Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective:To establish a model of patellar dislocation by femoral osteotomy or surgical release of medial retinaculum in immature rabbits, and observe morphological and trabecular microarchitectural changes in the trochlea.Methods:Forty rabbits at 3 months of age were included. All right knees underwent surgery, 20 knees were treated with femoral osteotomy and internal rotation of distal femur to increase femoral anteversion angle (Osteotomy group, OS group), and another 20 knees were treated with surgical release of medial retinaculum and overlap suture of lateral retinaculum (Soft tissue group, ST group). All left knees were acting as internal controls. Micro-CT scans for distal femur were acquired after 4 months post surgery. the height of Medial, central, and lateral trochlear, sulcus angle, and lateral and medial trochlear slope were measured to describe the trochlear morphology, and bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.Sp), and bone mineral density (BMD) were calculated to evaluate the microarchitectural structure. All parameters were compared between groups.Results:In OS group, one rabbit sustained a hip dislocation without patellar dislocation. Three knees developed complete patellar dislocation in daily flexion position, and the remaining 16 patellae were dislocated when the knee was placed in the maximal extension position. In ST group, 15 knees were complete patellar dislocation in daily flexion position, and 5 knees were without dislocation. A local boss was formed proximal to the entrance of the groove and the articular cartilage was smooth, and no obvious osteoarthritis was observed in OS group. In ST group no boss was formed, while obvious cartilage degeneration and defect was seen. Compared to the control group, the central trochlear height and sulcus angle were greater in both groups, but without significant difference between the two groups. The Tb.Th was increased in both medial and lateral condyle, and Tb.N was decreased in medial condyle compared with its control knees in OS group. The BV/TV, Tb.Th, Tb.N and BMD were decreased and Tb.Sp was increased in both medial and lateral condyle compared with its control knees in ST group. Compared to the OS group, the BV/TV, Tb.Th, Tb.N and BMD were smaller and Tb.Sp was greater in both medial and lateral condyle in ST group, with significant differences.Conclusion:The model of patellar dislocation could be successfully achieved by femoral rotational osteotomy to increase femoral anteversion or surgical release of medial retinaculum and overlap suture of lateral retinaculum, and subsequent morphological and trabecular microarchitectural changes in the trochlea are different. Different bony and soft tissue factors should be addressed for different patients with patellar dislocation in clinical practice.

Objective: The outbreak of novel coronavirus raised many problems in the auxiliary information system of epidemic prevention and control, which including the need to prevent key data from being illegal modification, traceability, lack of decision support systems at different levels, barriers to cross regional cooperation and low automation of case diagnosis. Methods: In this paper, artificial intelligence, security computing supporting privacy protection, block chain and other emerging technologies are introduced into the epidemic prevention and control auxiliary information system. Results: This paper discusses how to utilize modern cryptography and block chain technology to establish a traceability system that could assure the security of epidemic information; design a distributed decision support system; solve the privacy-preserving problems of Federated Learning based on SGX technology, and present a group architecture to alleviate the performance cost of SGX. Conclusions The schemes above can help to achieve the security and traceability of epidemic information, also improve the automation and decision-making efficiency of the auxiliary information system for epidemic prevention and control.

There has been a significant increase in the number of patients with alcoholic pancreatitis in recent years, and the pathogenesis of alcoholic pancreatitis is associated with various factors including genetic factors, smoking, and gut microbiota. Alcoholic pancreatitis is different from other types of pancreatitis in epidemiological features and clinical manifestations. This article reviews the research advances in the epidemiological features, pathogenesis, clinical manifestations, treatment, and prognosis of alcoholic pancreatitis.

Objective To study the association between the expression of periostin and the occurrence and progression of knee osteoarthritis (OA) in synovial fluid.Methods The expression level of periostin in the synovial fluid of healthy people and patients with different stages of OA was tested.Furthermore,60 surgical-induced OA rat model were divided into two groups,the sham operation group had only implemented slit suture,and the OA model group had one side anterior cruciate ligament transected.The expression of periostin in intra-articular injection samples were analyzed at 1,2,4,8,12 week.Fluorescence molecular tomography (FMT) were performed after surgery at 4,8,12 week on the surgery knee.Gross morphologic lesions on the tibial plateau in rats were visualized by India ink staining,toluidine blue staining,cartilage permeation test.The synovium were visualized by HE staining and periostin were detected by immunohistoc hemistry.The measurement data were compared by one factor analysis of variance test.Results The expression of periostin in cartilage was lower in late-stage OA than the one from normal and early-stage OA (F=13.95,P＜0.01).The FMT showed that there was no obvious change in the extent of chronic inflammation in the sham operation group,and the chronic inflammatory degree of the OA model group gradually increased as time went on.Toluidine blue staining and cartilage permeation test showed that the cartilage degeneration in rat model of OA became more and more serious with time.There was no stastically significant difference of the periostin in control groutp at different time stage (F=0.67,P=0.53).The periostin in the intra-articular increased at first and then decreased with the development of OA (F=11.0,P＜0.05).HE staining of synovial tissue showed that the degree of synovial hyperplasia was consistent with the degree of degeneration of joints.With the extension of time,the expression of periostin in synovial tissue increased gradually.Conclusion The expression of periostin in human synovial fluid is low in normal knee joint,increases in early and middle stages,and decreases in late stage.The rat model indicates that the expression of periostin increases first and then decreases with the development of OA,but the expression in synovium increases gradually with the development of OA.The increased expression of periostin in synovial fluid may serve as an early diagnostic marker for OA and downregulation of the periostin may be a start marker for the late OA.

Objective To investigate the VATS lobectomy and lymph node dissection impact on lung function and the survival rate in patients with different pathological types of lung cancer.Methods One hundred and twenty five cases of lung cancer patients underwent laparoscopic lobectomy and mediastinal lymph node dis-section as research subjects from June 2009 to September 2011 in our hospital.The patients were divided into pa-thology group( AG) ,squamous cell carcinoma( SG) and large cell carcinoma group( LG) according to the type of cancer.The clinical effects were observed before and after surgery,lung function and survival rate.Results LG Group in operative time,blood loss and postoperative chest tube drainage were higher than SG group AG group( P<0.05);AG group blood loss,postoperative chest tube drainage,blood transfusion after surgery and postoperative recovery times were higher than the SG group(P<0.05);LG group was higher than AG group(P<0.05)in terms of FVC%;LG Group,AG group in FVC%,FEF50%,FEF75%respects SG group were significantly differ-ent(P<0.05);18-month survival rate of patients in each group after the first follow up results of less than 12 months(P<0.05).SG group at 12,18-month survival rates were higher than AG group and LG group(P<0.05).Conclusion Laparoscopic lobectomy combined treatment of pathological lymph node dissection in pa-tients with different types of lung cancer,large cell carcinoma surgery operative time,blood loss and postoperative chest tube drainaged are higher than adenocarcinoma,squamous cell carcinoma;squamous cell survival and physi-cal evaluation of patients are higher than the other groups.

Objective To investigate the most appropriate surgical methods,different surgical modes of osmidrosis and their clinical effi-cacy were observed. Methods Clinical data was collected from 200 cases of axillary osmidrosis from January 2011 to July 2013. These cases were divided into four groups of the traditional group,minimally invasive group,RF pen-frequency electric cautery group and improved curet-tage group. Results The traditional group(80 cases) has an average healing period of 18. 7 days for operative incision including 78 cured cases(97. 5%)and 2 significant improved cases(2. 5%). The minimally invasive group(60 cases)has an average healing time of 8. 6 days, among which there are 3 cured cases(5%),8 significant improved cases(13. 3%),16 improved cases(26. 7%),4 cases(6. 7%)with weak curative effect and 29 failed cases(48. 3%). In the RF pen-frequency electric cautery group(30 cases),there are 5 significant improved ca-ses(16.7%),8improvedcases(26.7%)and17failedcases(56.6%).Theimprovedcurettagegroup(30cases)withanaverageincision healingtimeof9.8dayscontains28curedcases(93.3%)and2significantimprovedcases(6.7%). Conclusion Thetraditionalgroup shows the best curative effect,nevertheless the incision needs a considerably amount of time to recover. The patients under the treatment of minimally invasive surgery or RF pen-frequency electric cautery can recover in short time but recrudescence always occur. The improved cu-rettage method,which is effective and safe,combines the advantages of traditional surgery and minimally invasive surgery. However,large scar left from this method still remains as its major disadvantage but the overall curative effect is satisfactory. The improved curettage is proved to be the most appropriate method for axillary osmidrosis.

Objective To analys hyperinsulinemia in Bartter syndrome. Methods Twenty-three cases of Bartter syndrome [age (27 ±9) years;fasting serum potassium(2. 8 ±0. 5)mmol/L], 20 patients of aldosterone-producing adenoma [APA, age (45 ± 11 ) years, fasting serum potassium ( 3.0 ± 0. 4 ) mmol/L], 20 patients of idiopathic hyperaldosteronism [IHA, age (51 ± 11 ) years, fasting serum potassium (3.4 ±0. 2)mmol/L] were diagnosed in Peking Union Medical College Hospital from September 2003 to May 2008. All patients underwent 3-hours oral glucose tolerance test(3hOGTT), postural stimulation test and calculated HOMA-insulin resistance ( HOMA-IR ) and HOMA-insulin sensitivity ( HOMA-IS ) by Homeostasis model.Results The insulin area under curve-(229.0±162.4)mIU·L-1·h] was singnificantly higher than APA group [(227.7±158.6)mIU·-1·h].But HOMA-IR in Bartter group were similar to APA group( 1.96 ± 1.14 vs 1.41 ± 0. 91 ), and HOMA-IR in APA group was lower than IHA group ( 1.96 ± 1.14 vs 2.40 ± 1.60, P ＜ 0. 05 ). There was no deference in HOMA-IS among three groups,but APA group had lower level. In all three groups, the peak of insulin secretion was delayed. Conclusion Bartter syndrome patients commonly present with hyperinsulinemia.

Objective To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. Methods ( 1 ) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. Results (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother:c1193 T→C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A→ G (N312S) and c1065 T→C(same sense mutation). Conclusions (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.

Background and purpose:Connective tissue growth factor(CTGF) is a member of CCN family,it has been reported that CTGF involve in many biological processes and various pathological conditions.In our study,the correlation of CTGF expression and biological effects on breast cancer cell lines were investigated.Methods:The eukaryotic expression vectors containing CTGF open reading frame(ORF) pcDNA3.0/CTGF were constructed and transfected into breast cancer cell lines.The relationship between CTGF expression and breast cancer cell growth ability and proliferation,cell cycle distribution,apoptosis,cell motility and invasive capacity in vitro were observed.Results:Upregulation of CTGF expression in MCF-7 cell line could inhibit its growth ability and proliferation,increased the proportion of G0G1 phase cells,enhanced apoptosis and inhibited its invasive ability in vitro.Downregulation of CTGF expression in MDA-MB-231 cell line increased its growth ability and proliferation,decreased apoptosis and promoted its invasive ability in vitro.There were no differences of cell motility among different groups in MCF-7 and MDA-MB-231 cell lines.Conclusions:CTGF can inhibit breast cancer cell growth by increasing cell apoptosis and/or the proportion of cells in G0G1 phase.CTGF can also inhibit breast cancer cell invasive ability.