[The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection].

Objectives: This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs). Methods: The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit). Results: All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively. Conclusions: This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

[Investigate the thyroid function of radiation workers and analysis of influence factors].

Objective: To analyze the thyroid condition and influencing factors of radiation workers, and to provide scientific basis for radiation protection management. Methods: In April 2020, 4308 radiation workers from October 1, 2017 to September 30, 2019 were collected for occupational health examination in Hangzhou Occupational Disease Prevention and Treatment Hospital, the data included basic information, Thyroid hormone level and thyroid color doppler ultrasound results. The thyroid status of radiation workers in different subgroups was compared. The influencing factors of Thyroid nodule were analyzed by multiple logistic regression. Results: 616 radiation workers had abnormal thyroid gland (14.3%, 616/4308) . The main manifestations of thyroid gland abnormality were abnormal Thyroid nodule (5.1%, 220/4308) and abnormal TSH level (7.1%, 308/4308) . Compared with the male radiation workers, the abnormal rate of Thyroid nodule, T3 and Tsh in female radiation workers was higher (P<0.05) , and the abnormal rate of Thyroid nodule, T3 and T4 increased with the increase of working age (P<0.05) . Radiation Workers in non-rated medical institutions and private medical institutions had the highest detection rate of Thyroid nodule (P<0.05) , and there was no significant difference in thyroid abnormalities among Workers (P<0.05) . By multiple logistic regression analysis, Sex (female) , age and institution type (private) were all independent risk factors for Thyroid nodule (95% CI: 1.548~2.763、1.002~1.030, P<0.05) . Conclusion: Ionizing radiation can cause thyroid damage in radiation workers, so we should pay more attention to the radiation protection management of female, high age, private and district medical organizations, so as to protect the health of radiation workers.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Clinical efficacy of different vascular reconstruction on adult moyamoya disease].

Objective: To investigate the clinical efficacy of superficial temporal artery -middle cerebral artery combined with encephalo-duro-arterio-myo-synangiosis (STA-MCA+EDAMS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) in the treatment of adult moyamoya disease. Methods: The clinical data of 47 adult patients with moyamoya disease who received vascular reconstruction in the Department of Neurosurgery of Taizhou Hospital of Zhejiang Province from January 2014 to January 2018 were retrospectively analyzed. Among them, 21 patients received EDAMS alone (EDAMS group, 14 patients with hemorrhagic moyamoya disease, 7 patients with ischemic moyamoya disease), 26 patients received STA-MCA combined with EDAMS (STA-MCA+EDAMS group, 17 patients with hemorrhagic moyamoya disease, 9 patients with ischemic moyamoya disease). Cerebral hemodynamics at 1 day before surgery and 3 and 6 months after surgery were compared. The clinical efficacy and postoperative complications of the two methods were compared at 3 and 6 months postoperatively in hemorrhagic and ischemic types. Results: For hemorrhagic moyamoya disease, the remission rate (94.1%) at 6 months after surgery in the STA-MCA + EDAMS group was higher than that in the EDAMS group (57.1%), and the difference was statistically significant (P<0.05). The CBF and CBV in the STA-MCA+EDAMS group were higher than those in the EDAMS group at 3 and 6 months after operation, and the MTT and TPP were lower than those in the EDAMS group, but there was no significant difference between the two groups (all P>0.05). For hemorrhagic moyamoya disease and ischemic moyamoya disease, the total incidence of postoperative complications of the two surgical methods was different, but the difference was not statistically significant (both P>0.05). Conclusion: Superficial temporal artery -middle cerebral artery combined with encephalo-duro- arterio-myo-synangiosis (STA-MCA+EDAMS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) can significantly improve neurological function and cerebral hemodynamics in adult moyamoya disease patients with high safety.

Elevated long noncoding RNA HAGLROS expression correlates with clinical progression and prognosis in osteosarcoma.

OBJECTIVE: Our study aimed to evaluate the expression pattern and prognostic value of long noncoding RNA HAGLROS (HAGLROS) in osteosarcoma. PATIENTS AND METHODS: qRT-PCR was performed to detect the expression levels of HAGLROS in osteosarcoma tissues and matched normal bone tissues. The relationship between the expression of HAGLROS and the clinicopathological features was analyzed by chi-square test. The survival curves were calculated by the Kaplan-Meier method and the difference by the log-rank test. The Cox proportional hazards model for multivariate survival analysis was used to assess predictors related to survival. RESULTS: Herein, we showed that HAGLROS was frequently upregulated in osteosarcoma tissue and cell lines compared to normal human bone tissues (p < 0.01). In addition, HAGLROS upregulation more frequently occurred in osteosarcoma specimens with advanced TNM stage (p = 0.023), positively distant metastasis (p = 0.002) and poor differentiation (p = 0.021). Survival analysis showed that osteosarcoma patients with higher HAGLROS expression suffered poorer overall survival (p = 0.012) and disease-free survival (p = 0.003). In a multivariate Cox model, it was confirmed that HAGLROS up-regulation was an independent poor prognostic factor for both 5-year overall survival (HR=3.546, 95% CI: 1.273-5.326; p = 0.002) and 5-year disease-free survival (HR=3.854, 95% CI: 1.427-5.885; p = 0.001). CONCLUSIONS: We showed that HAGLROS was an independent predictor of unfavorable prognosis in osteosarcoma patients and may serve as a potential target.

High levels of long non-coding RNA DICER1-AS1 are associated with poor clinical prognosis in patients with osteosarcoma.

OBJECTIVE: Long noncoding RNA DICER1-AS1 (DICER1-AS1) has been reported to be upregulated in osteosarcoma cells and to serve as a tumor promoter. However, the clinical significance of DICER1-AS1 in osteosarcoma remains unclear. The aim of this study was to investigate the association of DICER1-AS1 expression with prognosis of osteosarcoma. PATIENTS AND METHODS: The expression of DICER1-AS1 was measured in 214 osteosarcoma samples and normal bone samples by using Real-time PCR. The correlations between DICER1-AS1 expression and clinical features were statistically analyzed. Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier curves. Multivariate analyses were performed to analyze the prognostic significance of DICER1-AS1 expression. RESULTS: It was found that the expression levels of DICER1-AS1 in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues (p < 0.01). Higher DICER1-AS1 had significant association with clinical stage (p = 0.005) and distant metastasis (p = 0.000). Kaplan-Meier survival analysis showed that patients with high DICER1-AS1 expression had a shorter OS and DFS compared with the low DICER1-AS1 expression group (p = 0.007 and p < 0.0001). In a multivariate Cox model, our results showed that DICER1-AS1 expression was an independent poor prognostic factor for both 5-year OS (HR = 3.236, 95% CI: 1.148-5.347; p = 0.004) and 5-year DFS (HR = 3.935, 95% CI: 1.556-6.349; p = 0.001). CONCLUSIONS: DICER1-AS1 is up-regulated in osteosarcoma and may serve as a potential prognostic biomarker for osteosarcoma.

[Safety and efficacy of DCV-based DAAs therapy for chronic HCV infection in China].

Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion: DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.

Primary small cell carcinoma of the vagina with pulmonary metastasis: a case report.

Primary small cell carcinoma of the vagina is extremely rare; no standard treatment has been established despite it being highly aggressive. Here, the authors report on a 43-year-old patient who had a mass on the clitoris and no uterine or bilateral adnexal involvement. Vaginal wall biopsy revealed malignant small cell carcinoma. The carcinoma was composed of epithelial cells with round, hyperchromatic nuclei containing few distinct nucleoli, and scanty cytoplasm. Chest computerized axial tomography and pathological bronchoscopy revealed bilateral pulmonary metastases. She received radiotherapy combined with six cycles of chemotherapy (paclitaxel plus cisplatin), and achieved complete response, with complete suppression of the mass and lung metastases. There was no sign of tumor recurrence or distant metastases after 21 months of follow-up.

The curative efficacy of arthroscopic therapy in treating anterior cruciate ligament rupture with secondary osteoarthritis.

OBJECTIVE: To compare and analyze the clinical effects of arthroscopic therapy and drug therapy in treating anterior cruciate ligament (ACL) rupture with secondary osteoarthritis (OA). PATIENTS AND METHODS: A total of 68 patients that were diagnosed as ACL rupture with secondary OA in our hospital from February 2014 to February 2015 were enrolled in our study. All of the patients were randomly divided into control group (n = 30) and observation group (n = 38) according to the order of admission. The patients in the control group were given analgesic, anti-inflammatory drugs + functional rehabilitation training whereas the patients in the observation group were given ACL reconstruction + OA debridement and functional rehabilitation training under arthroscopy. RESULTS: The success rate of the observation group was 92.1%. After 3-month follow-up, the clinical total effective rate of the observation group was significantly higher than that of the control group, the prevalence of complications in the observation group was significantly lower than in the control group, and differences were statistically significant (p < 0.05). Lysholm scale scoring of observation group was significantly higher than of the control group, modified McGill pain scale score was significantly lower than that of the control group, and differences were statistically significant (p < 0.05). Quadriceps muscle peak torque, average power, and the optimal single work at 60°/s, 120°/s, and 180°/s were significantly higher than those of the control group, and differences were statistically significant (p < 0.05). CONCLUSIONS: Arthroscopic operative therapy was safe and effective for the treatment of ACL with secondary OA. Compared with drug therapy, it can significantly improve the movement function of the knee joint, so it was worthy of clinical application.

Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy.

In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

Development and validation of a chronic obstructive pulmonary disease screening questionnaire in China.

OBJECTIVE: To develop a brief, reliable screening questionnaire for chronic obstructive pulmonary disease (COPD) for use in primary care settings. METHODS: We developed a COPD Screening Questionnaire (COPD-SQ) using data collected from 19,800 subjects aged ≥40 years obtained from an epidemiological study of COPD in China in 2002 (Phase I). A stepwise logistic regression method was adopted for item reduction and scoring. We then assessed the COPD-SQ through a cross-sectional study (Phase II) among 3231 subjects aged ≥40 years. RESULTS: The final COPD-SQ consisted of seven items: age, smoking pack-years, body mass index, cough, dyspnoea, family history of respiratory diseases and exposure to biomass smoke from cooking. Using the questionnaire to screen for COPD in Phase II, we obtained high classification accuracy with an area under the curve of 0.812 (95%CI 0.786-0.838). The sensitivity, specificity and correct classification rates for COPD diagnosis were respectively 60.6%, 85.2% and 82.7% at a cut-off score of 16. CONCLUSIONS: The COPD-SQ can be used in first-level screening for COPD.

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis.

We examined the association of the interleukin-28B (IL-28B) gene rs12979860 T/C polymorphism with development of hepatitis virus-related hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library, and Chinese National Knowledge Infrastructure data bases. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) for rs12979860 and HCC/LC were calculated in a fixed-effect model (the Mantel-Haenszel method) and a random-effect model (the DerSimonian and Laird method) when appropriate. This meta-analysis included 7 eligible studies, with 1152 HCC and/or LC cases and 1326 controls. Overall, the rs12979860 T/C polymorphism was significantly associated with risk of hepatitis virus-related HCC and LC development (TT vs CC+CT, pooled OR = 1.597, 95%CI = 1.254-2.036). When they were grouped by type of hepatitis virus, similar results were found for hepatitis C virus-related groups (TT vs CC+CT, pooled OR = 1.732, 95%CI = 1.343-2.235, P value < 0.0001). In the overall analysis, the IL-28B rs12979860 T/C polymorphism was identified as a genetic risk factor for hepatitis virus-related HCC and LC development. A significant increase in the frequency of the T/T genotype was detected from chronic hepatitis to HCC and LC.

Xenogeneic islet transplantation of Ad5F35-SOCS1 infected islets for therapy of diabetes.

Islet transplantation is the most important approach for treating type I diabetes (T1DM), but the early islet apoptosis limits the therapeutic efficacy. SOCS1 (suppressor of cytokine signaling 1), not only has an effect on cytokine signaling pathway, it is also involved in the regulation of signal transduction pathway in cell apoptosis. The aim of this study was to investigate the effect of overexpression of suppressor of cytokine signaling 1 (SOCS1) in islet grafts. In this paper, the Ad5F35-SOCS1 infected islets were constructed, meanwhile the diabetic mice were established and the xenogenic islet transplantation was performed. After islet transplantation, the blood glucose levels of islet recipients were monitored and the kidney samples were harvested to perform the histological and apoptosis assay. The results showed that the blood glucose was restored in most of the diabetic mice after Ad5F35-SOCS1 infected islets transplantation, and normoglycaemia was maintained for a long time. Furthermore, histological analysis indicated that the infected grafts with overexpression of SOCS1 showed strong insulin secretion function and decreased apoptosis in the early post-transplant period. These results demonstrate that SOCS1 could be the underlying target molecule in islet therapy which has great clinical and practical significance.

Suppressor of cytokine signaling 1 inhibits apoptosis of islet grafts through caspase 3 and apoptosis-inducing factor pathways in rats.

A significant portion of pancreatic islet grafts can be destroyed by apoptosis, failing to engraft in the early period after transplantation. Recently, we observed that overexpression of suppressor of cytokine signaling 1 (SOCS1) in islet grafts achieved an antiapoptotic effect, prolonging graft survival in a rat transplant model. Caspase 3 is the central executioner caspase that is activated by upstream cascades in a caspase-dependent apoptosis pathway. Apoptosis inducing factor (AIF) is a key protein that can be released from mitochondria, translocating to the nucleus in the caspase-independent apoptosis pathway. In this study, we investigated whether these two pathways were involved in cytoprotection afforded by SOCS1 on islet grafts. We used a chimeric adenovirus vector (Ad5F35-SOCS1) to enhance SOCS1 expression in isolated Sprague-Dawley rat islets, which were transplanted into recipients experiencing streptozotocin-induced diabetes. We analyzed the expressions of active (cleaved) caspase 3 and AIF on islets. The Ad5F35-SOCS1-infected islets with higher SOCS1 expression showed decreased levels of active caspase 3 and intranuclear AIF after treatment with tumor necrosis factor-α and cycloheximide in vitro. The diabetic recipients transplanted with Ad5F35-SOCS1-infected islets showed longer periods of normoglycemia versus recipients transplanted with mock-infected islets (P < .05) due to prolonged graft survival. A histological analysis indicated that the Ad5F35-SOCS1-infected islet grafts displayed decreased caspase 3 activation and AIF translocation (to nucleus) in the early posttransplant period. These results demonstrated that the expression of SOCS1 in islet grafts protected them from apoptosis through caspase 3 dependent and AIF caspase-independent-pathways.

Impedance labelless detection-based polypyrrole protein biosensor.

A simple and sensitive electrochemical immunosensor with impedance labelless detection and novel data processing method was investigated. One-step copolymerization was used to electrochemically deposit an antibody impregnated polypyrrole film on a glassy carbon electrode surface for the immunosensor. Impedance measurements provided a labelless or reporterless method to detect antibody (Ab)-antigen (Ag) interactions. Dimensionless analysis was employed to successfully process the measured impedance data. Since the method derived unit impedance change to eliminate or reduce the variation of the bulk electronic properties of Ab/polypyrrole films, the signal to noise ratio (S/N) was significantly improved for high sensitivity and specificity. Nonspecific binding effect was studied by array electrode chips and was found out that the polypyrrole electrode without antibody attachment had much stronger nonspecific binding effect than the Ab/polypyrrole electrode; incubation followed by thoroughly washing significantly reduced the nonspecific interference. 10 pg/ml detection limit and superior specificity were achieved by the method, demonstrating a highly sensitive labelless immunosensor in comparison with the detection limit of ng -microgram/ml for the reported polypyrrole based immunosensors. The electrochemical immunosensors presented in this paper, due to its simplicity, low cost, high sensitivity and superior specificity, could be an invaluable tool for clinical diagnostics and could have potential applications in drug discovery, environmental and food analysis.