Evidence for causal effects of neuropsychiatric conditions on risk of venous thromboembolism: A univariable and multivariable Mendelian randomization study.

BACKGROUND: Substantial observational evidence suggests an association between neuropsychiatric conditions and venous thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the bidirectional causal effects between four neuropsychiatric conditions and VTE, deep vein thrombosis, and pulmonary embolism (PE). METHODS: Genetic variants associated with four neuropsychiatric conditions (ie, schizophrenia, major depressive disorder [MDD], bipolar disorder, and epilepsy) and VTE, deep vein thrombosis, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate the causal relationships among these conditions. The primary causal estimates were obtained using the inverse variance weighted method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using the MR pleiotropy residual sum, funnel plots, and outlier (MR pleiotropy and residual sum and outlier) method. RESULTS: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46; P = .004; PE: OR, 1.36; 95% CI, 1.09-1.69; P = .006) and that PE has an adverse causal effect on MDD (OR, 1.02; 95% CI, 1.00-1.04; P = .026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE. CONCLUSIONS: Our results suggest that genetic susceptibility to MDD might have an adverse causal effect on the risk of VTE and PE and that PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Sleeve gastrectomy links the attenuation of diabetic kidney disease to the inhibition of renal tubular ferroptosis through down-regulating TGF-ß1/Smad3 signaling pathway.

PURPOSE: To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD). METHODS: DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms. RESULTS: SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-ß1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-ß1/Smad3 signaling pathway. Inhibition of TGF-ß1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-ß1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-ß1 concentrations, and down-regulated the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-ß1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.

Two-Stage Treatment Protocol of Fungal Periprosthetic Hip and Knee Joint Infections: the Clinical Experience from a Single Center Experience.

PURPOSE OF THE STUDY: To evaluate the clinical results and safety of fungal periprosthetic joint Infections (fPJIs) using two-stage treatment protocol. MATERIAL AND METHODS: 8 patients with fPJIs (3 hips and 5 knees) using two-stage revision were reviewed retrospectively and followed up at least 2 years. The preoperative demographic data, two-stage treatment protocol, results of microbiology and histologic workup and postoperative follow-up results (reimplantation success rate and infection free time) were recorded. RESULTS: 7 patients got successful reimplantation, with a 75% reimplantation success rate. Two patients got knee arthrodesis eventually. All patients were infection free with a median follow-up of 4.0 ± 2.0 years (range, 2-7 years). Of them, Candida species were found in 7 patients, while non-Candida specimen was only isolated in 1 patient with Aspergillus. Only 2 patients had coexisting bacterial infection (Methicillin-resistant coagulase-negative Staphylococci and Proteus mirabilis respectively). The average interval between the initial surgery and diagnosis of fPJIs was 21.50±34.79 months (range, 4-104 months). The mean time of spacer implantation was 7.75±2.77 months (range, 6-14 months). None serious complication or above knee amputation was found. DISCUSSION: fPJIs are very rare and considerable challenge after total hip or knee arthroplasty. The goal of therapy is to eradicate local infection and maintain function. Candida species were the most common pathogen. The duration between spacer placement and staged reimplantation was highly variable, and generally dependent upon the results of joint aspirates and infl ammatory markers. The current study shows that the two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. CONCLUSIONS: The two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. The safety and effi cacy of biantibiotical impregnated (antifungal + antibiotics) cement spacer is confi rmed. Further evidence-based work is needed to determine the optimal drug dose and reimplantation time. KEY WORDS: two-stage treatment protocol, fungal periprosthetic infections, hip spacer, knee spacer.

[Exosomes from ectoderm mesenchymal stem cells inhibits lipopolysaccharide-induced microglial M1 polarization and promotes survival of H2O2-exposed PC12 cells by suppressing inflammatory response and oxidative stress].

OBJECTIVE: To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells (EMSCs-exo) for repairing secondary spinal cord injury. METHODS: EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa, identified by transmission electron microscope, nanoparticle tracking analysis (NTA), and Western blotting, and quantified using the BCA method. Neonatal rat microglia purified by differential attachment were induced with 100 µg/L lipopolysaccharide (LPS) and treated with 37.5 or 75 mg/L EMSCs-exo. PC12 cells were exposed to 400 µmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L. The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT- PCR, and the concentrations of IL- 6, IL-10, and IGF-1 in the supernatants were measured with ELISA. The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry. RESULTS: The isolated rat EMSCs showed high expressions of nestin, CD44, CD105, and vimentin. The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63, CD81, and TSG101 but not vimentin. In LPS-treated microglia, EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression (P < 0.05). EMSCs-exo treatment at 75 mg/L, as compared with the lower concentration at 37.5 mg/L, more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia, and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells (P < 0.05). CONCLUSION: EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival, suggesting its potential in controlling secondary spinal cord injury.

Testosterone promotes the migration, invasion and EMT process of papillary thyroid carcinoma by up-regulating Tnnt1.

PURPOSE: To explore the key genes and molecular pathways in the progression of thyroid papillary carcinoma (PTC) promoted by testosterone using RNA-sequencing technology, and to provide new drug targets for improving the therapeutic effect of PTC. METHODS: Orchiectomy (ORX) was carried out to construct ORX mouse models. TPC-1 cells were subcutaneously injected for PTC formation in mice, and the tumor tissues were collected for RNA-seq. The key genes were screened by bioinformatics technology. Tnnt1 expression in PTC cells was knocked down or overexpressed by transfection. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay and transwell assay were adopted, respectively, for the detection of cell proliferation, colony formation, migration and invasion. Besides, quantification real-time polymerase chain reaction (qRT-PCR) and western blot were utilized to determine the mRNA and protein expression levels of genes in tissues or cells. RESULTS: Both estradiol and testosterone promoted the growth of PTC xenografts. The key gene Tnnt1 was screened and obtained by bioinformatics technology. Functional analysis revealed that overexpression of Tnnt1 could markedly promote the proliferation, colony formation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) process of PTC cells, as well as could activate p38/JNK pathway. In addition, si-Tnt1 was able to inhibit the cancer-promoting effect of testosterone. CONCLUSION: Based on the outcomes of bioinformatics and basic experiments, it is found that testosterone can promote malignant behaviors such as growth, migration, invasion and EMT process of PTC by up-regulating Tnnt1 expression. In addition, the function of testosterone may be achieved by activating p38/JNK signaling pathway.

[Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors].

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

[Shenqi Wenfei Formula alleviates chronic obstructive pulmonary disease in rats with pulmonary qi deficiency syndrome by regulating NLRP3/GSDMD pyroptosis pathway].

OBJECTIVE: To investigate the effects of Shenqi Wenfei (SQWF) Formula on the NLRP3/GSDMD signaling pathway in pulmonary qi deficiency syndrome rats with chronic obstructive pulmonary diseases (COPD). METHODS: Rat models of COPD and lung qi deficiency syndrome induced by exposure to cigarette smoke and lipopolysaccharide (LPS) injection were randomized (n=8) for treatment with low-, medium- and high-dose SQWF or Yu Ping Feng (YPF). The changes in body weight, grip strength, lung function, pulmonary pathology, peripheral blood inflammatory cell counts, and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were examined. The expressions of proteins associated with the NLRP3/GSDMD signaling pathway in the lung tissues were determined with RT-qPCR and immunohistochemistry. RESULTS: The rat models of COPD and lung qi deficiency syndrome showed significantly reduced body weight, grip strength and lung function (P<0.01) with severe lung pathologies, increased levels of WBC, NEU% and MON% (P<0.01), decreased LYM% (P<0.01), and increased levels of TNF-α, IL-6, IL-1ß and IL-18 in the BALF (P<0.01); the mRNA and protein expression levels of NLRP3, ASC, GSDMD and IL-1ß all increased significantly in the lung tissue (P<0.01). Treatment with SQWF and YPF obviously increased body weight and improved grip strength, pulmonary function and lung pathology of the COPD rats (P<0.05). The treatments obviously improved the changes in peripheral blood inflammatory cell counts and inflammatory factors in the BALF of the rat models (P<0.01) and lowered the expressions of NLRP3, ASC, GSDMD and IL-1ß in the lung tissues (P<0.05) without significantly affecting the mRNA levels of caspase-1 and IL-18 (P>0.05), and the effects of SQWF were dose-dependent. CONCLUSION: SQWF Formula relieves inflammatory response and injury in the lung tissue of COPD rats with pulmonary qi deficiency syndrome possibly by inhibiting pyroptosis through regulating the NLRP3/GSDMD pathway.

[Clinicopathological analysis of benign mammary ductal cystic papillomatosis with loss of myoepithelial cells].

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.

[The application value of shear wave dispersion and shear wave elastography combined with serological indicators in the evaluation of liver fibrosis].

Objective: To explore the application value of shear wave dispersion (SWD) and shear wave elastography (SWE) combined with serological indicators in the evaluation of liver fibrosis. Methods: A total of 219 patients with liver disorders who underwent liver biopsy were prospectively collected in Huashan Hospital, Fudan University from January 2021 to September 2022, including 130 males and 89 females, aged from 18 to 76 (42±12) years. All patients underwent SWD and SWE examinations before liver biopsy. Serological indicators including alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP)) and γ-glutamyl transpeptadase (GGT) were also collected. Based on pathological diagnosis of liver fibrosis stage (from S0 to S4), the distribution of dispersion slope and liver elastic modulus at different fibrosis stages were analyzed in all patients. All patients were divided 7: 3 into training set (156 cases) and validation set (63 cases) in chronological order. In training set, factors influencing liver fibrosis≥S2 stage and S4 stage were analysed using binary logistic regression. The predictive models were established for diagnosing liver fibrosis≥S2 stage and S4 stage by using R language, and the models were evaluated by the area under curve (AUC) and calibrated for validation. Results: The dispersion slope and elastic modulus increased with the severity of fibrosis, with statistically significant differences in different fibrosis stages (both P<0.001). In training set, dispersion slope, elastic modulus, ALT, AST, and GGT were influential factors in liver fibrosis≥S2 stage and S4 stage(both P<0.05), and prediction models were constructed based on these indicators. In training set, the AUCs of the predictive model, SWD and SWE for diagnosingliver fibrosis≥S2 stage were 0.743 (95%CI: 0.665-0.821), 0.709 (95%CI: 0.628-0.790) and 0.725 (95%CI: 0.647-0.804), respectively; for diagnosing liver fibrosis S4 stage, the AUCs were 0.988 (95%CI: 0.968-1.000), 0.908 (95%CI: 0.852-0.963) and 0.974 (95%CI: 0.945-1.000), respectively. In validation set, the AUC of the predictive model, SWD and SWE for diagnosing liver fibrosis≥S2 stage were 08.735 (95%CI: 0.612-0.859), 0.658 (95%CI:0.522-0.793) and 0.699 (95%CI:0.570-0.828), respectively; for diagnosing liver fibrosis S4 stage, the AUC were 0.976 (95%CI: 0.937-1.000), 0.872 (95%CI: 0.757-0.988) and 0.948 (95%CI: 0.889-1.000), respectively. The calibration curves of the prediction models were consistent in the training and validation sets. Conclusion: The predictive model of SWD and SWE combined with serological indicators is helpful in the diagnosis of stage of liver fibrosis non-invasively.

[Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy].

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Diagnostic performance of diffusion-weighted imaging and intravoxel incoherent motion for renal lesions: a meta-analysis.

AIM: To compare the diagnostic performance of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) parameters, specifically true diffusion coefficient (D), pseudo diffusion coefficient (D∗), and perfusion fraction (f) for quantitatively differentiating benign and malignant renal lesions. MATERIALS AND METHODS: A comprehensive search was conducted in the EMBASE and PubMed databases before September 2022 to identify studies in English investigating the diagnostic accuracy of DWI and IVIM in renal lesions. The quality of the included studies was assessed using the QUADAS-2 tool. Pooled sensitivity, specificity, and area under the curve (AUC) values were estimated for each parameter. RESULTS: A total of 19 studies involving 1,860 renal lesions (1,160 malignant and 700 benign), met the inclusion criteria. Among these studies, 15 assessed the apparent diffusion coefficient (ADC), four assessed IVIM, and three evaluated both ADC and IVIM. The pooled sensitivity, specificity, and AUC for ADC were 0.84 (95% confidence interval [Cl], 0.79-0.88), 0.82 (95% Cl, 0.72-0.89), and 0.89 (95% Cl, 0.86-0.92), respectively. The IVIM parameter with the highest diagnostic accuracy was D, with a pooled sensitivity, specificity, and AUC of 0.89 (95% Cl, 0.74-0.96), 0.96 (95% Cl, 0.85-0.99), and 0.98 (95% Cl, 0.96-0.99), respectively. The pooled sensitivity, specificity and AUC for f were 0.67 (95% Cl, 0.55-0.77), 0.81 (95% Cl, 0.30-0.98), and 0.73 (95% Cl, 0.69-0.77), respectively. The pooled sensitivity, specificity, and AUC for D∗ were 0.87 (95% Cl, 0.81-0.91), 0.59 (95% Cl, 0.48-0.70), and 0.82 (95% Cl, 0.78-0.85), respectively. CONCLUSION: This meta-analysis indicated that both IVIM and DWI had moderate to high diagnostic accuracy for differentiating benign and malignant renal lesions. Among the IVIM parameter, D exhibited the highest diagnostic accuracy, demonstrating higher sensitivity and specificity than ADC, D∗, and f.

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer.

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.

Association of Computed Tomography Radiomics Signature with Progression-free Survival in Neuroblastoma Patients.

AIMS: To investigate the association of computed tomography radiomics signature with progression-free survival (PFS) in neuroblastoma patients. MATERIALS AND METHODS: We retrospectively included 167 neuroblastoma patients who were divided into a training set and a test set through stratified sampling at a ratio of 7:3. Regions of interest of the primary tumours were delineated on pretreatment contrast-enhanced computed tomography images and radiomics features were extracted from them. The intraclass correlation coefficient, Pearson correlation coefficient, and least absolute shrinkage and selection operator Cox regression algorithm were applied to select radiomics features and construct the radiomics signature. The effectiveness of the signature in predicting PFS was evaluated using the concordance index (C-index) and 95% confidence interval in both the training and the test sets. The time-dependent receiver operator characteristic curve of the radiomics signature was plotted and the area under the curve (AUC) was calculated. A calibration curve was used to assess the difference between the predicted probability of the radiomics signature and the observed probability at different time points. RESULTS: The radiomics signature was composed of six features, which achieved a C-index of 0.733 (95% confidence interval 0.664-0.803) in the training set and 0.734 (95% confidence interval 0.608-0.861) in the test set. In the training set, the radiomics signature yielded an AUC of 0.707, 0.737, 0.788, 0.859 and 0.829 for 1-, 2-, 3-, 4- and 5-year PFS, respectively. Similarly, the radiomics signature exhibited an AUC of 0.738, 0.807, 0.761, 0.787 and 0.818 for 1-, 2-, 3-, 4- and 5-year PFS, respectively, in the test set. The calibration curves showed no significant difference between the predicted probability of the radiomics signature and the observed probability for up to 5 years. CONCLUSIONS: Computed tomography radiomics features exhibit a significant correlation with the PFS of neuroblastoma patients, particularly in terms of long-term outcomes.

Comparison of anal function and quality of life after conformal sphincter preservation operation and intersphincteric resection of very low rectal cancer: a multicenter, retrospective, case-control analysis.

PURPOSE: Conformal sphincter preservation operation (CSPO) is a sphincter preservation operation for very low rectal cancers. Compared to intersphincteric resection (ISR), CSPO retains more dentate line and distal rectal wall, and also avoids damaging the nerves in the intersphincteric space. This study aimed to compare the postoperative anal function and quality of life between the CSPO and ISR. METHOD: Patients with low rectal cancer undergoing CSPO (n = 117) and ISR (n = 66) were included from Changhai and Huashan Hospital, respectively, between 2011 and 2020. A visual analog scale (range 0-10) was utilized to evaluate satisfaction with anal function and quality of life. The anal function was evaluated with Wexner scores and low anterior resection syndrome (LARS) score. Quality of life was evaluated with the EORTC QLQ-C30 and QLQ-CR38. RESULTS: The CSPO group had more male patients (65.8% vs. 50%, p = 0.042), more preoperative chemoradiotherapy (33.3% vs. 10.6%, p < 0.001), lower tumor position (3.45 ± 1.13 vs. 4.24 ± 0.86 cm, p < 0.001), and more postoperative chemotherapy (65% vs. 13.6%, p < 0.001) compared to the ISR group. In addition, CSPO patients had shorter postoperative stay (6.63 ± 2.53 vs. 7.85 ± 4.73 days, p = 0.003) and comparable stoma reversal rates within 1 year after surgery (92.16% vs. 96.97%, p = 0.318). Multivariable analysis showed that CSPO significantly contributed to higher satisfaction with anal function (beta = 1.752, 95% CI 0.776-2.728) and with quality of life (beta = 1.219, 95% CI 0.374-2.064), but not to Wexner, LARS score, or EORTC QLQ-C30 and QLQ-CR38. CONCLUSION: CSPO improved the satisfaction with anal function and quality of life but utilized more preoperative chemoradiotherapy. CSPO may be an alternative choice for patients with very low rectal cancers in better physical health and with higher requirements for anal function and quality of life.

[Silenced ANP32A inhibits the growth, invasion and migration of colorectal cancer in vitro via the inactivation of AKT pathway].

OBJECTIVE: To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect. METHODS: Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting. RESULTS: Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01). CONCLUSION: ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.

COVID-19 pandemic and its impact on emergency surgery in colorectal cancer: A single centre experience.

INTRODUCTION: The COVID-19 pandemic has led to major changes in the provision of surgical services and also affected patients' health-seeking behaviour. This contributes to delayed presentation of many surgical conditions resulting in poorer outcomes. Colorectal cancer (CRC) patients who present with acute surgical emergencies such as complete bowel obstruction, perforation, bleeding or sepsis often require immediate intervention. This study aimed to assess the impact of COVID-19 pandemic on the proportion of emergency surgery in CRC patients. MATERIALS AND METHODS: This is a retrospective cohort study. All CRC patients who underwent elective and emergency surgery from January until December 2019 (pre-COVID era) and September 2020 until August 2021 (COVID era) were included. Patient demographics, presentation, tumour stage, surgery performed and waiting time for surgery were collected. Data were then compared. RESULTS: Seventy-seven and 76 new cases of CRC underwent surgery before and during COVID-19, respectively. The proportions of emergency surgery before and during COVID-19 are 29% vs 33% (p=0.562). Of those who required emergency surgery, the proportions of patients who required stoma formation are 59% vs 72% (p= 0.351). There was no difference in median waiting time for patients requiring elective surgery (p= 0.668). CONCLUSION: The proportion of emergency surgery for CRC patients is not statistically higher during the pandemic.

[Differential diagnosis model of benign and malignant breast BI-RADS category 4 nodules based on serum SP70 and conventional laboratory indicators].

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.

[Introduction and development of the Trans Woman Voice Questionnaire authorized simplified Chinese translation].

Objective: The purpose of this article is to translate and adapt the Trans Woman Voice Questionnaire (TWVQ) into the simplified Chinese version (TWVQ-SC), and to evaluate its reliability and validity. Methods: Authorized by the author of the TWVQ,the TWVQ-SC was developed through translation, back translation,and cross-cultural adaptation.The TWVQ-SC contained 30 items capturing personal perception of vocal function, psychosocial impact of voice, and degree of limitation in social participation. Subjects included 279 trans women in the experimental group, 128 cis women in the control group, and 89 trans women in the retest group. The Cronbach α and the item total correlation coefficient (ITC) were calculated to examine the internal consistency. The intraclass correlation coefficient (ICC) was chosen to examine the test-retest reliability. Regarding validity, the expert judgment method was utilized to examine the content validity. Factor analysis and Spearman's rank correlation coefficient were used to examine the construct validity, and the discriminant validity was examined by the rank sum test of the total scores of the cisgender and transgender subjects. Results: The Cronbach's α of TWVQ-SC is 0.97 and the ITC of 30 items range from 0.40 to 0.86. The ICC is 0.84. The four principal components' cumulative contribution is 65.12%. The Spearman rank correlation coefficient to VHI-10 is 0.85 (P<0.01). The total score of the TWVQ scale in the transgender female group is significantly higher than that in the cisgender female group (U=1 580,P<0.01). Conclusion: TWVQ-SC demonstrates good reliability and validity and therefore can be used clinically as a self-assessment tool for transgender women to evaluate their own voice.