T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

20 years)was 8.60%(48/558) , which was more than that in the second decade of life ( 5.22% ). The incidence of painful group was 9.79%(14/143),which was more than that in foot trauma group 6.78%(40/630).The positive C sign was presented in 61.1%(33/54),posterior-type coalition in 38.9%(21/54),short talar neck sign in 61.1%(33/54)and talar beak sign in 22.2%(12/54). Conclusion The talocalcaneal coalition is a common development abnormality in our country. We must pay attention to the diagnosis of talocalcaneal coalition for painful foot adulthood.

Objective To study the incidence and radiologic findings of calcaneonavicular coalition.Methods CR films of foot andankle in 1361 cases were presented,which were evaluated for acute trauma or chronic pain.There were 588 cases of foot CR and 773 cases of ankle CR,age ranged from 10 years to 91 years(984 cases of 20~40 years).The prevalence of calcaneonavicular coalition was determined and the different significance of both male and female,acute trauma and chronic pain group were analysed.Results In 1361 cases,72 cases of calcaneonavicular coalition(5.3%) were demonstrated,8.7%(47/588)on foot CR films and 3.2%(25/773) on ankle CR films.Calcaneonavicular coalition was more dipicted on foot CR films than on ankle CR films(P0.05).Conclusion The foot CR films is more superexcellent than the ankle CR films on demonstrating calcaneonavicular coalition.

Objective To study the clinicoradiologic significance of C sign.Methods 773 cases of standard ankle CR radiographs were presented for diagnosis of acute trauma and ankle pain. There were 565 males and 208 females, ages ranged from 10 to 81. There were 630 cases of acute trauma and 143 cases of painful ankle. C sign incidence, C sign figuration, distance of the medial facet of talocalcaneal joint, and the figuration of sustentaculum tali were studied. The relationship between C sign and talocalcaneal coalition was analysed.Results The incidence of C sign was 54.6%(422/773). The female incidence was 61.1%(127/208) ,which was more than that of male(52.2%,295/565)(P

Objective To study the effects and mechanism of calycosin on oxidative stress andβ-cell apoptosis induced by streptozotocin (STZ). Methods RIN-m5F cells were divided into 5 groups:control group, STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. The control group did not receive any treatment, while streptozotocin was added to the final concentration of 10 mmol/L in STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. After the incubation with STZ for 6 h, calycosin was added to a final concentration of 10, 50 and 100 μmol/L in STZⅠgroup, STZⅡgroup and STZⅢgroup respectively. The cell viability and apoptosis was detected by CCK-8, LDH, caspase 3 and Tunel assay. The intracellular oxidative stress was measured using mitochondrial membrane potential, DCFH-DA, SOD activity and malondialdehyde levels assay. RIN-m5F cells were divided into control group, calycosinⅠgroup, calycosinⅡgroup and calycosinⅢgroup, which were treated with different concentrations (0,10, 50 and 100 μmol/L, respectively) of calycosin. The expression of NF-E2-related factor 2(Nrf2) in RIN- m5F cells was detected by Western blot. The translocation of Nrf2 was detected by immunofluorescence. In RIN-m5F cells were divided intoⅢgroup andⅣgroup,Ⅳgroup was pre-treated with protein kinase C(PKC) inhibitor. The effects of calycosin on Nrf2 translocation, oxidative stress and apoptosis were also observed. Results STZ could induce the accumulation of reactive oxygen species and apoptosis in RIN-m5F cells. Calycosin did not affect normal RIN-m5F cells, whereas it reduced the oxidative stress and apoptosis induced by STZ in a dose-dependent manner. The expression of Nrf2 in RIN-m5F cells was not affected by calycosin, whereas it promoted the translocation of Nrf2 into nucleus. The ability of calycosin promoting Nrf2 translocation was decreased after PKC inhibitor treatment, and PKC inhibitor could also significantly attenuate the anti-oxidant and anti-apoptotic ability of calycosin. Conclusions This study shows that calycosin may play an anti-oxidative and anti-apoptotic role by activating PKC to promote Nrf2 translocation, which is expected to be used as a new clinical drug for the prevention and treatment of diabetes mellitus.

Objective To explore the clinical and genetic characteristics of complex glycerol kinase deficiency (GKD). Methods The clinical data of 2 cases of complex GKD were analyzed and the related literatures were reviewed. Results Both cases were male onset in neonatal period, and had hypocorticalism (hyponatremia, hyperkalemia, dehydration), hypercreatine kinasemia, and pseudotriglyceridemia. Gene detection suggested that there was gene deletion in chromosome Xp21 region. In the follow-up, one case had good control of the disease and one died of infection. Conclusions Complex GKD is an X-linked recessive hereditary disease. It is rare and complicated, and is easily misdiagnosed. Early diagnosis and treatment are beneficial to improve the prognosis.

OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

Objective:To evaluate the effect and mechanism of bone regeneration in distraction osteogenesis zone after the repair of sciatic nerve in rats.Methods:Between January 2021 and August 2021, 60 healthy adult male Sprague-Dawley rats were divided randomly into 3 groups: Group A, B, and C. In groups B and C, right sciatic nerve transection and anastomosis were performed. Then after 8 and 12 weeks, the 3 groups were treated with extension external fixation (Ilizarov technique) of right femur osteotomy to make distraction osteogenesis model. Electrophysiological changes of peripheral nerves were monitored by electromyography (EMG) pre-and postoperatively in all the femoral lengthening rats. The formation of callus was examined by X-ray every week after operation. The rats were sacrificed on 2nd, 4th, 6th weeks after the bone transport operation. Four-point bending test and histological staining examination were carried out to determine the osteogenesis in the distracted area. SPSS 21.0 was used for statistical analysis. Data of measurement were expressed as (Mean±SD). A non-parametric test was used to assess the statistical difference between groups. Graphs were plotted by GraphPad Prism 8.0 and considered statistically significant when P<0.05. Results:The results of Sciatic nerve function index (SFI), Compound muscle action potential (CMAP) and Motor nerve conduction velocity (MNCV) in group A were better than the group B and group C in both of before and after the surgery. At the 2nd and 4th weeks of the consolidation stage, X-ray showed that bone formation in group B was superior to groups A and C; HE and Safranin O staining showed that local capillary and cartilage formation in group B was significantly more than in groups A and C; Immunohistochemical staining showed that the expression levels of Osteopontin(Opn) and Osteocalcin(Ocn) in the distraction area of group B were higher than that of groups A and C. At the 6th week of the consolidation stage, the four-point bending test showed that the bone quality of group B was better than groups A and C. The differences of the results between groups shown above had statistical significance ( P<0.05). Conclusion:Bone regeneration in the distraction area of the bone lengthening group with sciatic nerve injury was better than that of the bone lengthening group without a never injury. This might be in relation to the fact that a distractive osteogenesis caused the secondary injury to the repaired nerve. The electrophysiological results showed that periodic changes took place in the repaired sciatic nerve caused by the stretch of femoral lengthening, and the injurious changes of sciatic nerve would be gradually relieved in 6th week after surgery.

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
Saccharomyces cerevisiae/genetics* ; Sterols ; Phytosterols ; Biological Transport ; ATP-Binding Cassette Transporters/genetics*