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Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.

Objectives: To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS)., Methods: A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared., Results: Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor ( P <0.05). There was no significant difference in treatment protocols between the two groups ( P >0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement ( P <0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups ( P >0.05)., Conclusions: Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

Objective: To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults. Methods: Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method. Results: Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P <0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc . BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CI s) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CI s) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions: BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy ( P =0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months ( P =0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL ( HR =3.127, 95% CI 1.057-9.253, P =0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

Objective: To explore the therapeutic effect of transdermal patches containing Cassia seed extract applied at the navel on slow transit constipation (STC) in rats and explore the spectrum-effect relationship of the patches., Method: In a STC rat model established by gavage of compound diphenoxylate suspension for 14 days, the transdermal patches containing low, medium and high doses of Cassia seed extract (41.75, 125.25, and 375.75 mg/kg, respectively) were applied at the Shenque acupoint on the abdomen for 14 days after modeling, with constipation patches (13.33 mg/kg) as the positive control. After the treatment, fecal water content and intestinal propulsion rate of the rats were calculated, the pathological changes in the colon were observed with HE staining. Serum NO and NOS levels and the total protein content and NO, NOS and AChE expressions in the colon tissue were determined. HPLC fingerprints of the transdermal patches were established, and the spectrum-effect relationship between the common peaks of the patches and its therapeutic effect were analyzed., Results: Treatment with the transdermal patches containing Cassia seed extract significantly increased fecal water content and intestinal propulsion rate of the rat models, where no pathological changes in the colon tissue were detected. The treatment also suppressed the elevations of serum and colonic NO and NOS levels and reduction of AChE in STC rats. Twenty-eight common peaks were confirmed in the HPLC fingerprints of 6 batches of Cassia seed extract-containing patches. Analysis of the spectrum-effect relationship showed that autrantio-obtusin had the greatest contribution to the therapeutic effect of the patches in STC rats., Conclusion: The Cassia seed extract-containing patches alleviates STC in rats via synergistic actions of multiple active ingredients in the extract, where autrantio-obtusin, rhein, chrysoobtusin, obtusin, obtusifolin, emodin, chrysophanol, and physcion are identified as the main active ingredients.

Objectives: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA)., Methods: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis., Results: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA ( P <0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA ( P <0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% ( P <0.05)., Conclusions: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Objective: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer., Methods: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients., Results: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues ( P <0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging ( P <0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P <0.001; OS: log-rank=19.71, P <0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P <0.001; OS: log-rank=22.24, P <0.001). Cox multivariate analysis indicated that TNM stage Ⅲ ( HR =2.26, 95% CI : 1.20-5.68), high expression of Tim-3 ( HR =0.80, 95% CI : 0.33-0.91), and low expression of galectin-9 ( HR =1.80, 95% CI : 1.33-4.70) were independent risk factors affecting RFS and OS in patients ( P <0.05)., Conclusion: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10 th and decreased to 0.37 on March 15 th . The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4 th , 2022.

Objectives: Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer., Methods: The clinical data of patients with epithelial ovarian cancer ( n =65) and ovarian benign disease ( n =29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ 2 test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers., Results: The levels of β-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, β-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 ( r s =0.497, P <0.001; r s =0.612, P <0.001; r s =0.358, P =0.003; r s =0.680, P <0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age ( r s =0.322, P =0.009; r s =0.609, P <0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age ( r s =0.256, P =0.040; r s =0.325, P =0.008; r s =0.249, P =0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations., Conclusions: CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age 2 , sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95% CI ) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.

Objective: To investigate the spectrum-effect relationship between the total anthraquinone extract of Cassia seeds and fluorouracil (5-Fu)-induced liver injury in mice and identify the effective components in the extract., Methods: A mouse model of liver injury was established by intraperitoneal injection of 5-Fu, with bifendate as the positive control. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in the liver tissue were detected to investigate the effect of the total anthraquinone extract of Cassia seeds (0.4, 0.8 and 1.6 g/kg) on liver injury induced by 5-Fu. HPLC fingerprints of 10 batches of the total anthraquinone extracts were established to analyze the spectrum- effectiveness of the extract against 5- Fu- induced liver injury in mice and screen the effective components using the grey correlation method., Results: The 5- Fu- treated mice showed significant differences in liver function parameters from the normal control mice ( P < 0.05), suggesting successful modelling. Compared with those in the model group, serum ALT and AST activities were decreased, SOD and T- AOC activities significantly increased, and MPO level was significantly lowered in the mice treated with the total anthraquinone extract (all P < 0.05). HPLC fingerprints of the 31 components in the total anthraquinone extract of Cassia seeds showed good correlations with the potency index of 5-Fu-induced liver injury but with varying correlation strengths. The top 15 components with known correlations included aurantio-obtusina (peak 6), rhein (peak 11), emodin (peak 22), chrysophanol (peak 29) and physcion (peak 30)., Conclusion: The effective components in the total anthraquinone extract of Cassia seeds , including aurantio-obtusina, rhein, emodin, chrysophanol, and physcion, are coordinated to produce protective effects against 5-Fu-induced liver injury in mice.

Objective: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis., Methods: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis., Results: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2 -ΔΔCt ): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2 -ΔΔCt ): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2 -ΔΔCt ): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05)., Conclusions: BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ ( P <0.001) , elevated LDH ( P <0.001) , ECOG score ≥ 2 points ( P =0.005) , and IPI score 3-5 points ( P <0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P <0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P =0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P =0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P =0.018; OS: P <0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P <0.001; OS: P =0.018) , increased LDH levels (PFS: P =0.015; OS: P =0.006) , and multiple extra-nodal involvements (PFS: P <0.001; OS: P =0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P =0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL ( P =0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Fatty liver disease is one of the most prevalent chronic liver disease worldwide and the gut-liver axis is recognized as increasingly prominent in fatty liver disease. Intestinal dysfunction can affect the occurrence or progression of liver disease, therein, validating the critical role of the intestinal immune cells. Enormous literature reported that macrophages, lymphocyte, dendritic cells (DCs) and other immune cells in the gut as well as their subsets may regulate the fatty liver disease progression via different mechanisms, including disruption of intestinal barrier, dysregulation of intestinal lipid transporters and mediating immune cell migration to liver.

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years ( M (IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P <0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P >0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis ( HR =3.06,95% CI :1.52 to 6.16, P =0.039),width of resection margin ( HR =0.56,95% CI :0.32 to 0.99, P =0.044) and adjuvant chemotherapy ( HR =0.51,95% CI :0.29 to 0.91, P =0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group ( P <0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group ( P >0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P <0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

Objective: To analyze the consistency of pepsin assay kit, pepsin IHC, reflux symptom index（RSI） and reflux finding score（RFS） in the diagnosis of laryngopharyngeal reflux disease（LPRD）. Methods: The clinical data of 61 inpatients with laryngeal diseases who were admitted to the Department of Otolaryngology, the First Affiliated Hospital of Kunming Medical University from May 2020 to December 2021 were retrospectively analyzed. The RSI and RFS scores, the Formwitz score of pepsin immunohistochemistry, and the results of pepsin detection kit were recorded. ICC group correlation coefficient and Kappa consistency analysis was used for three detection methods. Results: Among 61 patients, 30 cases were positive and 31 cases were negative for the pepsin test kit, with a positive rate of 49.18%. The positive rate of pepsin immunohistochemistry was 45.90%（28/61）, and the diagnostic agreement rate between the two was 70.49%. The consistency between them was high（ κ =0.409）. The positive rate of RSI and RFS in diagnosing LPRD was 62.30%（38/61）, and the consistency rate was 73.77% with pepsin detection kit. The consistency between them was high（ κ =0.486）. Taking pepsin IHC as the reference standard, the sensitivity, specificity, positive predictive value and negative predictive value of pepsin detection kit were 71.43%（20/28）, 69.70%（23/33）, 66.67%（20/30） and 74.19%（23/31）, respectively. Using RSI and RFS scales as reference criteria, the sensitivity, specificity, positive predictive value and negative predictive value of pepsin detection kit were 89.29%（25/28）, 60.61%（20/33）, 65.79%（25/38） and 86.96%（20/23）, respectively. Analysis of correlation coefficient within ICC group: ICC value was 0.628, 95% confidence interval（0.497-0.741）, the three methods have good consistency. Conclusion: The RSI and RFS scale scores were in good agreement with the pepsin test kit, and the pepsin test kit was also in good agreement with pepsin immunohistochemistry. As a non-invasive diagnostic technique, the pepsin test kit can be widely used in the diagnosis of pharyngeal reflux in combination with pepsin immunohistochemistry and RSI and RFS scale., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites ( P <0.001) and had higher IPI scores ( P =0.013). There was no significant difference in the OS ( P =0.120) and PFS ( P =0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk ( P =0.025) and double expressor (DE) ( P =0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk ( P =0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 ( P =0.006 for OS, P =0.032 for PFS) and MYD88 ( P =0.001 for OS, P =0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Objective: To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling. Methods: Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ 1 and tMφ 2 ) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro . Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ 1 and tMφ 2 . qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ 1 and tMφ 2 after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ 1 and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively. Results: The numbers of intracellular lipid droplet formation in tMφ 1 and tMφ 2 were more than that in Mφ ( P <0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ 1 and tMφ 2 than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ 1 and tMφ 2 decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P <0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (both P <0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (both P <0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (both P <0.05), respectively. MiR-449a was screened from tMφ 1 by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P <0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ 1 and tMφ 2 (all P <0.05). Conclusions: Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.

Increasing studies have provided cognitive and neuron evidence for not only the similarities, but also the differences between physical pain and social pain in the brain basis. Comparing the similarities and differences of the brain basis of physical pain and social pain helps us to clarify the mechanism of the occurrence and change of pain, and provide theoretical evidence for clinical pain treatment. In this review, we summarized studies to delineate the brain mechanisms of physical pain and social pain. Through the review of existing studies, we found that both physical pain and social pain can invoke the same brain regions that process emotional experience (the dorsal anterior cingulate cortex, anterior insula), emotion regulation (lateral prefrontal cortex) and somatosensory (the posterior insula, secondary sensory cortex). However, the voxel-level activated patterns of physical and social pain differ in the same brain region (dorsal anterior cingulate gyrus, dorsolateral prefrontal cortex, etc.), and the overlapping brain regions (for example, ventrolateral prefrontal cortex) have varied effect on these two types of pain. In addition, studies have shown that the brain activation pattern for social pain may be influenced by the experimental paradigm. Future studies should actively adopt a data-driven way to examine the brain basis of physical pain and social pain, especially the nerve activation mode, aiming to consummate the theory of pain.

Helminth infections may trigger host innate and adaptive immune responses. Group 2 innate lymphoid cells (ILC2) are an important factor involved in type 2 immune responses, and produce a large number of T helper 2 cell (Th2) cytokines following stimulation by interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), which play a critical role in parasite clearance and tissue repair. Following helminth infections, autocrine factors, mast cells, enteric nervous system and Th2 cells have been recently found to be involved in regulation of ILC2. Unraveling the role of ILC2 in immune response against helminth infections is of great value for basic research and drug development. This review summarizes the research progress on ILC2 and its role in helminth infections.

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Objective: To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection., Methods: DOX-loaded PELA staple fibers (F DOX ) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of F DOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (G CA4P /F DOX ). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of G CA4P /F DOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments., Results: The average length of F DOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro . Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with G CA4P /F DOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm 3 in G CA4P /F DOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G 4A4P /F DOX ., Conclusion: As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

Objective: To explore the genotype-phenotype correlation of a case with GM1-gangliosidosis caused by compound heterogenic variants in GLB1., Methods: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Trio-based whole-exome sequencing (WES) was performed for the family and suspected mutation was verified by Sanger sequencing., Results: The proband, a 2-year-3-month old Chinese girl, presented with psychomotor deterioration, absent speech, intellectual disabilities and behavior problem. Trio-based WES has identified compound heterozygosity for 2 variants in the GLB1 gene: NM&#95;000404.2:c.1343A>T, p.Asp448Val and c.1064A>C, p.Gln355Pro (GRCh37/hg19),which was inherited from the mother and father, respectively. Homozygous or compound heterozygous pathogenic variants in GLB1, encoding β-galactosidase, are responsible for GM1-gangliosidosis,an autosomal recessive lysosomal storage disorder characterized by variable degrees of neurodegeneration and skeletal abnormalities. The p.Asp448Val variant has been classified as pathogenic for GM1 gangliosidosis in medical literatures for the reason that functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable β-galactosidase activity compared to wild type GLB1. The p.Gln355Pro variant has not been reported in literatures or database. The variant is highly conserved residue (PM1), and was not found in either the Genome Aggregation Database or the 1000 Genomes Project (PM2) and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3). Next, the β-galactosidase activity of the patient's peripheral blood leukocytes was determined by fluorescent method. The result was 0.0 nmol/mg. It showed that the p.Gln355Pro variant also resulted in loss of β-galactosidase activity, thus the variant was classified into clinical pathogenic variant., Conclusion: Our study expands the mutational spectrum of the GLB1 gene and provides genetic counseling for the family.

Objective: To develop and validate a risk prediction model of treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP)., Methods: We retrospectively analyzed the data of patients undergoing peritoneal dialysis (PD) in 3 dialysis centers in Jilin Province who developed PDAP between January 1, 2013 and December 31, 2019. The data collected from the Second Hospital of Jilin University and Second Division of First Hospital of Jilin University) were used as the training dataset and those from Jilin Central Hospital as the validation dataset. We developed a nomogram for predicting treatment failure using a logistic regression model with backward elimination. The performance of the nomogram was assessed by analyzing the C-statistic and the calibration plots. We also plotted decision curves to evaluate the clinical efficacy of the nomogram., Results: A total of 977 episodes of PDAP were included in the analysis (625 episodes in the training dataset and 352 episodes in the validation dataset). During follow-up, 78 treatment failures occurred in the training dataset and 35 in the validation dataset. A multivariable logistic regression prediction model was established, and the predictors in the final nomogram model included serum albumin, peritoneal dialysate white cell count on day 5, PD duration, and type of causative organisms. The nomogram showed a good performance in predicting treatment failure, with a C-statistic of 0.827 (95% CI : 0.784-0.871) in the training dataset and of 0.825 (95% CI : 0.743-0.908) in the validation dataset. The nomogram also performed well in calibration in both the training and validation datasets., Conclusion: The established nomogram has a good accuracy in estimating the risk of treatment failure in PDAP patients.

Objective: To explore the genetic basis for a child featuring complex cortical dysplasia and other brain malformations (CDCBM3)., Methods: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out for the family trio. Suspected variant was verified by Sanger sequencing., Results: The proband, a 1-year-and-2-month old Chinese boy, had presented with motor developmental delay, lissencephaly, severe cognitive impairments, absent speech and congenital laryngomalacia. WES revealed that he has harbored a heterozygous missense variant of the KIF2A gene, namely NM&#95;001098511.2: c.952G>A, p.Gly318Arg (GRCh37/hg19). The highly conserved residue is located around the ATP nucleotide-binding pocket in the kinesin motor domain (PM1). The variant was not found in the Genome Aggregation Database and the 1000 Genomes Project (PM2), and was predicted to be deleterious on the gene product by multiple in silico prediction tools (PP3). This variant was unreported previously and was de novo in origin (PS2). Based on the ACMG guidelines, it was categorized as likely pathogenic (PS2+PM1+PM2+PP3). Furthermore, the congenital laryngomalacia found in our patient was absent in previously reported CDCBM3 cases., Conclusion: The novel variant of the KIF2A gene probably underlay the disorders in the proband. Above finding has expanded the phenotypic and mutational spectrum of CDCBM3.

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95% CI :3.27%-4.85%), it increased to 5.53% (95% CI : 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95% CI :4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.

Objective: To understand the social support, social network, and sexual behavior characteristics of foreigners living in Guangzhou, analyze factors relating to aspects of online social interactions and sexual behaviors of foreigners in Guangzhou, and provide references for targeted HIV intervention services for foreigners. Methods: A cross-sectional survey (both online and offline), among those who met the inclusion criteria was conducted between November 2019 and January 2020. Data were collected on demographics, social support, online social interactions, sexual behaviors, and so on. Statistics were compiled to analyze the factors that may influence casual sexual behaviors. Results: A total of 434 participants were included in the study (241 offline and 193 online). The majority of the participants were male 68.4% (297/434), age (31.0±8.8) years old, African 79.0% (343/434), business people 46.5% (202/434), students 48.2% (209/434), who have business partners and family members in China were 59.4% (258/434) and 28.1% (122/434) separately. They also had the following features: less than 10 close friends 57.1% (248/434); spend 1-3 hours on social applications per day 43.3% (188/434), had casual sexual behaviors in the last 3 months 15.2% (55/363). Multiple logistic regression model analysis showed that compared with those who used social applications for less than 1 hour per day, participants who used social applications for more than 6 hours per day were more likely to have casual sexual behaviors in the last 3 months ( OR =3.63, 95% CI : 1.31-10.08). Conclusions: Participants who used social applications for a longer period every day were more likely to have casual sexual behaviors among foreigners in Guangzhou. Good use of social applications for health promotion and education of HIV can increase the health awareness of foreigners in China.

Objective: To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene., Methods: Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing., Results: The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM&#95;003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported., Conclusion: This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.

Objective: To evaluate the dynamic changes of pulmonary arterial pressure (PAP) and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome (ARDSp/ARDSexp)., Methods: An observational study was conducted. A total of 128 neonates with ARDS admitted to neonatology department of the Affiliated Yancheng Hospital of Southeast University Medical College from January 2016 to December 2020 were enrolled, with 67 neonates in ARDSp group and 61 neonates in ARDSexp group. After starting mechanical ventilation, oxygenation index [OI, OI = mean airway pressure (Pmean)×fraction of inspired oxygen (FiO 2 )/arterial partial pressure of oxygen (PaO 2 )×100], PAP, cardiac function parameters [cardiac index (CI), left ventricular ejection fraction (LVEF), right ventricular Tei (RV-Tei)], and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups; the incidence of pulmonary arterial hypertension [PAH, pulmonary artery systolic pressure (PASP) was more than 35 mmHg (1 mmHg = 0.133 kPa) or more than 2/3 of the systolic blood pressure of the body circulation] of neonates was recorded. The correlation between PAP and NT-proBNP was analyzed by Pearson correlation method. The dynamically changes in PAP and RV-Tei before and after using Milrinone in neonates with ARDSp and ARDSexp combined with moderate-severe PAH (PASP 50-69 mmHg was moderate, and PASP ≥ 70 mmHg was severe) were observed. The duration of mechanical ventilation, total length of hospital stay and prognosis were recorded; Kaplan-Meier survival curve was drawn to analyze the 28-day survival of the two groups., Results: The occurrence rate of PAH in ARDSp group was significantly higher than that in ARDSexp group (97.01% vs. 70.49%, P < 0.01). OI, PAP, NT-proBNP and RV-Tei were also higher [OI: 17.61±6.12 vs. 11.04±5.35, PAP (mmHg): 64.27±9.54 vs. 53.61±6.47, NT-proBNP (ng/L): 23 126.32±1 485.14 vs. 18 624.24±1 647.15, RV-Tei: 0.61±0.22 vs. 0.52±0.19, all P < 0.05], but there was no significant difference in CI or LVEF between the two groups. Pearson correlation analysis showed that PAP was significantly positively correlated with NT-proBNP (r = 0.918, P < 0.01). There were 97 ARDS neonates with moderate-severe PAH with 63 in ARDSp group and 34 in ARDSexp group. Both PAP and RV-Tei in the two group showed a decreasing trend with the prolongation of Milrinone treatment, the decrease was more significant in the ARDSexp group compared with ARDSp group, the difference was statistically significant at 72 hours of treatment [PAP (mmHg): 38.42±8.95 vs. 45.67±13.32, RV-Tei: 0.58±0.19 vs. 0.61±0.13, both P < 0.05]; there was no significant difference in PAP or RV-Tei before extubation between the two groups. The duration of mechanical ventilation and the total length of hospital stay in ARDSp group were significantly longer than those in ARDSexp group [duration of mechanical ventilation (days): 10.12±1.36 vs. 6.31±1.31, total length of hospital stay (days): 16.52±3.25 vs. 13.12±3.57, both P < 0.01]. Kaplan-Meier survival curve showed that neonate in ARDSp group had a significantly lower 28-day cumulative survival rate as compared with ARDSexp group (82.09% vs. 95.01%; Log-Rank test: χ 2 = 5.062, P = 0.025)., Conclusions: Both PAP and RV-Tei were significantly increased in neonates with ARDS, PAP in neonates with ARDSp were significantly higher than that in neonates with ARDSexp. Dynamic monitoring of PAP and RV-Tei can reflect the severity of ARDS in neonates, and targeted intervention of pulmonary surfactant combined with Milinone for improving oxygenation and reducing PAP is one of the effective methods for the treatment of PAH.

Objectives: To study the feasibility of ArcCHECK-3DVH system in dosimetric verification for stereotactic body radiaotherapy (SBRT) with flattening filter free (FFF) model., Methods: SBRT treatment plans for 57 patients were introduced into ArcCHECK phantom and recalculated. The calculated dose distribution of treatment planning system and the measured dose distribution of ArcCHECK phantom were compared by γ analysis. Then the 3 dimensional dose distribution of target and organs at risk was reconstructed by 3DVH software. The reconstructed dose and calculated dose with treatment planning system (TPS) were compared, and the dose volume γ pass rate and deviation of dose volume parameters to the target and organs at risk were quantitatively valuated., Results: Based on the threshold criteria (3%, 3 mm, 10%), namely the deviation of measuring points between the planned value and the measured value was less than 3%, and the proportion of points with similar values in the plane or sphere with the center of the point and the radius of 3 mm was 10%, the relative and absolute dose pass rates of SBRT treatment plans in ArcCHECK system via γ analysis were greater than 95%. Based on the stricter threshold criteria (2%, 2 mm, 10%), the relative and absolute dose pass rates of SBRT treatment plan in ArcCHECK system via γ analysis were about 93%. In 3DVH dose verification, the γ pass rate of target and organs at risk was exceed 97%, and the deviations in 3DVH of the target and organs at risk were less than ±5%., Conclusions: The ArcCHECK-3DVH system in dose verification can provide more comprehensive dose distribution information to reasonably evaluate the SBRT plan, with more significance for guiding clinical treatment.

The widespread use of antibiotics in the aquaculture industry has caused antibiotic resistance genes (ARGs) pollution. Metagenomics technology was used to detect and analyze the relative abundance of ARGs and microbial community structure in a fishery reclamation mining subsidence area. A total of 29 ARGs were detected, and bacA had the highest relative abundance in all the samples, reaching 1.96×10 -5 -1.19×10 -4 . The relative abundance of sulfonamide and tetracycline ARGs in sediments was relatively high and the relative abundance of multidrug ARGs in well water was relatively high. Proteobacteria was the most dominant bacterial phylum in all the samples, and Chloroflexi and Euryarchaeota were relatively abundant in the sediments. Thiobacillus was the most dominant bacterial genus in the sediments, and Acinetobacter and Pseudomonas were the dominant bacterial genera in the well water. The correlation analysis between the ARGs and microorganisms showed that the genera and ARGs were mainly correlated to a moderate degree, and multiple genera had significant positive correlations with ARGs. The distribution of ARGs was affected by the structure of the microbial community. The sediments and well water in the fishery reclamation mining subsidence area were both contaminated by ARGs, and corresponding control measures should be strengthened to protect the regional environment.

Objective: To compare the postoperative outcomes and urinary continence recovery time between standard robotic-assisted laparoscopic radical prostatectomy (RARP) and Retzius-sparing robotic-assisted laparoscopic radical prostatectomy (RsRARP). Methods: A total of 92 patients with low to intermediate-risk prostate cancer who underwent RARP ( n =52) and RsRARP ( n =40) in Sir Run Run Shaw Hospital from October, 2016 to January, 2018 were retrospectively reviewed. Perioperative data (operative time, estimated blood loss, complications, postoperative staging, postoperative Gleason score) and surgical outcomes (rate of margin positive, urinary continence recovery time) of RARP and RsRARP group were comparatively analyzed. Results: All 92 cases were successfully performed with robot. RARP group had a significantly shorter mean operative time when compared with that in RsRARP group ((103±23) min vs (130±26) min, P <0.05). The two groups had comparable estimated blood loss ((100±54) ml vs (103±64) ml, P >0.05), rate of postoperative infection (5.8% (3/52) vs 5.0% (2/40), P >0.05) and rate of postoperative urine leakage (3.8%(2/52) vs 2.5%(1/40), P >0.05). The two groups had a comparable rate of margin positive (7.7%(4/52) vs 12.5%(5/40), P >0.05). Compared with RsRARP group, the RARP group had a lower rate of urinary continence recovery immediately after the catheter removing at 1 week, 1 month and 3 months after the operation (all P >0.05). The two group had a comparable rate of urinary continence recovery at 6 months after the operation ( P >0.05). Conclusion: The RsRARP technique has a good tumor control and obvious advantage of early urinary continence recovery compared with the standard RARP technique. RsRARP technique is safe and effective for the treatment of localized prostate cancer.

Objective: To analyze the influencing factors of HIV testing behavior among foreigners in Guangzhou, and provide a reference for promoting HIV testing and intervention services in foreigners. Methods: A cross-sectional survey was conducted from November 2019 to January 2020 among 230 eligible foreigners selected in Guangzhou through convenient sampling method in the form of one-to-one questionnaire interview, HIV testing behaviors and related influencing factors were described and analyzed with χ (2) test and multivariate logistic regression model. Results: A total of 230 foreigners were included in the study, in whom 156 were males (67.8%), 217 were from Africa (94.3%), 138 (60.0%) were with education level of university and above, 169 (73.5%) were in business, 47 (20.4%) were students, 132 (57.4%) had cumulative residence >12 months in Guangzhou and 113 (49.1%) had health examination in China in the past 6 months. In these foreigners, the rate of AIDS-related knowledge awareness was 76.0%, the proportion of condom use in the last sex was 39.6%(89/225) and 47.8%(110/230) received HIV tests in the past 3 months. Multivariate logistic regression analysis showed, the influencing factors of HIV testing behavior in the past 3 months included cumulative residence ≤12 months (compared with cumulative residence >12 months, OR =3.12, 95 %CI : 1.49-6.56), health examination in China in the past 6 months (compared to those who had not, OR =2.53, 95 %CI : 1.17-5.48), awareness of HIV testing and consulting service in Guangzhou (compared with those who had no awareness, OR =3.65, 95 %CI : 1.71-7.78). Conclusions: Some foreigners in Guangzhou had relatively low rates of HIV testing and condom use. Those who pay attention to their own health status and know well about HIV testing and consulting services are more likely to receive HIV testing, foreigners in Guangzhou should be encouraged to receive HIV testing. Their self-testing awareness should be improved.

Objective: To identify the risk factors and clinical features associated with the interstitial pneumonia in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) or rituximab, cyclophosphamide, liposomal doxorubicin, vincristine and prednisone (RCDOP) regimens. Methods: A retrospective study was conducted in 836 patients with DLBCL admitted to the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 114 patients were treated with RCDOP regimen. Using the method of propensity score matching according to age, gender, IPI score of patients, 114 patients treated with RCHOP regimen were selected as controls. Clinical data, including comorbidities, gender, age, B symptoms, international prognostic index (IPI) score, disease stage, serum lactic dehydrogenase (LDH) and β(2) microglobulin (β(2)-MG) level were collected and the risk factors of interstitial pneumonia were further analyzed. Results: The interstitial pneumonia developed more frequently in RCDOP group than RCHOP group (28.95% vs 2.60%, P <0.01) . As the dose of liposomal doxorubicin elevated from 25-30 mg/m(2) to 35-40 mg/m(2), the incidence of interstitial pneumonia accordingly increased from 17.30% to 38.71% ( P <0.05) . By multivariate analysis, disease stage was an independent factor of interstitial pneumonitis. Conclusions: Front line regimens containing liposomal doxorubicin in DLBCL patients link to a higher incidence of dose-dependent interstitial pneumonia. Prevention and surveillance should be emphasized in future studies.

Objective: To investigate the effect of optimized preoperative dietary management on enhanced recovery in patient with consecutive operation of robot-assisted radical prostatectomy(RARP) at night. Methods: Forty patients undergoing consecutive operation of robot-assisted radical prostatectomy at night in the department of urology in our hospital from Jun 2018 to March 2019 were divided into two groups, 23 patients in the study group and 17 patients in the control group. The control group followed the traditional fasting program at 24∶00 p.m. the day before the surgery. In the study group, the preoperative fasting procedure was optimized. The fasting time, water deprivation time, intravenous infusion volume, scores of hunger and thirst, blood glucose level, length of postoperative hospital stay and adverse reactions were compared between two groups. The level of hunger and thirst were evaluated using the Likert score. Results: The preoperative fasting time and water deprivation time of the study group and the control group were (11.9±4.4 vs 19.3±4.8) h and (6.0±2.9 vs 19.3±4.8) h, respectively ( P< 0.01). The infusion volume of study group was (406.5±310.5) ml and that of control group (744.1±443.0) ml, the difference was statistically significant ( P< 0.01). The hunger and thirst scores of the study group were lower than those of the control group before surgery, and the postoperative hospital stay was shorter than the control group ( P< 0.05). Conclusion: The optimized preoperative dietary management shortens fasting and water deprivation time, reduces the intravenous infusion volume, relieves the hungry and thirsty in patients with consecutive operation of robot-assisted radical prostatectomy at night.

Objective: To observe whether the history of solid tumors affects the treatment response and survival situation of patients with diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective study was conducted in 836 patients with DLBCL who were treated in the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 34 DLBCL patients who had the history of solid tumors were classified into double cancer group. From 802 patients without history of solid tumors, 68 DLBCL patients were selected as control group, using 1∶2 matching on propensity scores for age, gender, IPI score and etc. All patients included in the study had follow-up interviews through medical record and telephone for mortality from any cause. Treatment response and 3-year overall survival (OS) and progression-free survival (PFS) of two groups were analyzed. Results: The complete remission rates after RCHOP (Rituximab+Cyclophosphamide+Vincristine+Adriamycin 50 mg/m(2) or Epirubicin or Liposome Adriamycin+Prednisone) regimen were 79.4% and 67.6% in the double cancer group and the control group, respectively ( P =0.210) . Among the 102 patients, 6 patients died in the double cancer group while 24 patients died in the control group and the median survival time of both two groups were not reached. The 3-year OS were (74.7±9.5) % and (63.5±6.1) % ( χ (2)=2.791, P =0.095) , while 3-year PFS were (72.1±8.8) % and (54.3±6.4) % ( χ (2)=1.400, P =0.237) in the double cancer group and the control group, respectively. Conclusion: The history of solid tumors didn't affect DLBCL patients' treatment response and short-term survival.

Objective: To investigate the pathogenesis of acne vulgaris, and to provide new ideas for non-antibiotic therapy for acne vulgaris.
 Methods: Normal human epidermal keratinocyte (NHEK) was exposed to Propionibacterium acnes (P. acnes) [multiplicity of infection (MOI)=10, 20, 30] for 12, 24, or 36 hours. The enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to detect the protein and mRNA of IL-1β in NHEK. Three groups were set up as follows: A negative control group (no NHEK pretreatment), a positive control group (P. acnes was used to stimulate NHEK), and a siRNA group (pretreated NHEK with siRNA). ELISA, real-time PCR, and Western blotting were used to detect the protein, mRNA of IL-1β and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) in NHEK.
 Results: IL-1β of NHEK in the positive control group was significantly increased in a time and dose-dependent manner compared with the negative control group (P<0.05). After pretreating NHEK with siRNA, IL-1β level was decreased compared with the positive control group, but it was higher than that in the negative control group (P<0.05).
 Conclusion: P. ances can stimulate NHEK to secrete IL-1β, and the process is possibly involved in NLRP3. The inflammatory response induced by P. ances could be inhibited by suppressing the activity of NLRP3.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Objective: To explore the clinical characteristics of follicular lymphoma (FL) in the era of rituximab combined with chemotherapy and the prognostic significance of the follicular lymphoma international prognostic index (FLIPI), follicular lymphoma international prognostic index 2 (FLIPI2), international prognostic index (IPI), revised international prognostic index (R-IPI), National Comprehensive Cancer Network international prognostic index (NCCN-IPI) among Chinese patients. Methods: 229 FL patients who were treated initially with rituximab combined with CHOP-like (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy from November 2008 to April 2018 were analyzed retrospectively and all were scored by the above clinical index. Univariate and multivariate survival analysis were performed on 201 patients who completed the treatment and were followed regularly. Results: In the univariate survival analysis, age>60 years, hemoglobin<120 g/L, elevated serumβ(2)- macroglobulin, involvement of bone marrow and elevated CRP were the risk prognostic factors for overall survival (OS) and progression free survival (PFS). Moreover, the analysis of the OS and PFS between rituximab (R) maintenance (RM) group and non-maintenance (non-RM) group showed that the OS and PFS of RM group were better than those of non-RM. In the multivariate analysis of OS, hemoglobin<120 g/L, involvement of bone marrow, elevated CRP and non-RM were independent prognostic factors. In the multivariate analysis of PFS, hemoglobin<120 g/L, CRP and non-RM were independent prognostic factors. When FLIPI2 was included in the multivariate analysis, CRP and FLIPI2 were independent prognostic factors in both OS and PFS, and non-RM was independent prognostic factors in PFS. Conclusion: FLIPI2 is the better risk stratification in FL patients in the era of rituximab.

Objective: To determine the role of inlerleukin-18 (IL-18) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) in acne vulgaris., Methods: We used propionibacterium acnes (P.acnes) suspensions [multiplicity of infection (MOI)=0, 10, 20, 30] to stimulate normal human epidermal kerationocytes (NHEKs) for 12, 24, and 36 h, respectively. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the protein level of IL-18. Real-time quantitative PCR (real-time PCR) was adopted to detect the mRNA of IL -18.The NHEKs were divided into three groups: ① siRNA group: NHEKs were pretreated with siRNA for 36 h, followed by 36 h exposure to MOI=30 of P.ances suspensions; ② blank control group: NHEKs free from siRNA transfection and P.ances suspensions; ③ positive control group: NHEKs free from siRNA transfection were exposed to P.ances suspensions (MOI=30).The expression of NLRP3 was detected by Western blot., Results: The expressions of protein and mRNA of IL-18 increased with exposure to P.ances suspensions in a dose responsive way ( r >0.75, P <0.05), with the peak effects showing for MOI=30 at 36 h. The expression of IL-18 decreased in the siRNA group compared with the positive control, but was still higher than that of the blank group( P <0.05)., Conclusion: P.ances stimulates NHEK cells to secrete IL-18. The process possibly requires the involvement of NLRP3., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: To study the feasibility of ArcCheck verification system in dosimetric verification for stereotactic radiotherapy (SRT) the stereotactic radiotherapy (SRT) with flattening filter free (FFF) model.
 Methods: A total of 76 cases under SRT treatment plans were introduced into ArcCheck phantom and recalculated. Threshold criteria was set as (3%, 3 mm, 10%) or (2%, 2 mm, 10%). The calculated dose distribution and the measured dose distribution of ArcCheck phantom were compared by means of distance to agree (DTA) and Gamma analysis method respectively.
 Results: Based on the threshold criteria (3%, 3 mm, 10%), the relative and absolute mean pass rates of SRT treatment plans by DTA and Gamma analysis were greater than 95%. Based on the threshold criteria (2%, 2 mm, 10%), the relative and absolute mean pass rates of SRT treatment plan by DTA and Gamma analysis were about 90%. The dose pass rate of Gamma analysis method was slightly higher than that of DTA analysis method (P<0.001).
 Conclusion: The ArcCheck verification system is a rapid and accurate method for SRT dose verification, and discrepancies are found in different analysis methods.

Objective: To analyze and summarize the surgical experience of robotic-assisted laparoscopic partial nephrectomy (RAPN) for treating renal hilar tumors, and assess the efficacy and safety of this surgery. Methods: The clinical data of 22 renal hilar tumor patients who underwent RAPN in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine between September 2015 and September 2017 was analyzed. The patients included 19 males and 3 females, with an average age of (55.6 ±13.0) years old and the age range was 28-75 years. In 13 cases, the tumors were in left kidney, and 9 in the right. There were 10 large tumors (>4 cm diameter), the average tumor size was (3.7±1.9) cm. Preoperative glomerular filtration rate was normal in all cases. Results: The surgery was successfully finished in all of the cases, with no conversion to open surgery. The mean duration of the surgery was 80-270 min, with an average of (134.7±44.5) min. The blood loss was 80-500 ml, with an average of (135.9±130.7) ml, and none of the cases needed intraoperative blood transfusion. The warm ischemia time was 8-25 min, with an average of (18.2±4.0) min. The postoperative length of hospitalization was 7-23 d, with an average of (11.5±4.1) d. Serious gross hematuria occurred in 1 patient, and paroxysmal atrial fibrillation occurred in 1 patient after surgery. The post-operative pathology showed renal clear cell carcinoma in 18 cases, papillary renal cell carcinoma in 2 cases, chromophobe cell carcinoma in 1 case and well differentiated neuroendocrine tumor in 1 case. The tumor resection margin was negative in all cases. Neither local recurrence nor metastasis was observed during a follow-up of 1 to 15 months. Renal function of all the patients was in normal range. Conclusion: RAPN is a safe, useful approach and a minimally invasive operation for treating renal hilar tumors and it owns crucial advantages in complete and accurate resection of the renal hilar tumors and the reconstruction of the kidney.

Objective: To investigate the efficacy of single-hand four-needle suture with sled-shaped needle three-tail fixed stitch in closure of pesudohernia sac of direct hernia under transabdominal preperitoneal (TAPP) inguinal hernia repair., Methods: A randomized controlled trail was conducted on adult patients with unilateral direct inguinal hernia undergoing laparoscopic TAPP repair from January 2014 to January 2018 at the Sixth Affiliated Hospital of Sun Yat-sen University. A total of 156 patients were enrolled prospectively in the study and were randomly divided into single-hand four-needle suture group (trial group, 76 cases) and traditional tacking group (control group, 80 cases). In trial group, sled-shaped needle three-tail knot-free stitch was applied to the continuous four-needle suture. The sled-shaped needle three-tail fixed stitch was made as follows: straighten the tail of a 3-0, 1/2-circle looper VICRYL Rapide into a sled shape; use suture overlap method to make and tighten a single knot; thread the end of the needle into the single knot loop;knot two ends of the thread next to the first knot; tighten the second knot, leaving about 12 cm to the end of the needle;cut the end of the loop (leaving about 0.6 cm) and the other end of the thread(leaving about 1.5 cm). In the control group, a hernia repair tack was used to fix the pseudohernia sac on pectineal ligament. This study was approved by the Hospital Ethics Committee(approval number: L2014ZSLYEC-016). Operation time, pseudoherina sac closure time, hospitalization cost, morbidity of postoperative complication, VAS score and postoperative recurrence were compared between two groups., Results: All the patients completed operations successfully. There were no significant differences between trial group and control group in age [(60.2±0.4) years vs. (61.1±0.7) years)], gender (male ratio 93.4% vs. 92.5%), BMI [(25.1±0.2) kg/m 2 vs. (24.9±0.2) kg/m 2 ], defection area [(16.1±0.4) cm 2 vs. (15.7±0.7) cm 2 ] (all P > 0.05). As compared to control group, trial group had longer operative time[(34.2±1.9) minutes vs. (30.3±1.1) minutes, t=5.484, P=0.045], longer closure time of psudohernia sac [(4.2±0.5) minutes vs. (1.8±0.7) minutes, t=7.423, P=0.031], but lower VAS score (3.2±0.1 vs. 5.3±0.6, t=-3.186, P=0.015) and lower total cost [(9 897.3±104.4) yuan vs. (12 325.6±169.7) yuan, t=-3.972, P=0.023]. No severe complication and death were found in either groups intra-operatively and postoperatively. No mesh infection and relapse occurred during postoperative follow-up of 1-24 (12.0±1.2) months. During follow-up, seroma occurred in 2 cases (2.6%) of trial group and 3 cases (3.8%) of control group without significant difference (χ 2 =1.284, P=0.799), and all were absorbed and disappeared within 30 days after local application of mirabilite., Conclusion: Compared to tack fix method, single-hand four-needle suture with sled-shaped needle three-tail fixed stitch can effectively close pseudohernia sac, reduce hospitalization cost and ameliorate postoperative pain in TAPP repair, which is worth promotion.

The impact of different aeration positions on startup and operation of the continuous flow CANON granular sludge process was considered by inoculating flocculent ANAMMOX activated sludge at room temperature (25±1)℃ in two sets of AUSB reactors. The aeration unit of R1 was installed 0.3 m above the base, while the aeration unit of R2 was set at the bottom. R1 and R2 successfully developed the granule CANON process on the 43rd d and 56th d, respectively. The mean particle diameter of R1 granular sludge increased to 214.79 μm, and the eigenvalue (△NO 3 - -N/△TN) was maintained at 0.128; whereas, the granular sludge size of R2 rose to 205.27 μm with an eigenvalue maintained at 0.129. The nitrogen loading rate (NLR) was gradually increased in the low ammonia-nitrogen (90 mg·L -1 ) wastewater within R1 and R2. This was more beneficial in R1, resulting in the persistent growth of CANON granular sludge and the enhancement of the systematic nitrogen removal rate (NRR). The average particle diameter of R1 rose to 507.46 μm in 88 d, while NRR reached up to 0.277 kg·(m 3 ·d) -1 . R2 granule sludge particle size was 467.72 μm after 108 d of cultivation, and achieved a 0.243 kg·(m 3 ·d) -1 NRR, which was 87.73% of that in R1. During the course of steady operation, the specific anoxic/aerobic mode of R1 effectively suppressed NOB microbial activity, the eigenvalue remained around 0.127±0.003, and the NRR of R1 was maintained at about (0.262±0.019) kg·(m 3 ·d) -1 . However, NOB was propagated observably in the continuously aerobic R2, whose eigenvalue rose to 0.136±0.004, while NRR was merely (0.231±0.015) kg·(m 3 ·d) -1 after 125 d of long-term operation. During the whole experiment period, the intermediate-setting aerated AUSB accelerated the formation of CANON granular sludge evolving from flocculent ANAMMOX sludge, and better nitrogen removal performance and operational stability were achieved.

Synchronization analysis of electroencephalogram (EEG) and electromyogram (EMG) could reveal the functional corticomuscular coupling (FCMC) during the motor task in human. A novel method combining Gabor wavelet and transfer entropy (Gabor-TE) is proposed to quantitatively analyze the nonlinearly synchronous corticomuscular function coupling and direction characteristics under different steady-state force. Firstly, the Gabor wavelet transform method was used to acquire the local frequency-band signals of the EEG and EMG signals recorded from nine healthy controls simultaneously during performing grip task with four different steady-state forces. Secondly, the TE of local frequency-band was calculated and the unit area index of the transfer ( A TE ) was defined to quantitatively analyze the synchronous corticomuscular function coupling and direction characteristics under steady-state force. Lastly, the effect of EEG and EMG signal power spectrum on Gabor-TE analysis was explored. The results showed that the coupling strength in the beta band was stronger in EEG→EMG direction than in EMG→EEG direction, and the A TE values in the beta band in EEG→EMG direction decreased with the force increasing. It is also shown that the difference in TE values of gamma band present a varying regularity as the increase of force in both directions. In addition, EMG power spectrum was significantly correlated with the result of Gabor-TE inspecific frequency band. The results of our study confirmed that Gabor-TE can quantitatively describe the nonlinearly synchronous corticomuscular function coupling in both local frequency band and information transmission. The analysis of FCMC provides basic information for exploring the motor control and the evaluation of clinical rehabilitation.

Objective To construct the expression vector of the fusion protein of apolipoprotain B mRNA editing enzyme catalytic polypeptide-like 3A (APOBEC3A) and hepatitis B virus core proteins (HBc) with different sequences, and identify its expression, intracellular localization and cytosine deamination activity. Methods The APOBEC3A gene and the coding sequence of HBc and four kinds of truncated HBc containing C-termimal domain were amplified by PCR. The APOBEC3A with full-length HBc antigen or four kinds of truncated HBc were cloned into a eukaryotic expression vector pcDNA3.0 by In-Fusion method, and confirmed by DNA sequencing. The recombinants were then transfected into HEK293T cells. The expression and localization of the fusion proteins were detected by Western blotting and immunofluorescence cytochemistry. The cytosine deamination activity was analyzed by electrophoresis on a urea denaturing polyacrylamide gel. Results Five kinds of fusion protein were expressed in HEK293T cells successfully, and the expression of the vectors containing the truncated HBc were higher than that of the APOBEC3A-HBc vector containing the full-length HBc. The fusion protein of APOBEC3A-HBc was mainly expressed in the cytoplasm of HEK293T cells, and the fusion proteins of APOBEC3A-HBc144S, APOBEC3A-HBc144E, APOBEC3A-HBc144AAA, APOBEC3A-HBc144A were expressed mainly in the nuclei of HEK293T cells. The cytosine deamination activity of the fusion proteins containing the truncated HBc was higher than that of the fusion protein APOBEC3A-HBc. Conclusion The fusion protein expression vectors of APOBEC3A and HBc with different lengths and sequences have been constructed successfully. The expressing ability, intracellular localization and cytosine deamination activity are obviously different between the fusion protein APOBEC3A-HBc and the fusion proteins containing the truncated HBc.