ group was higher than that in the BMSC group(P<0.001).The estradiol level in the INF-γ group and the BMSC group was lower than that in the NC group,and that in the INF-γ group was lower than that in the BMSC group(P<0.001).Compared with the IFN-γ group,the mRNA expression of CYP19A1 and FSHR in the BMSC group decreased(P<0.001).Compared with the IFN-γ group,the BMSC group had significantly decreased LDH level,mRNA expression levels of NLRP3 and CASP1,and protein expres-sion level of CASP1.Conclusion:hBMSCs repair the immune in-jury of KGN cells induced by IFN-γ by restoring cell proliferation,inhibiting cell apoptosis,repairing endocrine function,and reducing pyroptosis.

ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth， the rats were randomly divided into blank （NC） group， maternal-infant separation （MS） group， restraint stress （RS） group， maternal-infant separation combined with restraint stress （MRS） group， Wenyang group， Jieyu group， Wenyang Jieyu （XSF） group， and minocycline group. Maternal-infant separation was performed on day 5 （PD5）， followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group， Xiaoyao group， XSF group and minocycline group were 5.85， 12.03， 16.71 g·kg^-1 and 50 mg·kg^-1， respectively. Restraint stress was applied on PD90. The model was evaluated using glucose， social interaction， open field， and O-maze behavior tests， as well as high-performance liquid chromatography to measure serotonin， dopamine， and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 （Iba-1） protein， a marker of hippocampal microglia， was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of M1 markers， JAK2/STAT3 pathway-related genes， and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group， the MRS group exhibited depression-like behavior， with significantly decreased levels of neurotransmitters in the hippocampus （P<0.05， P<0.01）， increased expression of Iba-1 （P<0.01）， and elevated protein levels of JAK2 and STAT3 （P<0.05）. The mRNA expression levels of CD68， CD11b， IL-1β， JAK2， and STAT3 were significantly increased （P<0.01）， while IL-10 mRNA expression was significantly decreased （P<0.01）. Compared with the MRS group， the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups， the hippocampal neurotransmitter content was significantly increased （P<0.05， P<0.01）， and Iba-1 expression was significantly decreased （P<0.01）. The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68， CD11b， JAK2， STAT3， and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups （P<0.05， P<0.01）， while IL-10 mRNA expression was significantly increased （P<0.05， P<0.01）. ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.

Objective To provide basis for the formation of acute exacerbation of chronic obstructive pulmonary disease(AECOPD-STES),the item weight of the syndrome therapeutic evaluation scale for AECOPD-STES was determined.Methods Based on the clinical survey data of 387 AECOPD patients,the random forest method was adopted,and the Spyder integrated development environment.Anaconda navigator software was used to call the"random forest Classifier"in the sklearn package to establish the initial random forest model and calculate the item weights.Factor analysis was used to extract common factors with cumulative variance contribution>80%,and the item weight was calculated according to the cumulative variance contribution and component score coefficient of common factors.The percentage weight method was used to calculate the item weight based on the importance score of each item by 29 experts.Finally,40%,30%and 30%of the above three methods were given respectively to determine the final weight of the items.Results The random forest method showed that the weights of wind cold syndrome,cold Yin syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.014-0.170,0.076-0.194,0.017-0.183,0.010-0.183 and 0.069-0.298,respectively.Factor analysis showed that the weights of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.030-0.111,0.100-0.182,0.037-0.095,0.022-0.141 and 0.054-0.185,respectively.The percentage weight method shows that the weight ranges of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.072-0.102,0.146-0.182,0.057-0.077,0.075-0.111 and 0.115-0.185,respectively.According to the three methods,the weights of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.050-0.121,0.117-0.174,0.040-0.117,0.056-0.130 and 0.092-0.188,respectively.Conclusion This study determined the weight of each item of AECOPD-STES,providing a basis for the calculation of syndrome score.

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Objective Exploring the clinical diagnosis and treatment status of epilepsy patients at the epilepsy specialty clinic in a single-center comprehensive hospital in the Lhasa area of the Tibetan Plateau.Methods Epilepsy patients who visited the epilepsy specialty clinic of the Department of Neurology at the Tibet Autonomous Region People's Hospital from September 2021 to June 2023 were continuously enrolled.Data such as clinical characteristics and diagnosis and treatment conditions of the enrolled patients was analyzed.Results A total of 121 patients were enrolled in this study,with 33.9%(41/121 cases)being new patients at our hospital and 6.6%(8/121 cases)being referred to our hospital.Non-adherence to treatment,with patients self-reducing or stopping medication without medical advice,accounted for 8.3%(10/121 cases)of the cases.The majority of epilepsy patients were in the young and middle-aged group,with 51.2%(62/121 cases)being between 18 and 44 years old.There were significant differences in the distribution of epilepsy patients across different age groups(P<0.001),while there was no significant difference in gender distribution(49.6%male vs.50.4%female,P>0.05).Generalized seizures were the predominant type of seizure(75.2%,91/121 cases),and 73.6%(89/121 cases)of the patients had an unknown etiology for their epilepsy,with symptomatic epilepsy accounting for 26.4%(32/121 cases)and structural causes being the most common at 24.8%(30/121 cases).Monotherapy was the main treatment for epilepsy(55.4%,67/121 cases),with sodium valproate being the most frequently prescribed drug for monotherapy at 22.3%(27/121 cases).Conclusion In the epilepsy specialty clinic in the plateau region,newly diagnosed patients account for about one-third,and over one-tenth of revisiting patients have not been receiving standardized treatment.The majority of our epilepsy patients are young to middle-aged adults.Generalized seizures are the predominant type.The etiology is unknown in the majority of cases,with structural causes being a common etiology in symptomatic epilepsy.Sodium valproate is the most frequently used antiseizure medication(ASM)in monotherapy in the plateau area.

Objective To study the application of mesoporous silica nanoparticle(MSN)as drug carriers in the treatment of osteoarthritis(OA).Methods Core-cone structured MSN(MSN-CC)was synthesized by sol-gel method,modified by polyethyleneimine(PEI),and loaded with hyaluronic acid synthase 2(HAS2).Forty OA model rats were randomly assigned to OA group,MSN-CC-PEI group,hyaluronic acid(HA)group,or MSN-CC-PEI-HAS2 group.Ten healthy rats were assigned to control group.Normal saline 100 μL was injected into the knee joint in the control group and OA group.MSN-CC-PEI 100 μL,HA solution 100 μL,and MSN-CC-PEI-HAS2 100 μL were injected in MSN-CC-PEI group,HA group,and MSN-CC-PEI-HAS2 group,respectively.The levels of HA,interleukin-1β(IL-1β),and prostaglandin E2(PGE2)in the joint effusion and the foot swelling degree were measured at 1,2,and 3 weeks after injection.Results HA level in the MSN-CC-PEI-HAS2 group was significantly lower than that in the HA group at 1 week after intervention(P<0.05),while HA level in the MSN-CC-PEI-HAS2 group was significantly higher than that in the HA group at 2 and 3 weeks after intervention(P<0.05).With the time going on,HA level in the HA group was gradually decreased(P<0.05),but HA level in the MSN-CC-PEI-HAS2 group was gradually increased(P<0.05).At 1 and 2 weeks after intervention,compared with the HA group,IL-1β,PGE2 and foot swelling degree in the MSN-CC-PEI-HAS2 group were increased(P<0.05).At 3 weeks after intervention,compared with the HA group,IL-1β,PGE2 and foot swelling degree in the MSN-CC-PEI-HAS2 group were decreased(P<0.05).With the time going on,IL-1β,PGE2 and foot swelling degree in the HA group and MSN-CC-PEI-HAS2 group were gradually decreased(P<0.05).Conclusion MSN carrier can stably stimulate the secretion of endogenous HA,reduce the inflammatory response within joint cavity of OA rats,and improve the joint morphology and soft tissue pathological changes.

Objective To construct a nursing registry platform for percutaneous coronary intervention(PCI)to provide data support for subsequent real-world research on PCI nursing.Methods From April to December 2023,we established a variable list and data dictionary based on literature review and expert discussion,and constructed a web-based PCI nursing registry platform based on registry-related standards.Results A total of 191 variables were screened in this study,and a corresponding data dictionary was developed for each variable according to the variable name,variable code,variable definition,variable type,variable value range,data source and data collection node.Three levels of account privileges has been set up in the platform,which can realize different data management privileges,and the data can be saved only after filling in and reviewing at each level.The platform is also equipped with automatic data checking function,which reduces data filling errors and improves data quality.Conclusion The constructed PCI nursing registration platform has strong scientific and professional characteristics,and can provide data support for subsequent research,and the content and functions of the platform can be further optimized in the future.