Objective To compare the clinical efficacy of ligament advanced reinforcement system(LARS)and autoge-nous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL).Methods A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admit-ted to our hospital between August 2019 and December 2021 were selected for complete follow-up.There were 78 males and 18 females,40 cases of left leg and 56 cases of right leg,the aged from 20 to 56 years old with an average of(32.50±8.68)years old.The transplants were divided into two groups:LARS group(52 cases)and autogenous hamstring tendon plus high-strength suture group(44 cases).In the LARS group,there were 42 males and 10 females;with an average age of(31.84±8.62)years old;body mass index(BMI)was(24.73±2.29)kg·m-2;7 mm LARS was used to reconstruct PCL.In the autologous tendon group,there were 36 males and 8 females,with an average age of(33.06±8.99)years old,BMI was(23.52±2.16)kg·m-2,and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture.All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation,and subjective evaluation of knee function by Lysholm score,Tegner score,and International Knee Documentation Council(IKDC)score.Data from preoperative,3,6,and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients.Results Ninety-six patients were followed up for 12 months.KT-1000 measurement of knee joint in autoge-nous tendon group and LARS group before operation[(10.73±1.46)points vs(10.55±1.53)points],6 months after operation[(3.02±0.75)points vs(2.35±0.60)points],12 months after operation[(3.77±1.76)points vs(2.44±0.60)points].There was significant difference between the two groups at 6 and 12 months after operation(P＜0.05),but there was no significant dif-ference between the two groups at 3 months after operation(P＞0.05).In the autogenous tendon group and LARS group,before operation and 12 months after operation,total Lysholm score[(40.6±16.8),(91.25±6.35)points vs(51.92±18.52),(92.35±5.30)points],Tegner score[(1.8±0.7),(5.8±0.6)points vs(1.7±0.8)、(5.7±0.7)points]and total IKDC score[(54.50±6.33),(83.90±3.93)points vs(54.40±4.24),(83.62±3.64)points],the differences were statistically significant(P＜0.05),indicating that the knee function of the two groups was improved after surgery.At 3 and 6 months after operation in the autoge-nous tendon group and LARS group,the total Lysholm score[(65.86±11.54),(74.60±6.46)points vs(73.46±6.42),(86.73±4.62)points],Tegner score[(2.5±0.6),(3.5±0.5)points vs(4.3±0.7),(5.0±1.4)points],the total scores of IKDC[(55.78±2.68),(70.62±4.74)points vs(65.31±4.60),(79.71±2.93)points].The difference between two groups was statistically sig-nificant(P＜0.05).The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group.However,at 12 months after the operation,there was no significant difference in the score of knee joint function between the two groups(P＞0.05).The results showed that the stability of LARS group was better than that of autologous tendon group.Conclusion Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability,with satisfactory postoperative results.Howervr the LARS provides superior postopera-tive stability.

AIM To investigate the protective effects of Didang Decoction-containing serum on rat glomerular endothelial cells(RGECs)following high glucose injury.METHODS Rats were given distilled water or Didang Decoction by gavage to prepare the blank serum or Didang Decoction-containing serum.CCK8 method was used to screen the glucose concentration for the modeling and serum concentration of the drug.The RGECs were divided into the blank group,the model group,Didang Decoction group(10%Didang Decoction medicated serum),Dapagliflozin group(normal serum+2 μmol/L Dapagliflozin)and Didang Decoction+Dapagliflozin group(10%Didang Decoction medicated serum+2 μmol/L Dapagliflozin).24 hrs after the drug treatment,the RGECs had their mRNA and protein expressions of Nrf2,HO-1 and NQO-1 detected by RT-qPCR method and Western blot method;their Nrf2 fluorescence expression detected by immunofluorescence method;and their SOD activity and MDA level detected by colorimetric method.RESULTS Compared with the blank group,the model group displayed decreased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.01),and increased MDA level(P＜0.01).Compared with the model group,the groups intervened with the drugs showed increased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.05,P＜0.01),and decreased MDA level(P＜0.01).CONCLUSION Didang Decoction-containing serum can protect RGECs from high glucose injury through activating the Nrf2 signaling pathway.

Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Objective To explore the effect and mechanism of hydroxysafflor yellow A(HSYA)on autophagy in bEnd.3 cells after oxygen-glucose deprivation(OGD).Methods The bEnd.3 cells were divided into normal group(conventional culture),model group(OGD model),HSYA group(OGD model+75 μmol·L-1 HSYA),3-methyladenine(3MA)group(5 mmol·L-1 3MA+OGD model)and 3 MA+HSYA group(5 mmol·L-1 3 MA+OGD model+75 μmol·L-1 HSYA).The level of apoptosis was determined by TUNEL fluorescence staining;Western blot was used to detect the expression of autophagy,blood brain barrier(BBB)related proteins;real time fluorescence quantitative polymerase chain reaction method for determining the expression of sirtuin-1(SIRT1)and forkhead box protein O3a(FOXO3A)mRNA.Results In the normal group,model group,HSYA group,3MA group and 3MA+HSYA group,the positive cells selected for TUNEL staining were 5.00±1.00,28.00±2.00,21.00±3.00,35.33±2.51 and 29.67±2.52;the expression levels of microtubule-associated protein 1 light chain 3-Ⅱ/-Ⅰ(LC3-Ⅱ/-Ⅰ)were 0.90±0.20,1.34±0.10,1.95±0.14,0.76±0.15 and 1.14±0.09;sequestosome 1(P62)were 0.99±0.02,0.60±0.02,0.38±0.01,0.67±0.04 and 0.54±0.01;occludin were 1.39±0.17,0.62±0.15,1.00±0.09,0.40±0.13 and 0.80±0.15;zonula occludens-1(ZO-1)were 1.63±0.20,0.64±0.06,0.98±0.14,0.37±0.14 and 0.87±0.04;SIRT1 mRNA were 1.00±0.00,0.75±0.07,1.69±0.09,0.31±0.02 and 0.56±0.01;FOXO3A mRNA were 1.00±0.00,0.80±0.05,1.47±0.09,0.40±0.01 and 0.62±0.09,respectively.Significant differences were found between model group and normal group,HSYA group and model group,3MA+HSYA group and 3MA group(P＜0.05,P＜0.01,P＜0.001).Conclusion HSYA may enhance autophagy levels in bEnd.3 cells after OGD through the SIRT1/FOXO3A pathway,inhibit cell apoptosis and alleviate BBB damage.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.