AIM: To observe the changes of corneal densitometry(CD)and higher-order aberrations after small incision lenticule extraction(SMILE), and to explore their correlations and influencing factors.METHODS: Prospective study. A total of 62 high-degree myopia and compound myopic astigmatism patients(62 eyes)who underwent SMILE in Urumqi Aier Eye Hospital from December 2022 to November 2023 were collected. The CD, root mean square of corneal higher-order aberrations(RMS HOA), spherical aberration, vertical coma, horizontal coma, and corneal epithelial thickness(CET)of the patients were measured before surgery, and at 1 d, 1 wk, 1, 3, and 6 mo after surgery, respectively.RESULTS:There were 4 patients lost to follow-up during the period, all due to failure to attend scheduled reexaminations. The number of complete and valid cases was 58 eyes. The CD in the central and paracentral regions of the anterior, middle, and total layer of the cornea increased significantly on the first day after surgery(all P<0.003). At 6 mo after surgery, there was a slight but statistically significant decrease in the CD of the central and paracentral regions of the anterior and the total anterior layer(all P<0.003). Compared with the preoperative baseline values, the RMS HOA, spherical aberration, and vertical coma significantly increased at 6 mo after surgery(all P<0.003), while the change in horizontal coma was not statistically significant. Compared with the preoperative baseline values, the CET in the central, paracentral, and peripheral regions of the cornea, as well as the total average CET in the 0-7 mm range of the cornea increased at 6 mo after surgery(all P<0.003). At 1 d after surgery, CD of the anterior layer and total layer in the central region of the cornea were positively correlated with the CET in the central region(rs=0.327, rs=0.250, all P<0.05). At 6 mo after the surgery, the CD of the middle layer and posterior layer in the central corneal region were negatively correlated with the preoperative spherical equivalent and the change of RMS HOA(all P<0.05).CONCLUSION:The anterior CD decreases at 6 mo after SMILE for high myopia correction, and there is a certain correlation between the changes in CD and some clinical parameters.

OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

Aim To explore the antimicrobial activity of a novel R-type phage tail-like bacteriocin(PTLB)secreted by Enterobacter cloacae SHAMU191747 a-gainst methicillin-resistant Staphylococcus aureus(MR-SA).Methods Antagonistic activity of E.cloacae SHAMU191747 against MRS A was detected by LB agar plate antagonistic test and LB broth micro-fermentation test.The crude extract of fermentation supernatant of E.cloacae SHAMU191747 was prepared by ultra-high-speed centrifugation and density gradient centrifuga-tion.The novel R-type PTLB in the crude extract was detected by transmission electron microscopy.The an-timicrobial activity of the crude extract against MRSA was verified by LB agar plate spot-seeding method.The molecular weight of the novel R-type PTLB was detected by SDS-PAGE electrophoresis.Results E.cloacae SHAMU191747 secreted a novel R-type PTLB,and had a strong antagonistic effect on MRSA.The no-vel R-type PTLB had a molecular weight of approxi-mately 35 ku and could efficiently kill MRSA.The physical dimensions of its tail-sheath-uncontracted functional molecules were(142.7±4.3)×(13.8±0.6)nm,and those of the tail-sheath-contracted non-functional molecules were(57.7±1.2)×(20.8±1.5)nm.Conclusions The novel R-type PTLB pro-duced by E.cloacae SHAMU191747 can efficiently kill MRSA,and has the potential to be developed into a novel antimicrobial drug with great prospects for clini-cal application.

Objective:To establish a predictive scoring model for bladder neck contracture(BNC)after laparoscopic enuclea-tion of the prostate with preservation of the urethra(Madigan surgery)and explore the preventive measures against this postoperative complication.Methods:We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022(45 with and 317 without postoperative BNC)in the training group and another 120 cases treated the same way in the verification group,collected the clinical data on the patients and evaluated the results of surgery.Using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression,we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors.Results:Compared with the baseline,the IPSS,quality of life(QOL)score and postvoid residual urine volume(PVR)were significantly decreased(P＜0.05)while the maximum urinary flow rate(Qmax)remarkably in-creased(P＜0.05)in the BPH patients at 3 months after surgery.Eight non-zero characteristic predictors were identified by LASSO regression analysis.Multivariate logistic regression analysis showed that short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature＜34℃,catheter blockage,urethral balloon injection volume＞40 ml and postoperative constipation were independent risk factors for postoperative BNC(P＜0.05).The best cut-off value was 2.36 points in both the training and the verification groups.The results of evaluation exhibited a high discriminability of the predictive scoring model.Conclusion:Laparo-scopic Madigan surgery is a safe and effective method for the treatment of BPH.Short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature＜34℃,catheter blockage,water injected into the urethral balloon＞40 ml and postop-erative constipation were independent risk factors for postoperative BNC.The predictive scoring model constructed in this study has a good discriminability and is simple and feasible,contributive to the prediction of postoperative BNC in BPH patients undergoing laparo-scopic Madigan surgery.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective To compare and analyze the application value of domestic Octoparms and imported Celect inferior vena cava filter(IVCF)in the interventional treatment of venous thromboembolism(VTE).Methods Forty patients with VTE were randomly divided into Octoparms group(experimental group)and Celect group(control group)according to the double-blinded method of the central random system.All the patients underwent filter placement,catheter-directed thrombolysis and filter retrieval.The primary end point was the success of filter placement and retrieval,and the secondary end point included indwelling complications such as the occurrence of pulmonary embolism(PE)and filter tilt and migration.Results Forty patients were enrolled in this study,22 patients and 18 patients were divided into the experimental group and the control group,respectively.Among them,11 cases were identified with right lower extremity deep vein thrombosis,29 cases with left lower extremity deep vein thrombosis,17 cases with PE,and 6 cases with inferior vena cava thrombosis.The success rate of IVCF placement was 100%in all participants.Immediately after filter place-ment,the angle of filter tilt was(3.8±2.3)° in the experimental group and(4.9±2.8)° in the control group(t=1.44,P=0.16).Filter retrieval was successful in 21 cases(21/22,95.5%)of the experimental group and 17 cases(17/18,95.5%)of the control group.There was no significant difference between the two groups(t=0.14,P=0.89).The mean indwelling time of filter was(8.0±2.1)days in the experimental group and(9.7±3.1)days in the control group(t=0.73,P=0.47).The angle of filter tilt was(5.3±3.4)° in the experimental group and(5.7±7.7)° in the control group(t=0.19,P=0.85).There was no significant difference for filter placement and retrieval between the two groups(t=0.48 and 2.00,P=0.06 and 0.64,respectively).There were no complications of filter migration,strut penetration or new PE in both groups.Conclusion The application value of domestic Octoparms and impor-ted Celect IVCF is similar in interventional treatment of VTE.

Objective To investigate the effect of vecuronium bromide on the malignant biological behavior of gastric cancer cells and its molecular mechanism.Methods Gastric cancer cells HGC-27 were divided into control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA-FGD5-AS1 group,pcDNA group,experimental-H+pcDNA group,experimental-H+pcDNA-FGD5-AS1 group.The control group was cultured conventionally;experimental-L,-M,-H groups were treated with 5,10 and 20μmol·mL-1 vecuronium bromide,respectively;si-FGD5-AS1 group and the si-NC group were transfected with lncRNA FGD5-AS1 interference expression vector and negative control plasmid,respectively;pcDNA-FGD5-AS1 group and pcDNA group were transfected with lncRNA FGD5-AS1 overexpression vector and negative control plasmid,respectively;lncRNA FGD5-AS1 overexpression vector and negative control plasmid were transfected into HGC-27 cells in the experimental-H+pcDNA-FGD5-AS1 group and experimental-H+pcDNA group,and then treated with 20 μmuol·mL-1 vecuronium bromide.Methyl thiazolyl tetrazolium(MTT),flow cytometry and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)were applied to dectect cell viability,apoptosis and lncRNA FGD5-AS1 expression.Results The cell activity of control group,experimental-L,-M,-H groups,si-NC group,si-FGD5-AS1 group,pcDNA group,PCDNA-FGD5-AS1 group,experimental-H+pcDNA group and experimental-H+PCDNA-FGD5-AS1 group were 1.31±0.07,0.58±0.03,1.31±0.06,0.51±0.03,1.29±0.08,1.68±0.15,0.59±0.03 and 1.16±0.06;the apoptosis rates were(6.49±0.44)％,(23.52±0.98)％,(6.42±0.44)％,(26.75±0.97)％,(6.72±0.38)％,(2.56±0.19)％,(23.56±1.04)％and(11.65±0.47)％;the expression levels of lncRNA FGD5-AS1 were 1.00±0.05,0.37±0.02,0.99±0.05,0.21±0.02,1.00±0.03,2.98±0.12,0.38±0.02 and 0.87±0.05,respectively.The above indexes were compared with the control group and experimental-H group,those in the si-FGD5-AS1 group were compared with the si-NC group,those in the pcDNA-FGD5-AS1 group were compared with the pcDNA group,and those in the experimental-H+pcDNA-FGD5-AS1 group were compared with the experimental-H+pcDNA group,the differences were statistically significant(all P＜0.05).Conclusion Vecuronium bromide may inhibit the proliferation of HGC-27 cells and promote cell apoptosis by down-regulating lncRNA FGD5-AS1.

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.