[Transscleral ciliary surgery in glaucoma:from destructive surgery to minimally invasive surgery].

Over the years, there has been significant advancement in the safety and effectiveness of external cyclosurgery for glaucoma. This progress ranges from the initial "cyclodestructive surgery" to modern cycloplasty techniques, expanding beyond end-stage glaucoma treatment. Notably, innovative approaches like micropulse transscleral cycloplasty and ultrasonic cycloplasty are now being employed in earlier stages of glaucoma with better visual acuity, qualifying as minimally invasive procedures. Through a comprehensive review of the historical evolution of external cyclosurgery, elucidation of the mechanisms, clinical outcomes, and potential complications associated with novel cycloplasty techniques, and integration of practical clinical insights, this article aims to furnish clinicians with a profound comprehension of external cyclosurgery for glaucoma.

[The relationship between differentially expressed thyroid cancer genes and clinical characteristics in metastatic children and adolescents].

Objective: To investigate the relationship between genes and clinical characteristics in children and adolescents with metastatic differentiated thyroid cancer (caDTC). Methods: A cross sectional study. A total of 67 caDTC patients with lymph node metastasis or distant metastasis in Peking Union Medical College Hospital from December 2020 to December 2022 were included, according to the inclusion and exclusion criteria. Then the differences in clinicopathologic features and iodine intake were compared among different genomes, and the age subgroups divided by the age of 12 were further analyzed. Results: Among the 67 cases of caDTC, the diagnosed age [M(Q1, Q3)]was 13.2 (9.7, 16.9) years old, with 23 males and 44 females. There were 68.7% (46/67) of patients have distant metastasis (M1 stage). Pathogenic or potentially pathogenic gene variants were detected in 68.7% (46/67) of the patients, with RET or NTRK fusion (RET/NTRK) being the most common [43.3%(29/67)], BRAF V600E mutation followed [19.4%(13/67)].There was only 1 caDTC with NRAS Q61R mutation. The patients were divided into RET/NTRK fusion group (n=29), BRAF mutation group (n=12), other mutation group (n=4), and non-mutation group (n=21) (1 patient was not included in the gene mutation subgroup comparison due to the presence of NRAS Q61R mutation and BRAF V600E mutation). The comparison of gene feature groups showed that compared to the BRAF mutation group, caDTC with RET/NTRK fusion tended to have a lower age at diagnosis [12.6(9.3, 15.9) vs 17.2(15.5, 18.1) years old, P<0.001], the proportion of mutation load≥2 was higher (10.4% vs 8.3%, P=0.027), with statistically significant difference. Among 46 M1 stage patients, 71.7% (33/46) had initial iodine intake, and 30.4% (14/46) developed radioiodine-refractory (RAIR). In age group comparison, the<12 year old group had a higher proportion of male patients (51.9% vs 22.5%, P=0.013) and a lower incidence of BRAF V600E mutations (0 vs 32.5%, P<0.001) compared to the≥12 year old group, and the differences were statistically significant. Conclusions: The incidence of RET/NTRK fusion ranks first in metastatic caDTC, featured with younger age at diagnosis and higher rate of distant metastasis. Although most metastatic lesions initially consume iodine, they are prone to RAIR. Attention should be paid to the potential role of RET/NTRK fusion in the invasion and iodine resistance of young caDTC patients.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

[Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].

Temozolomide resistance is a major cause of recurrence and poor prognosis in neuroglioma. Recently, growing evidence has suggested that mitophagy is involved in drug resistance in various tumor types. However, the role and molecular mechanisms of mitophagy in temozolomide resistance in glioma remain unclear. In this study, mitophagy levels in temozolomide-resistant and -sensitive cell lines were evaluated. The mechanisms underlying the regulation of mitophagy were explored through RNA sequencing, and the roles of differentially expressed genes in mitophagy and temozolomide resistance were investigated. We found that mitophagy promotes temozolomide resistance in glioma. Specifically, small ubiquitin-like modifier specific protease 6 (SENP6) promoted temozolomide resistance in glioma by inducing mitophagy. Protein-protein interactions between SENP6 and the mitophagy executive protein PTEN-induced kinase 1 (PINK1) resulted in a reduction in small ubiquitin-like modifier 2 (SUMO2)ylation of PINK1, thereby enhancing mitophagy. Our study demonstrates that by inducing mitophagy, the interaction of SENP6 with PINK1 promotes temozolomide resistance in glioblastoma. Therefore, targeting SENP6 or directly regulating mitophagy could be a potential and novel therapeutic target for reversing temozolomide resistance in glioma.

[Prickle planar cell polarity protein 1 involved in the pathogenesis of skeletal class â ¢ malocclusion].

Objective: To explore the mechanisms of prickle planar cell polarity protein 1 (PRICKLE1) involved in the occurrence of skeletal Class Ⅲ malocclusion. Methods: After extracting the genomic DNA of all family members of the skeletal Class Ⅲ malocclusion pedigree with maxillary hypoplasia collected in the Department of Orthodontics at the Affiliated Stomatological Hospital of Nanjing Medical University in October 2021, whole exome sequencing and Sanger sequencing were performed to screen pathogenic genes/mutation sites and validate the mutations. Jaw tissue was collected during the operation of orthognathic patients who were treated in the Department of Oral and Maxillofacial Surgery at the same hospital from October 2021 to December 2022. Following the extraction of human jaw bone marrow mesenchymal stem cells and transfection with overexpressing lentivirus (lentiviruses overexpressing the gene of interest served as the wild group, lentiviruses overexpressing mutation site served as the mutant group) and knockdown lentivirus (divided into knockdown group 1 and 2, with transfection interference negative lentiviruses as the control group). Various assays including real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, proliferation and Transwell assays, alkaline phosphatase staining and alizarin red staining were performed. Construction of zebrafish animal model, morpholino oligonucleotide (MO) were injected to knock down the expression of prickle1a and prickle1b in zebrafish (co-knocking group), and the control group was injected with standardized MO as a reference. Transcriptome sequencing, enrichment analysis and co-expression analysis were performed on the zebrafish craniofacial tissues of the two groups. Results: Two patients of this family carried this mutation PRICKLE1 c.113C>T. The transfection experiments showed that compared with the wild group (relative expression of PRICKLE1 was 21.97±0.60), the relative expression of mutant group (5.05±0.05) was significantly reduced (P<0.05), and cell proliferation and migration ability significantly enhanced (P<0.05), and osteogenic differentiation ability was significantly reduced (P<0.05). Compared with the control group, the proliferation and migration ability of cells in the two knockdown groups were significantly enhanced (P<0.05), and the osteogenic differentiation ability was significantly reduced (P<0.05). Zebrafish model experiments showed the width of the ethmoid plate was significantly reduced in the co-knocking group (282.50±61.77, t=5.29, P<0.001) compared with the control group (338.80±24.92). Transcriptome data and enrichment analysis showed that the differentially expressed genes were significantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathway after the simultaneous knockdown of prickle1a and prickle1b in zebrafish. Conclusions: PRICKLE1 c.113C>T mutation might suppress the osteoblastic differentiation ability of jaw bone marrow mesenchymal stem cells by downregulating the MAPK signaling pathway, thereby involving the development of skeletal Class Ⅲ malocclusion.

[Percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of spinal metastases].

OBJECTIVE: To investigate the effectiveness of percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of patients with spinal metastases. METHODS: In the study, 12 patients of spinal metastases treated with percutaneous pedicle screw fixation combined expandable tubular retractor in our hospital were retrospectively reviewed between June 2017 and October 2019. Among the 12 patients, 9 were males and 3 were females; the median age was 62.5 years [(65.1±2.9) years]. The decompression segment of 7 patients was located at the lower thoracic spine (including 1 patient with incomplete paraplegia) and the decompression segment of 5 patients was located at the lumbar spine; Tomita score was 6.0±0.6. Perioperative data of the patients were reviewed. Visual analog scale (VAS score), Karnofsky score, and Eastern Cooperative Oncology Group (ECOG) score were compared before and after surgery. The patient's survival, adjuvant treatment, and internal fixation failure were observed in the follow-up period. RESULTS: All the 12 patients had a successful operation with percuta-neous pedicle screw fixation combined expandable tubular retractor. The average operative time, blood loss, and blood transfused of the patients were (247.0±14.6) min, (804.2±222.3) mL and (500.0±100.0) mL, respectively. The average amount of drainage was (240.8±79.3) mL. Drainage tubes were pulled out early postoperative [(3.2±0.3) d], allowing early mobilization. The patients discharged (7.8±0.8) d postoperative. All the patients were followed up for 6-30 months, and the average overall survival time was (13.6±2.4) months. During the follow-up period, 2 patients experienced screw displacement, the internal fixation was stable after conservative treatment and no revision surgery was performed. The VAS of the patients was 7.1±0.2 before surgery, which decreased to 2.3±0.1 and 2.8±0.4 at 3 and 6 months after surgery (P < 0.05). The Karnofsky score of the patients was 59.2±1.9 before surgery, which increased to 75.0±1.9 and 74.2±3.1 at 3 and 6 months after surgery (P < 0.05). The ECOG of the patients was 2.3±0.2 before surgery, which decreased to 1.7±0.1 and 1.7±0.2 at 3 and 6 months after surgery (P < 0.05). CONCLUSION: For selected patients with spinal metastases, minimally invasive surgical treatment of spinal metastases (percutaneous pedicle screw internal fixation combined with expandable tubular retractor) can effectively relieve the clinical symptoms and improve the quality of life, with satisfactory clinical outcome.

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

[Characteristics of alveolar bone loss in severe periodontitis and consideration of rehabilitation with implant].

Severe periodontitis is the main cause of tooth loss in adults, with varying degrees of horizontal and vertical alveolar bone loss. In view of the complex alveolar bone defect, a suitable surgery planning should be made on the basis of fully nuderstanding the characteristics of alveolar bone defect in severe periodontitis and the key points of bone augmentation technique, so as to choose an appropriate method for reconstruction of alveolar bone and complete the implantation and restoration to ensure the integrity of dentition, which are important for the long-term stability of periodontal health. Based on clinical experiences and literature review, we summarizes the characteristics of alveolar bone loss in patients with severe periodontitis and the timing of implant placement after bone augmentation surgery, in order to provide reference for implant treatment of severe periodontitis.

[Effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma].

Objective: To investigate the effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma. Methods: This retrospective cohort study included 97 patients who underwent laparoscopic low anterior resection of rectal adenocarcinoma in General Surgery Department, the First Affiliated Hospital of Soochow University from January 2017 to June 2021. According to the implementation of pelvic peritoneum reconstruction, the subjects were divided into study group (48 patients underwent pelvic peritoneum reconstruction after laparoscopic resection) and control group (49 patients not underwent pelvic peritoneum reconstruction). The two groups were compared in terms of Wexner score of anal function, anorectal manometry results, normal rate of defecation sensation, pelvic floor anatomical structure and postoperative complications. Five-year survival analysis was performed. Results: Patients in the study group and the control group were (61.25±10.38) years old and (59.47±11.40) years old (P>0.05). The proportions of male patients were 60.4% (29 cases) and 55.1% (27 cases) (P>0.05) in the study group and control group, respectively. At 3, 6 and 12 months after surgery, Wexner scores of anal function in the study group were lower than those in the control group [(14.29±2.07) vs (16.33±2.18), P<0.001; (9.57±2.34) vs (11.26±2.85), P=0.002; (5.41±1.36) vs (7.86±1.95), P<0.001, respectively]. The anal resting pressure and anal systolic pressure of the study group were higher than those of the control group [(56.29±7.31) mmHg vs (52.88±6.65) mmHg, P=0.018; (129.33±17.36) mmHg vs (110.45±15.22) mmHg, P<0.001, respectively] (1 mmHg=0.133 kPa). The rectal sensory volume, rectal maximum tolerance volume, and the length of anal high-pressure area in the study group were greater than those in the control group [(32.15±4.38) vs (29.76±4.29), P=0.008; (209.57±40.27) vs (184.39±37.56), P=0.002; (3.07±0.52) vs (2.80±0.49), P=0.010, respectively]. At 3 and 6 months after surgery, the normal rates of defecation sensation in the study group were 47.9% (23 cases) and 70.8% (34 cases), respectively, higher than those in the control group [26.5% (13 cases) and 51.0% (25 cases)] (P=0.029 and 0.046, respectively). The detection rate of intestinal tube accumulation in the study group was lower than that in the control group [12.5% (6 cases) vs 38.9% (19 cases)] (P=0.003). There was no significant difference in the total incidence of complications (anastomotic leakage, abdominal infection, intestinal obstruction, pendant pneumonia and urinary tract infection) between the two groups [18.8% (9 cases) vs 24.5% (12 cases)] (P=0.493). There was no significant difference in 5-year cumulative survival rate between the study group and the control group (71.6% vs 68.2%, P=0.309). Conclusion: Pelvic peritoneum reconstruction can improve postoperative anal function and reduce intestinal tube accumulation in patients underwent laparoscopic low anterior resection of rectal adenocarcinoma with high safety and feasibility.

Bevacizumab biosimilar candidate TAB008 compared to Avastin® in patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter study.

BACKGROUND: Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC). METHOD: In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics. RESULTS: A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin®, and the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin®, which became negative upon follow-up. The steady-state trough concentrations (Cssmin) were 106.13 µg/mL in TAB008 group and 96.03 µg/mL in Avastin® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 101.74-120.05%). CONCLUSIONS: TAB008 is similar to Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov number; NCT05427305.

[Linagliptin improves diabetic kidney disease in rats by promoting mitochondrial biogenesis through the AMPK/PGC-1α/TFAM pathway].

OBJECTIVE: To investigate whether linagliptin improves diabetic kidney disease (DKD) by promoting mitochondrial biosynthesis via activating adenosine monophosphate activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α/mitochondrial transcription factor A (AMPK/PGC-1α/TFAM) pathway. METHODS: With 6 male SD rats feeding normal chow as the control group, 16 SD rat models of DKD induced by intraperitoneal injection of 45 mg/kg STZ and high-fat and high-glucose feeding for 4 weeks were randomized into DKD model group and linagliptin treatment group. The rats in the latter two groups were subjected to daily intragastric administration of vehicle or 5 mg/kg linagliptin (dissolved in 5 g/L sodium carboxymethylcellulose, final concentration of 2 mg/mL) for 12 weeks with further high-fat and high-glucose feeding. After the treatments, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected for testing blood glucose, liver function and lipid metabolism; HE, PAS, Masson, Sirius red staining and electron microscopy were used to observe renal tissue damage. Renal expressions of transforming growth factor ß1 (TGF-ß1), fibronectin (FN) and collagen I (Col I) were detected by immunohistochemistry, and the changes in membrane potential (ΔψM) and ATP enzyme content were analyzed to assess mitochondrial damage; The expressions of AMPK/PGC-1α/TFAM pathway proteins were detected using Western blotting. RESULTS: Compared with DKD model rats, the rats receiving linagliptin treatment showed significantly decreased blood glucose level (P < 0.01) and improved proteinuria (P < 0.05) with obviously alleviated renal ultrastructural damage and fibrosis, increased ATPase content and ΔψM (P < 0.0001), and enhanced renal expressions of P-AMPK/AMPK, PGC-1α and TFAM (P < 0.05). CONCLUSIONS: Linagliptin improves proteinuria and renal fibrosis in rat models of DKD possibly by activating the AMPK/PGC-1α/TFAM pathway to promote mitochondrial biosynthesis.

[Related factors of urinary tract infections in inpatients based on real world data].

To analyze the risk factors for urinary tract infection (UTI) among inpatients. The case data of 1 875 inpatients receiving urinary bacterial culture in Beijing Haidian Hospital from October 2019 to May 2021 were analyzed retrospectively. According to the etiological diagnostic criteria of UTI, they were divided into infection group and non-infection group. The species and distribution of pathogens in the infection group were analyzed, and the case data and laboratory indexes were subjected to univariate analysis. The variables with statistical significance were selected for binary logistic regression to analyze the risk factors of urinary tract infection and establish a prediction model. The receiver operating characteristic (ROC) curve was drawn for each parameter included in the model, and the area under the curve (AUC) was calculated. The diagnostic and predictive efficacy of each parameter alone and their combination for UTI were evaluated. So, a total of 1 162 patients with non-infection group and 713 patients with UTI were detected. Among the cultured pathogens, the constituent ratio of Gram-negative bacteria, Gram-positive bacteria and fungi was 57.2%(408/713), 35.9%(256/713) and 6.9%(49/713) respectively. Multivariate analysis showed that, Age, duration of urinary catheterization>7 d, stroke and orthopedic surgery were the risk factors of UTI among inpatients. The use of antibiotics is a protective factor for urinary tract infections. The prediction model of UTI was established by the risk factors, age, duration of urinary catheterization>7 d, stroke, orthopedic surgery, urinary leukocyte esterase, urinary nitrite and Coefficient of variability of red blood cell volume distribution width (RDW-CV). The AUC of the combination of the eight parameters in diagnosing and predicting UTI was 0.835 (95%CI: 0.816-0.855), with the sensitivity of 70.7% and the specificity of 82.8%. In conclusion,the combination of the eight parameters can better assist in the diagnosis and prediction of UTI, and provide an experimental basis for clinicians to judge UTI.

[Interference of CTPS gene promotes toosendanin-induced apoptosis of human gastric cancer MKN-45 cells].

OBJECTIVE: To investigate the effect of interference of CTPS gene on toosendanin-induced apoptosis of gastric cancer MKN-45 cells. METHODS: Bioinformatic analysis was used to analyze CTPS gene expression in human gastric cancer tissues and the overall survival of gastric cancer patients with high CTPS gene expression. Human gastric cancer MKN-45 cells were transfected with a short hairpin interfering RNA targeting CTPS gene, and 48 h later, qRT-PCR and Western blotting were used to detect cellular expression CTPS at both the mRNA and protein levels. MKN-45 cells with CTPS knockdown were treated with 80 nmol/L toosendanin for 48 h, and the cell viability was assessed with MTT assay; the cell morphology was observed using laser confocal microscope, and the expression of γH2AX was detected with immunofluorescence assay. RESULTS: Bioinformatic analysis suggested that CTPS was highly expressed in human gastric cancer tissues, and gastric cancer patients with high CTPS gene expression had a shorter overall survival. MKN-45 cells transfected with Sh-CTPS interference vector showed significantly lowered cell survival rate (P < 0.01) with obvious cell shrinkage, irregular morphology, typical apoptotic changes, and increased cell apoptosis rate (P < 0.05). Treatment of the transfected cells with 80 nmol/L toosendanin for 48 h resulted in further reduction of the cell survival rate (P < 0.001), and the cells showed an increased apoptotic rate (P < 0.05) with appearance of apoptotic bodies. CONCLUSION: Interference of CTPS gene can promote TSN-induced apoptosis of gastric cancer MKN-45 cells.

Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial.

BACKGROUND: Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events. METHODS: In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms. RESULTS: General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [- 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy. CONCLUSIONS: This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events. TRIAL REGISTRATION: Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).

[Comparison of application effects of colonoscopy, fecal immunochemical test and a novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population].

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.

Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model.

OBJECTIVES: To advance the initiative of ending the global epidemic, long-lasting HIV protection is needed through sustained release of antiretroviral drugs for months to years. We investigated in macaques the safety and efficacy of biodegradable polycaprolactone implants releasing tenofovir alafenamide for HIV pre-exposure prophylaxis (PrEP). METHODS: Implants were administered subcutaneously in the arm using a contraceptive trocar. Efficacy against vaginal simian-HIV (SHIV) infection was investigated in six pigtailed macaques that received two tenofovir alafenamide implants (0.35 mg/day), one in each arm, for a total release rate of tenofovir alafenamide at 0.7 mg/day. Macaques were exposed to SHIV twice weekly for 6 weeks. Statistical analyses were used to compare outcome with eight untreated controls. Histological assessments were performed on skin biopsies collected near implantation sites. RESULTS: Median (range) tenofovir diphosphate level in PBMCs was 1519 (1068-1898) fmol/106 cells. All macaques with tenofovir alafenamide implants were protected against vaginal SHIV infection. In contrast, 7/8 controls were infected after a median of 4 SHIV exposures (P = 0.0047). Histological assessment of tissues near tenofovir alafenamide implant sites showed inflammation and necrosis in 5/6 animals, which were not evident by visual inspection. CONCLUSIONS: We demonstrated complete protection against vaginal SHIV infection with two implants releasing a total of 0.7 mg of tenofovir alafenamide per day. We also identified tenofovir diphosphate concentrations in PBMCs associated with complete vaginal protection. Consistent with previous findings, we observed adverse local toxicity and necrosis near the tenofovir alafenamide implant site. Improved tenofovir alafenamide implants that are safe and maintain high efficacy have the potential to provide long-lasting protection against vaginal HIV infection.