Objective To investigate the clinical effect and safety of bronchial arterial chemoembolization(BACE)combined with micro wave ablation(MW A)and immunotherapy in treating patients with advanced lung squamous cell carcinoma.Methods The clinical data of 68 patients with advanced lung squamous cell carcinoma,who were admitted to the North Jiangsu People's Hospital of China from June 2020 to June 2022 to receive treatment,were retrospectively analyzed.According to the therapeutic method,the patients were divided into control group(n=30,receiving BACE combined with immunotherapy)and observation group(n=38,receiving BACE followed by MW A,which was performed with CT-guided localization of the lung lesion,and immunotherapy in 3-5 days after BACE).Results The surgical success rate in both the 30 patients of the observation group and the 38 patients of the control group was 100％.After treatment,no surgery-related or chemoembolization-related serious complications occurred in both groups.In the control group and the observation group,the mean progression-free survival(PFS)was(5.70±1.61)months and(12.10±0.72)months respectively,the mean overall survival(OS)was(11.80±1.10)months and(13.00±1.13)months respectively.The PFS of the observation group was obviously longer than that of the control group(P＜0.05),and no statistically significant difference in OS existed between the two groups(P=0.255).Conclusion BACE combined with MW A and immunotherapy can effectively control the advanced lung squamous cell carcinoma,it has reliable short-term efficacy when compared with BACE plus immunotherapy,and it can inhibit tumor growth and prolong the PFS of patients,with a trend of extending OS and a satisfactory clinical safety.

Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.

Objective:To explore the short-term efficacy and safety for the new adjuvant therapy of programmed cell protein-1(PD-1)inhibitor combined with Oxaliplatin+Tegafur(SOX)in locally advanced gastric adenocarcinoma. Methods:Retrospective collection of clinical data from 72 locally advanced(stage Ⅲ)gastric adenocarcinoma patients admitted to our gastrointestinal surgery department from January 2020 to July 2020,according to different treatment plans,patients were divided into a control group(n=36)and an observation group(n=36).The control group received SOX chemotherapy regimen,while the observation group received PD-1 inhibitor combined with SOX regimen.Both groups of patients underwent chemotherapy for 3 cycles,and were re-evaluated after resting for 3-4 weeks.Patients with no disease progression and tolerable surgery underwent D2 gastric cancer radical surgery.The overall survival(OS),pathological complete response(pCR)rate,progression free survival period(PFS),RO resection rate,objective response rate(ORR),disease control rate(DCR)and adverse drug reaction were compared between the two groups. Results:The pCR rate,ORR and DCR of the observation group were significantly higher than those of the control group[pCR rate:25％(9/36)vs 5.6％(2/36),x2=5.258,P=0.022;ORR:58.33％(21/36)vs 25.00％(9/36),x2=8.229,P=0.004;DCR:88.89％(32/36)vs 69.44％(25/36),x2=4.1 26,P=0.042].The incidence of adverse reactions such as elevated ALT,elevated AST,and hand foot syndrome during neoadjuvant chemotherapy in the observation group was significantly higher than those in the control group(P＜0.05).The incidence of other adverse reactions was not significantly difference between the two groups of patients(P＞0.05),and there were no neoadjuvant chemotherapy related death events in both groups.The R0 resection rates of the two groups were 97.22％and 91.67％,respectively(x2=1.059,P=0.303).The median OS and median PFS of 72 patients were 36 and 1 3 months,respectively.The 2-year OS rate of the two groups were 82.2％and 71.5％,respectively.Kaplan Meier survival curve analysis showed that the OS rate of the observation group was significantly higher than that of the control group(x2=4.240,P=0.039);the median PFS of the observation group was higher than that of the control group at 14 and 1 1 months,respectively(x2=4.173,P=0.041);COX univariate regression analysis did not identify any factors affecting survival of locally advanced gastric adenocarcinoma. Conclusion:The neoadjuvant treatment of locally advanced gastric adenocarcinoma with PD-1 inhibitor combined with SOX regimen is safe and effective,and the adverse reactions are controllable.

Objective:To explore the detection of potentially pathogenic bacteria (PPB) in the nasopharynx of children with respiratory syncytial virus (RSV) bronchiolitis and the influence of PPB types on disease severity.Methods:In this retrospective cohort study, clinical data of patients hospitalized for RSV bronchiolitis at Department of Respiratory Medicine, Children′s Hospital of Soochow University between January 1, 2017 and December 31, 2019 were retrospectively analyzed.The virus, Mycoplasma pneumoniae and bacteria in nasopharyngeal secretion of children were detected.They were classified into <3 months group, 3-<6 months group, 6 months-<1 year group and 1-2 years group based on the age.In addition, they were further classified into RSV infection group, RSV+ G + group, RSV+ G - group and RSV+ G + + G - group based on detected PPB in the nasopharynx.Comparison of RSV + PPB frequency between groups was performed by Chi- squared test, clinical characteristics were compared by using Mann- Whitney U test. Results:A total of 280 patients with RSV bronchiolitis were included in the study, involving 113 cases (40.4%) with PPB in the nasopharynx.The most-common detection bacterium was Streptococcus pneumoniae.The detection rate of Streptococcus pneumoniae increased with age ( χ2=12.609, P=0.005), while that of Staphylococcus aureus decreased with age ( χ2=8.387, P=0.034). Compared with RSV group, patients in RSV+ G - group had a longer length of stay, higher rate of fever and shortness of breath, higher oxygen supplement and higher C-reactive protein (CRP) (all P<0.05). Compared with RSV group, patients in RSV+ G + group were older, and they had higher rate of fever, higher percentage of neutrophil, lower percentage of lymphocyte and higher CRP (all P<0.05). Conclusions:PPB in nasopharynx can be detected in about 40% of children hospitalized with RSV bronchiolitis, and nasopharynx complicated with PPB infection may affect the severity of RSV bronchiolitis.

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.

Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the genome-wide data of binding sites of the core pluripotency factors (SOX2, OCT4, NANOG, denoted SON), chromosomal interaction and histone modification in hESCs, we identified a potential enhancer of the GLUT1 gene in hESCs, denoted GLUT1 enhancer (GE) element. GE interacts with the promoter of GLUT1, and the deletion of GE significantly reduces the expression of GLUT1, glucose uptake and glycolysis of hESCs, confirming that GE is an enhancer of GLUT1 in hESCs. In addition, the mutation of SON binding motifs within GE reduced the expression of GLUT1 as well as the interaction between GE and GLUT1 promoter, indicating that the binding of SON to GE is important for its activity. Therefore, SON promotes glucose uptake and glycolysis in hESCs by inducing GLUT1 expression through directly activating the enhancer of GLUT1.

Objective To observe the expression of triggering receptor expressed on myeloid cells (TREM),Caspase-3 and interleukin (IL)-6 in optic nerve tissue of ischemic optic neuropathy (ION).Methods Twenty Sprague-Dawley rats were randomly divided into control group and model group,10 rats in each group.The permanent ligation of bilateral internal carotid arteries (BICA) was performed for 14 days to establish subacute ION model as model group.The control group were separated BICA without ligation.The expressions of TREM-1,TREM-2,Caspase-3 and IL-6 in rat retina were detected by reverse transcription PCR and Western blot,respectively.Results Compared with the control group,the expressions of TREM-1,Caspase-3,IL-6mRNA (t=6.058,7.86,6.055) and protein (t=9.671,9.524,14.501) in the optic nerve tissue of the model group were increased,while the expression ofTREM-2 mRNA and protein (t=9.283) was decreased,and the difference was statistically significant (P＜0.05).Conclusion In ischemic optic nerve tissue,TREM-1 mRNA and protein were significantly expressed,the expressions of TREM-2 mRNA and protein decreased significantly.

OBJECTIVE: To explore the molecular etiology for a Chinese family affected with beta-ureidopropinoase deficiency. METHODS: Genomic DNA was extracted from the peripheral blood samples of family members. All exons and flanking intron regions of the UPB1 gene were amplified by PCR and detected by direct sequencing. The pathogenicity of identified mutation was analyzed using Polyphen2 and SIFT software. RESULTS: Compound heterozygous mutations of the UPB1 gene, including c.853G>A (p.A285T) and c.917-1G>A, were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that this novel mutation was damaging. CONCLUSION The compound heterozygous mutations of the UPB1 gene probably underlie the beta-ureidopropinoase deficiency in the infant. Discovery of c.853G>A also enriched the mutation spectrum of the UPB1 gene.
Abnormalities, Multiple ; genetics ; Amidohydrolases ; deficiency ; genetics ; Asian Continental Ancestry Group ; Brain Diseases ; genetics ; China ; Exons ; Humans ; Infant ; Introns ; Movement Disorders ; genetics ; Mutation ; Pedigree ; Purine-Pyrimidine Metabolism, Inborn Errors ; genetics

Objective To study the impacts of B7-H3 molecule on the proliferation of T lymphocytes in different activation conditions and on the secretion of relevant cytokines.Methods Peripheral blood samples were collected from healthy subjects to separate peripheral blood mononuclear cells (PBMC) by Ficoll density gradient centrifugation.T lymphocytes were isolated from some of the PBMCs and purified with T Cell Enrichment Kit.PBMC and purified T lymphocytes were activated by anti-CD3/CD28 monoclonal antibodies (McAb) in vitro.Flow cytometry analysis was used to detect the expression of CD28 and CTLA-4 on T lymphocytes at different time points for further analyzing the activation states of T lymphocytes.On this basis, human B7-H3-Fc fusion protein was added into the mixed co-cultivation system on days 0, 1, 2, 3 and 4, and Hu-Fc fusion protein was used as isotype control.CCK-8 method was performed to detect the proliferation of T lymphocytes in each group.ELISA method was used to detect the secretion of cytokines (IL-2, IL-10 and IFN-γ) and to analyze the immune responses induced by stimulating T lymphocytes at different states of activation with B7-H3.Results B7-H3 molecule significantly inhibited the quiescent T lymphocytes from secreting IL-2 and IL-10, but had no significant impact on IFN-γ secretion.Moreover, it significantly promoted the activated T lymphocytes to secret IL-2 and IFN-γ, but had no obvious impact on IL-10 secretion.Results of the cell proliferation assay showed that B7-H3 molecule inhibited the in vitro proliferation of T lymphocytes in the PBMC, but had no obvious impact on purified T lymphocytes.ConclusionThe regulatory effects of B7-H3 molecule on the immune functions of T lymphocytes vary with the activation states of T lymphocytes.