The paper reports a case of 2,8-dihydroxyadenine (2,8-DHA) crystalline nephropathy caused by mutation of adenine phosphoribosyltransferase ( APRT) gene. The female patient was 60 years old, and sought medical advice due to "foaming urine increased for half a year". Renal biopsy result showed irregular yellowish brown 2,8-DHA crystals with refraction under polarized light. 2,8-DHA crystals were found by urine sediment detection, and homozygous deletion of c.521_523delTCT on exon 5 of APRT gene was found by genetic testing. Finally this patient was diagnosed as 2,8-DHA crystalline nephropathy. Renal function improved after treatment with allopurinol. The case report aims to improve the clinician's understanding of 2,8-DHA crystalline nephropathy. Early recognition, correct diagnosis, and early drug intervention may delay the progression of renal failure and improve the prognosis.

Objective:To evaluate the MRI manifestations of condylar bone regeneration after disc reduction and suture for anterior disc displacement without reduction (ADDWoR) patients and to analyze the relevant factors affecting bone regeneration.Methods:A total of 61 patients of 75 joints with ADDWoR who attended the Department of Maxillofacial Surgery of the Affiliated Hospital of Stomatology of Nanjing Medical University from April 2020 to December 2021 were enrolled in the study. The characteristics of MRI condylar bone regeneration were analyzed before and after surgery (follow-up for 6 months or more), and logistic regression analysis was performed on the influencing factors of bone regeneration.Results:The new bone formation of the condyle was found in 28 patients, with age of (20.2±4.9) years. However, there were 33 patients that had no condylar bone regeneration, with age of (41.9±17.5) years. A total of 35 joints in this study were found new bone formation. There were 16 joints (45.7%) had new bone formation on the posterior slope of the condyle, 10 joints (28.6%) around the condyle, 6 joints (17.1%) on the anterior slope of the condyle, and only 3 joints (8.6%) on the top of the condyle. Multivariate logistic regression analysis showed that age, preoperative disc length and degree of condylar bone resorption correlated with postoperative condylar bone regeneration( P<0.05). Patients younger than 30 years with non-shortened preoperative disc length and less condylar bone resorption have a higher probability of new bone formation. Conclusions:The condyle has bone regeneration capacity after correcting the abnormal relationship between disc and condyle, and young age, non-shortened preoperative disc length and less condylar bone resorption are conducive to postoperative condylar bone regeneration.

Objective:To identify the transmission relationship between HIV infection cases the non-marital non-commercial heterosexual contact in Zhejiang Province.Methods:When HIV positive was informed during January 2020 to January 2022, the staff conducted an epidemiological investigation to collect cases information on sociodemographic characteristics, mobility information, past HIV testing history, high-risk sexual behaviors, sexual partners, and etcetera. At the same time, 6-8 ml of blood from the new diagnosis of people infected with HIV before antiviral treatment was collected to separate the bleeding plasma. pol gene was amplified by nucleic acid extraction and PCR, sequenced by Sequencer 5.0 software, and Cytoscape 3.6.0 software was used to draw HIV molecular transmission network. Results:From January 2020 to January 2022, 88 HIV infected individuals were found in Pujiang County, of which 74 were transmitted through heterosexual transmission, of which 31 were infected through non-marital non-commercial heterosexual contact. Preliminary case studies have found that three female cases have engaged in unprotected non-marital non-commercial heterosexual contact with one male case. Among the 4 infected individuals, 2 of their spouses tested positive for HIV antibodies. Molecular transmission network monitoring was carried out on 65 newly diagnosed cases of heterosexual transmission with acquired sequences, forming 9 transmission clusters. The largest cluster contained 10 cases. A total of 11 HIV-infected individuals were involved in this HIV cluster epidemic. They were 3 males and 8 females, all over 50 years old and were farmers or rural housewives. They were traced to 7 sexual partners (6 negatives of HIV, 1 undetected). Among the 18 respondents' sexual social network relationships, there were 6 couples, 8 permanent partners, and 3 temporary partners. Among 11 HIV infected individuals, there were 9 cases of non-marital non-commercial heterosexual transmission and 2 cases of intramarital transmission. The epidemiological association between 7 non-married non-commercial heterosexual partners and case 2 (56-year-old male farmer), 3 cases confirmed by epidemiological investigation and molecular transmission cluster results, 3 cases confirmed by molecular transmission cluster and epidemiological investigation results, and 1 case confirmed by epidemiological investigation results.Conclusions:The transmission mode of this cluster epidemic was to spread HIV through heterosexual sex with a male case as the core, then cause the transmission within marriage and between fixed sexual partners. The combination of epidemiological investigation and molecular transmission network traceability survey supports the conclusion of this study.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Background: Tumor mutational burden (TMB) is a promising predictor, which can evaluate the efficacy of immune checkpoint inhibitors (ICIs) for tumor patients. MicroRNAs (miRNAs) act as the key regulators of anti - cancer immune response. However, the relationship between TMB and miRNAs expression profiles in gastric cancer is not elucidated. Aims: To construct and validate the TMB prediction model of gastric cancer by analyzing the sequencing data and clinical data in TCGA database. Methods: Gastric cancer patients in TCGA database were divided into TMB high group and TMB low group, and differentially expressed miRNAs were screened. Gastric cancer patients were randomly divided into training group and validation group. A miRNAs prediction model for predicting TMB level was developed by lasso regression analysis method in training group, and was validated in validation group. KEGG functional enrichment analysis was used to analyze the screening related miRNAs. The correlation between miRNAs and three ICIs was analyzed. Results: Fifty-four differentially expressed miRNAs were screened, and 20 of them were identified as TMB-related miRNAs. The sensitivity, specificity, AUC in the miRNAs prediction model were relatively high. Functional enrichment results revealed that TMB-related miRNAs were mainly involved in biological process associated with immune response and signaling pathways related with cancer. The miRNAs prediction model showed a median positive correlation with PD-L1 (r=0.36, P<0.01), a median negative correlation with PD-1 (r=-0.31, P<0.01) and no significant correlation with CTLA4 (r=0.14, P<0.01). Conclusions: This study presents a miRNAs prediction model which can stratify gastric cancer patients with different TMB levels.

Objective:To explore the impact of the expression of long noncoding RNA-nuclear-enriched abundant transcript 1 (NEAT1) on neurological function and neuronal apoptosis after traumatic brain injury (TBI) in mice and the possible mechanism.Methods:According to the random number table, 90 C57BL/6J mice were divided into sham group, blank control group, empty virus group 1, empty virus group 2, NEAT1 over-expression group and NEAT1 knockdown group, with 15 mice per group. The traumatic brain injury (TBI) was simulated by controlled cortical injury (CCI) model, and NEAT1 was regulated by intracerebroventricular injection with recombinant adenovirus. The neurological severity score (NSS) and Morris water maze test were used to evaluate the neurological function in blank control group, NEAT1 over-expression group and NEAT1 knockdown group within 1 week and 14-21 days after injury. The Western blot was used to observe the expressions of P53-induced protein with a death domain 1 (Pidd1), caspase-2, caspase-9 and caspase-3 in blank control group at 6 hour and 1, 3, 7 days after injury. The TUNEL method and immunofluorescence were used to observe the neurological apoptosis and expression of Pidd1 in blank control group, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury. The Western blot analysis was used to detect protein expressions of Pidd1, caspase-2, cytochrome c (Cyt c) and caspase-3 in sham group, blank control group, empty virus groups, NEAT1 over-expression group and NEAT1 knockdown group at 3 days after injury.Results:The NSS was significantly reduced in NEAT1 over-expression group [(3.5±0.7)points], and was significantly increased in NEAT1 knockdown group [(5.0±1.5)points]at day 1 after injury, when compared with blank control group [(4.9±1.0)points]( P<0.01). The Morris water maze test showed that the time to find platform was decreased in NEAT1 over-expression group[(10.9±2.8)seconds], and was prolonged in NEAT1 knockdown group [(30.7±6.2)seconds] at day 19 after injury ( P<0.05 or 0.01), when compared with blank control group [(20.1±5.6)seconds]. The Western blot analysis showed that the expressions of Pidd1, caspase-2, caspase-9 and caspase-3 had significant increase at day 3 after injury ( P<0.01). The TUNEL test showed that the apoptosis rate of neurons was significantly decreased in NEAT1 over-expression group [(18.0±2.7)%], and the apoptosis rate was significantly increased in NEAT1 knockdown group [(63.0±8.6)%] at day 3 after injury ( P<0.01). Immunofluorescence showed that the expression of Pidd1 protein in cytoplasm of the neurons was decreased in NEAT1 over-expression group [(22.7±2.2)%]( P<0.01), and was increased in NEAT1 knockdown group [(72.7±7.0)%]( P<0.01) at day 3 after injury, when compared with blank control group. The Western blot analysis showed that the expressions of Pidd1, capsase-2, Cyt c and caspase-3 were significantly reduced in NEAT1 over-expression group (0.5±0.0, 0.3±0.0, 0.5±0.0, 0.4±0.0) at day 3 after injury, when compared with blank control group. However, the results were opposite in NEAT1 knockdown group. Conclusion:After TBI, the NEAT1 can reduce the activation of caspase-3 through the Pidd1-caspase-2-Cyt c pathway after TBI, regulate neuronal apoptosis, and ultimately play a protective role in neurological function.

Objective:To evaluate early corneal biomechanical change, safety and effectiveness after small-incision lenticule extraction combined with ultraviolet A corneal collagen cross-linking (SMILE-CXL) for myopic eyes and compare with SMILE.Methods:A non-randomized controlled clinical study was performed.Forty-four myopic eyes of 25 patients were included in Hankou Aier Eye Hospital from December 2017 to July 2018.SMILE-CXL or SMILE was carried out for 22 eyes of 12 patients or 22 eyes of 13 patients, respectively, based on the normal posterior surface manifestation of Belin by Pentacam tomography or not.The posterior surface manifestation of Belin was normal in the SMILE group, and the posterior surface of Belin was yellow or red with Corvis biomechanical index and tomographic biomechanical index<0.3 (except keratoconus) in the SMILE-CXL group.The refractive diopter of the eyes was detected before and 6 months after surgery, including spherical diopter, cylindrical diopter and spherical equivalent (SE) with a comprehensive refractometer.The corneal biomechanical parameters of the eyes were detected before and 6 months after surgery with a Scheimpflug-based dynamic tonometry (Corvis ST). The safety index, a ratio of postoperative mean best corrected visual acuity (BCVA) to preoperative mean BCVA, and efficacy index, a ratio of postoperative uncorrected visual acuity (UCVA) to preoperative BCVA, were compared between SMILE-CXL group and SMILE group.BCVA and UCVA were examined using standard chart and converted to logarithm of the minimal angle of resolution (LogMAR) units.This protocol complied with the Declaration of Helsinki and was approved by an Ethics Committee of Hankou Aier Eye Hospital (No.WHS2017052701). Written informed consent was obtained from each patient prior to entering into the cohort.Results:The postoperative UCVA of the eyes in both groups was more than 1.0.There were no significant differences in safety index, efficacy index and SE change between the SMILE-CXL group and SMILE group (all at P≥0.05). At 6 months after surgery, the values of second applanation time (A2T), time from the start until the highest concavity (HC-Time) and DA ratio 2 mm were significantly increased in comparison with before operation in both SMILE-CXL group and SMILE group (all at P<0.05). The changes of A2T, HC-Time and DA ratio 2 mm in the SMILE-CXL group were significantly lowered than those in the SMILE group at the sixth month after surgery ( P=0.001, 0.001, 0.036). The deformation amplitude, maximum corneal velocity during the first applanation (Vin), distance between both non-deformed peaks and integrated radius during the maximum depression were significantly increased, and the central curvature radius at highest concavity, cord length of first applanation, cord length of second applanation, Ambrósio's relational thickness horizontal, stiffness parameter applanation 1 and biomechanical intraocular pressure during the maximum depression were significantly lower at the sixth month after surgery than those before surgery (all at P<0.05). There were no significant differences in the parameters mentioned above between the two groups (all at P<0.05). Conclusions:Compared with SMILE alone, SMILE-CXL shows a comparable safety and efficacy, and better corneal biomechanical properties.

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.

Panax ginseng is a traditional Chinese medicine with significant pharmaceutical effects and wide application. Through orientational modification and transformation of ginsenoside glycosyl, rare ginsenosides with high antitumor activities can be generated. Traditional chemical methods cannot be applied in clinic. because of extremely complex preparation technologies and very high cost Transformations using microorganisms and their enzymatic systems provide the most feasible methods for solving the main problems. At present, the key problems in enzymatic synthesis of ginsenosides include low specific enzyme activities, identity of enzymes involved in the enzymatic synthesis, and their catalytic mechanisms, as well as nonsystematic studies on structural bioinformatics; specificity of enzymatic hydrolysis for saponin glycosyl has been rarely studied. Many reviews have been reported on glycosidase molecular recognition, immobilization, and biotransformation in ionic liquids (ILs), whereas ginsenoside transformation and application have not been systematically studied. To evaluate theoretical and applied studies on ginsenoside-oriented biotransformation, by reviewing the latest developments in related fields and evaluating the widely applied biocatalytic strategy, this review aims to evaluate the ginsenoside-oriented transformation method with improved product specificity, increased biocatalytic efficiency, and industrial application prospect based on the designed transformations of enzyme and solvent engineering of ILs. Therefore, useful theoretical and experimental evidence can be obtained for the development of ginsenoside anticancer drugs, large-scale preparation, and clinical applications in cancer therapy.
Biocatalysis ; Ginsenosides ; Glycoside Hydrolases ; Panax ; Saponins

Long non-coding RNA regulates gene expression at multiple levels (epigenetics,transcriptional level,post-transcriptional level) and plays an important role in the development and progression of individual development and tumors.With the deep research,it is found that LncRNA CRNDE is an important cancer-related long non-coding RNA,and it is necessary to understand the specific role of LncRNA CRNDE in regulating tumor cell life activities.In recent years,the role of LncRNA CRNDE in tumorigenesis and development has been increasing.It has been found that LncRNA CRNDE is up-regulated in various tumors and is closely related to tumor proliferation,invasion,metastasis and patients' prognosis,becoming a new hot spot in cancer research.The author combines the latest literatures at home and abroad to review the role and mechanism of LncRNA CRNDE in the development of digestive system tumors,hoping to prevent and treat tumors in the future.