The therapeutic effect of sustained intravitreal injectable voriconazole microspheres (VCZ-MS) on an experimental endophthalmitis of Aspergillus fumigatus was investigated. VCZ-MS was prepared successfully and its physico-chemical property was also evaluated. Right eyes of albino rabbits were infected with an intravitreal injection of 1 000 CFU x mL(-1) of susceptible Aspergillus fumigatus. All fungal endophthalmitis models were randomly divided into five groups 48 hours later: Group A is control group with no treatment; in group B, vitrectomy was performed combined with intravitreal 3 times injections of 100 microg x 0.1 mL(-1) voriconazole every other day. In group C, D and E, vitrectomy was performed combined with intravitreal injection of 0.5 mg, 1.0 mg and 1.5 mg VCZ-MS respectively. The treatment effect was assessed by slit lamp and indirect ophthalmoscope funduscopy examination, using clinical grading system of inflammation in the anterior chamber and the vitreous opacity. The optical microscopy revealed that microspheres obtained from the experiment design were opaque, discrete and spherical particles with smooth surfaces. The drug content and encapsulation efficiency of microspheres were 29.94% and 73.5%, respectively. Endophthalmitis occurred in all eyes of group A, and rapidly developed to panophthalmitis. The inflammation grade of group B, C, D or E was lower than that of group A (P < 0.05). The grade of vitreous opacity in group C, D, E is lower than group B (P < 0.05). Two eyes in group C developed to panophthalmitis. But in group D and E, all eyes whose inflammation was controlled had no recurrence with vitreous clear. Histopathological examination showed normal structures in the cured eyes, while most uncured eyes were atrophic and with eyeball destroyed. So, it can be safely concluded that the curative effect of intravitreal VCZ-MS is significantly better than that of routine intraocular injection of voriconazole. The optimal dose is the one containing 1.0 mg voriconazole.

Objective To evaluate the effects of TIMP-1 and Ang-1 gene-modified BMSCs transplantation on the left ventricular function of rats with myocardial infarction.Methods The rat BMSCs were.transfected with eukaryotic expression plasmid encoding TIMP-1 or/and Ang-1 gene by liposome.Acute myocardial infarction was made in male rats by ligation of the left anterior descending (LAD) coronary artery.BMSCs carrying TIMP-1 or/and Ang-1 gene were injected into the ischemic myocardium after LAD ligatior.Four weeks after the administration,cardiac function was assessed by echocardiography and the hearts were harvested and sectioned for immunohistochemistry to examine the apoptosis,the collagen content and angiogenesis density.Results TIMP-1 and Ang-1 genemodified BMSCs transplantation significantly improved the cardiac function,myocardial apoptosis was alleviated,collagen content decreased and the angiogenesis density in border-zone was increased significantly (P＜0.05).Conclusions The results suggest that the combination of TIMP-1 and Ang-1-gene modified BMSCs transplantation can improve the cardiac function of rats with myocardial infarction.The increase of the blood supply,the alleviation of myocardial apoptosis and ventricle remolding after myocardial infarction possibly play important roles in the mechanism.

Objective To investigate the effect of acupunctures variable with stages on lumbar intervertebral dise protrusion (LIDP). Methods 98 LIDP patients in our hospital from October, 2014 to July, 2015 were randomly divided into control group (n=49) and observa-tion group (n=49) according to the sequence of first diagnosis time. The control group received routine acupuncture, and the observation group acupunctured at Ouch point and Huantiao point (GB30) with different acupuncture according to manifestations and courses. Modified Yang acupuncture was adopted in acute phase, triple acupuncture was used in remittent phase, and lateral needling was used in the recovery phase. They were both treated once a day, 7 days as a course for 3 courses with 2 days of interval. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and clinical effects were assessed before and 1, 2, 3 courses after treatment. Results Both VAS and ODI scores im-proved after treatment (F>7.12, P<0.05), especially in the observation group (t>4.43, P<0.05). The efficiency was higher in the observation group than in the control group (χ2=5.594, P<0.05). Conclusion Compared with normal acupuncture, the acupunctures variable with stages is more effective on LIDP than routine.

Research based learning (RBL) is a brand new teaching mode implicated by Shanghai Jiaotong University School of Medicine specifically designed for clinical undergraduates.The nature of RBL is about exploring unknown knowledge and designing and executing comprehensive experiments.RBL aims at creating an open,active student participation,and close student-mentor interaction teaching mode.IBL includes literature study,research aim selection,experiment design and implementation,statistical analysis,results and conclusions,final report writing and defense of the report.Our experience indicates that RBL can substantially improve students' scientific logic and critical thinking and experimental skills,and develop the spirit of a team-player.This scientific training enables students to receive more comprehensive scientific training,facilitate their subsequent clinical research and practice,and assist them to participate in more international scientific exchanges.We propose that the RBL mode should be adopted for clinical student education in other universities.

Objective To analyze the clinical data and TUBB4A mutation of hypomyelination with atrophy of the basal ganglia and cerebellum (HABC)in a family,thus to provide accurate genetic counseling and prenatal diagno-sis for this family with HABC,and also to provide clinical experience for the diagnosis of HABC in China.Methods The clinical data of the proband and her family members were collected at the Department of Pediatrics,Peking Univer-sity First Hospital,December 201 4,including medical history,physical signs,and brain MRI,biochemical tests and metabolic disease screening.The associated gene of hereditary leukoencephalopathy was screened for the proband and her family members were screened by targeting -high -throughput sequencing technology,and then the genetic varia-tions were verified by Sanger sequencing.With those detection methods,the gene mutation was confirmed,and then ge-netic features were analyzed.Results Clinical features were as follows:nystagmus as the first symptom,and motor and mental retardation,dystonia and ataxia followed.Brain MRI indicated hypomyelination of white matter and atrophy of the basal ganglia and cerebellum.The clinical diagnosis of HABC was established based on the clinical features and brain MRI features above.Genetics features showed that one novel TUBB4A c.974G >T heterozygous missense muta-tion was found from the proband,which caused an amino acid change from the Trp into Leu (p.Trp325Leu).Both of her parents with normal phenotype were of wild -type in this site.Conclusions The proband from this family was diagnosed clinically based on her clinical data.One novel TUBB4Ac.974G > T (p.Trp325Leu)was founded in this study.Therefore,the spectrum of TUBB4A mutation will be expanded.In addition,this study elucidated clinical and genetic characteristics in this family with HABC,which may lay a solid foundation for the accurate genetic counseling and prenatal diagnosis.This study reported the first case of HABC caused by TUBB4A mutation in China.

We investigated the situation of leptosperosis infection among patients with fever in Hainan Province in China.Blood samples of patient from Hainan Province in the year of 2015 were detected for Leptospira by microscope agglutination test (MAT),enzyme-linked immunity test (ELISA) and polymerase chain reaction (PCR),respectively.Results showed that 179 blood samples of patients with fever were found,and microscope agglutination test detected 40 positive samples,with a infection rate of 22.35％.The infection rate was 21.65％(21/97) for male and 23.17％(19/82) for female.Seven groups of bac teria were found including Leptospira serogroup icterohemorrhagie,ballom group,autumralis group,pomona group,grippotyphosa group,Sejroe group and Batavia group.Thirty-eight samples were tested positive by ELISA,with a positive rate of 21.23 ％,in which six samples were IgM positive (detection rate =3.35 ％) and 32 samples were IgG positive (detection rate=17.88 ％).Serological detected with MAT and ELISA methods results were consistent and that were tested negative by PCR.Results of our study supported the presence of Leptospira infection infection among the patients with fever of unknown origin (FUO) in Hainan Province.The main types are Leptospira serogroup icterohemorrhagie.

Objective To analyze differentially expressed genes and potential microRNA(miR-NAs)with diagnostic and therapeutic potential in ulcerative colitis(UC)based on bioinformatics.Methods The chip raw data in GEO database was screened by weighted gene coexpression network analysis.UC related differentially expressed genes were obtained for enrichment analysis.Potential miRNAs associated with differentially expressed genes were predicted based on key genes,and gene-miRNA regulatory networks were constructed.Results A total of 277 differentially expressed genes were screened,of which 200 genes were up-regulated and 77 genes were down-regulated.Gene set en-richment analysis(GSEA)showed that the main enrichment pathways were neuroactive ligand-receptor interaction,leishmania infection,prion disease and electrocardiogram receptor interaction.The results of gene ontology(GO)analysis showed that it was mainly involved in chemokine activity,heparin binding as well as chemokine receptor binding and other items.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that the main enrichment pathways were cytokine receptor interaction pathway,phosphatidylinositol-3 kinase/protein kinase B(PI3K-AKT)signaling pathway,chemokine signaling pathway as well as nuclear transcription factor kappa B(NF-κB)signaling pathway and other pathway.A total of 10 hub genes were screened:C-X-C chemokine ligand 8(CXCL8),Toll-like receptor 2(TLR2),intercellular adhesion molecule-1(ICAM-1),selectin L(SELL),C-X-C chemokine receptor type 4(CXCR4),cytotoxic T lymphocyte associated antigen 4(CTLA4),clus-ter of differentiation 69(CD69),and Biglycan(BGN),C-X-C chemokine ligand 13(CXCL13),tissue inhibitor of metalloproteinases 1(TIMP1).A total of 12 potentially key miRNAs were identi-fied,they were respectively hsa-mir-335-5p,hsa-mir-146a-5p,hsa-mir-92a-3p,hsa-mir-155-5p,hsa-mir-26b-5p,hsa-mir-4426,hsa-mir-4462b,hsa-mir-4647,hsa-mir-32-5p,hsa-mir-92b-3p,hsa-mir-98-5p and hsa-mir-93-5p,respectively.Conclusion In this study,a total of 277 differen-tially expressed genes are screened for possible involvement in the development of UC,and 10 hub genes and 12 miRNAs are identified as possible biomarkers for UC.

Objective To analyze differentially expressed genes and potential microRNA(miR-NAs)with diagnostic and therapeutic potential in ulcerative colitis(UC)based on bioinformatics.Methods The chip raw data in GEO database was screened by weighted gene coexpression network analysis.UC related differentially expressed genes were obtained for enrichment analysis.Potential miRNAs associated with differentially expressed genes were predicted based on key genes,and gene-miRNA regulatory networks were constructed.Results A total of 277 differentially expressed genes were screened,of which 200 genes were up-regulated and 77 genes were down-regulated.Gene set en-richment analysis(GSEA)showed that the main enrichment pathways were neuroactive ligand-receptor interaction,leishmania infection,prion disease and electrocardiogram receptor interaction.The results of gene ontology(GO)analysis showed that it was mainly involved in chemokine activity,heparin binding as well as chemokine receptor binding and other items.The Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis showed that the main enrichment pathways were cytokine receptor interaction pathway,phosphatidylinositol-3 kinase/protein kinase B(PI3K-AKT)signaling pathway,chemokine signaling pathway as well as nuclear transcription factor kappa B(NF-κB)signaling pathway and other pathway.A total of 10 hub genes were screened:C-X-C chemokine ligand 8(CXCL8),Toll-like receptor 2(TLR2),intercellular adhesion molecule-1(ICAM-1),selectin L(SELL),C-X-C chemokine receptor type 4(CXCR4),cytotoxic T lymphocyte associated antigen 4(CTLA4),clus-ter of differentiation 69(CD69),and Biglycan(BGN),C-X-C chemokine ligand 13(CXCL13),tissue inhibitor of metalloproteinases 1(TIMP1).A total of 12 potentially key miRNAs were identi-fied,they were respectively hsa-mir-335-5p,hsa-mir-146a-5p,hsa-mir-92a-3p,hsa-mir-155-5p,hsa-mir-26b-5p,hsa-mir-4426,hsa-mir-4462b,hsa-mir-4647,hsa-mir-32-5p,hsa-mir-92b-3p,hsa-mir-98-5p and hsa-mir-93-5p,respectively.Conclusion In this study,a total of 277 differen-tially expressed genes are screened for possible involvement in the development of UC,and 10 hub genes and 12 miRNAs are identified as possible biomarkers for UC.

Objective To construct a diagnostic model for the phlegm-dampness obstruction syndrome in patients with coronary heart disease stable angina pectoris(CSAP);To provide a reference for clinical syndrome differentiation.Methods Totally 305 patients'clinical data were collected from the Department of Cardiology,Dongying Hospital Affiliated to Shandong University of Traditional Chinese Medicine,from May 2022 to January 2024.The least absolute shrinkage and selection operator(LASSO)was used to select features,and multiple models were constructed and compared using machine learning(ML)algorithms.The optimal ML model was selected for training,validation,and testing.Finally,the operational logic of the optimal model was explained using Shapley Additive Explanations(SHAP),and two typical examples were provided to help users understand the model's operational logic.Results LASSO regression identified chest pain,body mass index(BMI),limb heaviness,drinking history,age,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)as features included in the model.After comparing multiple models,the Gaussian Naive Bayes(GNB)model demonstrated the best performance.The final constructed GNB model achieved an average AUC of 0.938(95%CI:0.903-0.972)in the training set,an average AUC of 0.927(95%CI:0.851-0.992)in the validation set,and an AUC of 0.856(95%CI:0.751-0.961)in the test set.The learning curve showed that the error between the training and validation sets in the model converged as the number of training samples increased.The calibration curve showed that the model had good consistency in predicting the probability of observed phlegm-dampness obstruction syndrome patients.The clinical decision curve(DCA)showed that the model could provide clinical benefits for patients at a decision threshold below 0.7.The features ranked by SHAP importance in order were chest pain,BMI,LDL-C,TG,limb heaviness,TC,drinking history and age.Conclusion The diagnostic model for CSAP phlegm-dampness obstruction syndrome constructed in this study can assist physicians in the syndrome differentiation of patients,thereby enabling the formulation of integrated clinical treatment plans combining traditional Chinese and Western medicine,and aiding patients in achieving better clinical therapeutic outcomes.

Objective To investigate the clinical effects of laparoscopic pancreaticoduodenectomy (LPD) for distal cholangiocarcinoma.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 37 patients who underwent LPD for distal cholangiocarcinoma in the Hunan Provincial People's Hospital between January 2013 and November 2016 were collected.LPD for distal cholangiocarcinoma was performed using the "en-block" procedure.According to the principle of "one axis,two planes and four zones",anatomy used posterior approach,anterior approach and medial approach,lymph node dissection was performed from carotid sheath outside,and en bloc specimens were resected.Observation indicators:(1) surgical and postoperative recovery situations;(2) postoperative pathological examination;(3) follow-up and survival situations.Follow-up using outpatient examination was performed to detect the patients' recurrence-free survival up to November 2017.Measurement data with normal distribution were represented as (x)±s.The survival curve and rate were drawn and calculated by the Kaplan-Meier method.Results (1) Surgical and postoperative recovery situations:all the 37 patients underwent successful LPD,without conversion to open surgery and perioperative death.The operation time,volume of blood loss and case with intraoperative blood transfusion were (326 ± 55) minutes,(176± 39)mL and 1,respectively.The time to initial exsufflation and time for diet intake were respectively (4.5± 1.6)days and (5.3±2.7)days.Of 37 patients,14 had postoperative complications,including 8 with pancreatic fistula (6 with biochemical fistula and 2 with grade B pancreatic fistula),1 with biliary fistula,3 with postoperative bleeding (2 with intra-abdominal bleeding and 1 with gastrointestinal anastomosis bleeding),2 with delayed gastric emptying (grage A),2 with intra-abdominal infection and 2 with pulmonary infection;the same patients can merge multiple complications.Three patients were in Clavien-Dindo classification ≥ Ⅲ.One patient received reoperation and other patients were improved by symptomatic treatment.Duration of hospital stay of 37 patients was 13.5 days (range,8.0-33.0 days).Eight patients underwent adjuvant chemotherapy of 4-6 cycles by taking orally tegafur or gemcitabine with cisplatin.(2) Postoperative pathological examination:tumor diameter and pancreatic duct diameter of 37 patients were (2.1±1.1)cm and (2.5±1.2) mm,respectively.Of 37 patients,9,13 and 15 were respectively detected in high-differentiated,moderate-differentiated and lowdifferentiated adenocarcinoma.Surgical margins:35 patients received R0 resection and 2 received R1 resection.Number of lymph node dissected,cases with lymph node metastasis and number of positive lymph nodes were respectively 18.5±4.9,16 and 1.7± 1.4.Analysis of lymph node metastasis location showed that the positive rates in 8a,12,13,14 and 17 groups lymph nodes were respectively 5.4％ (2/37),18.9％ (7/37),21.6％ (8/37),8.1％ (3/37) and 10.8％ (4/37);Perineural invasion (PNI),lymphovascular invasion (LVI),pancreatic invasion and duodenal invasion were identified in 14,9,16 and 6 patients,respectively.TNM stage:stage 0,Ⅰ A,Ⅰ B,ⅡA and Ⅱ B were respectively detected in 1,3,5,12 and 16 patients.(3) Follow-up situation:of 37 patients,36 were followed up for 6-45 months,with a median time of 26 months.The median recurrence-free survival time,1-and 3-year recurrence-free survival rates were respectively 28 months,80.6％ and 42.2％.Conclusion LPD is safe and effective for distal cholangiocarcinoma,and "en-block" resection not only helps to optimize the process of LPD for distal cholangiocarcinoma,but also has a significant effect on R0 resection and lymph node dissection.