Objective To investigate feasibility and preliminary oncological safety of surgical innovations in breast cancer patients who have undergone nipple-skin-sparing mastectomy (NSSM) for nipple discharge or central lesions and tumors that do not involve the nipple-areola skin. Methods Between May 2018 and November 2023, patients diagnosed with breast cancer presenting nipple discharge or lesions in the central area underwent NSSM. The imaging assessment revealed no involvement of the nipple-areola-skin by the tumor. We performed a surgical removal of the affected mammary duct and simultaneously made a circular incision measuring 3-4 mm in diameter at the apex of the nipple. The study also involved the collection of clinical data, early complications, oncological outcomes and conducting aesthetic analysis of the nipple using the BREAST-Q scale. Results The surgical procedure was conducted on a cohort of 39 female patients at age of 27-57(39.0±7.6) years. The postoperative pathological stages of breast cancer were distributed as follows: stage 0 in 2 patients (5.1%), stageⅠ in 1 patients (2.6%), ⅡA stage in 15 patients (38.5%), ⅡB stage in 21 patients (53.8%). Tumor type: simple carcinoma in situ in 5 patients (12.8%), invasive carcinoma in 14 patients (35.9%), including invasive carcinoma with carcinoma in situ in 20 patients (51.3%). During the median follow-up period of 15.0 (2-66) months, 3 patients (7.7%) developed decolorization caused by mild nipple ischemia; there was no nipple necrosis; 1 patient (2.6%) failed nipple reconstruction (no milk column, the milk column disappeared due to external dressing compression after operation). There were no incision complications, subcutaneous emphysema or intramammary hematoma in all patients. Two patients (5.1%) underwent prosthesis removal and nipple areola excess skin resection because of prosthesis cavity infection and final exposure caused by debridement, dressing change, redrainage and so on. As of April 2024, no tumor recurrence or metastasis was found during the follow-up period. The satisfaction of patients with nipple was 97.4% according to BREAST-Q score. Conclusion The satisfaction of breast cancer patients diagnosed with nipple discharge or lesions in the central area, but without involvement of the nipple areola skin, and who underwent subcutaneous mastectomy with immediate reconstruction is significantly enhanced. Furthermore, there is no increased risk of tumor recurrence or metastasis in short-term.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Neoplasm Staging ; Survival Rate ; Retrospective Studies

Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.
Humans ; Male ; Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/pathology* ; Chromosome Aberrations ; Kidney Neoplasms/pathology* ; Molecular Biology ; Mutation ; Prognosis

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

Objective: To analyze the relationship between school bullying and parent child separation of left behind children, and to provide a theoretical basis for preventing and controlling school bullying of left behind children. Methods: A total of 4 945 children aged 7 to 18 in Shangrao City were selected by stratified cluster random sampling to complete the Chinese version of the School Bullying Experience Questionnaire(C-SBEQ), and the differences of school bullying between left behind and non left behind children were compared. The parent child separation data of 1 791 left behind children was obtained by self designed questionnaire, and the influence of parent child separation characteristics on school bullying of left behind children was analyzed by binary Logistic regression. Results: The rates of school bullying, bully victimization and perpetration of left behind children were 21.3%, 18.3% and 3.0% respectively, which were higher than those of non left behind children(15.4%, 12.7%, 2.7%). And there were statistical significance in the detection rates of school bullying among left behind children in different schooling stages( χ 2=9.82, P < 0.05), the detection rates ranked as follows:21.4% in primary school, 18.9% in junior high school and 14.7% in senior high school. The rate of bullying perpetration among left behind children was significantly higher in boys (4.8%) than in girls (1.0%)( χ 2= 14.69, P <0.05). The rate bully victimization among former left behind children (children with left behind experience) in the younger than 7 years group ( 20.3 %) was higher than that in the older than 7 years group(13.4%)( χ 2=4.79, P =0.03). There was no significant differences in the detection rate of bullying perpetration among the left behind children with different parent child separation experiences ( P >0.05). Control schooling stages, Logistic regression analysis showed that taking former school age left behind children as reference, bully victimization risk of former pre school left behind children was 1.64 times( OR=1.64, 95%CI= 1.04 -2.59, P <0.05). Conclusion School bullying of left behind children is more severce than that of non left behind children. Early occurrence of parent child separation is associated with higher risk of bullying victimization among left behind children.

Objective: To explore the relationship between family structure with adolescents physical and mental health, and to provide a reference for promoting healthy development of adolescents in the family with particular structure. Methods: The stratified random sampling method was used to select 3 941 middle school students aged 13 to 18 years in Shangrao City of Jiangxi Province. Self designed questionnaire, Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Scale (GAD-7) were used to assess family structure, depressive symptoms and anxiety symptoms, participants were divided into underweight or overweight and obesity according to screening for underweight of school age children and screening for overweight and obesity of school age children. Results: The proportion of adolescents with special family structure was 7.0%. Univariate analysis showed that underweight rate of adolescents with divorced parents (31.2%) was higher than that of adolescents whose parents were still married (25.3%) ( χ 2= 3.55 , P <0.05), the detection rate of depressive symptoms in adolescents with special family structure(40.9%) was higher than that in adolescents with typical family structure(34.5%) ( χ 2=4.60, P <0.05). Multivariate analysis showed that the risk of depressive symptoms in adolescents with special family structure was 1.41 times higher than that in adolescents with typical family structure( 95% CI= 1.02-1.79, P <0.05). Conclusion No significant relationships between special family structure with underweight, overweight and obesity, and anxiety symptoms of adolescents are observed,however,special family structures are associated with increased risk of depressive symptoms in adolescents.

Objective: To obtain experience and generate suggestions for reducing average hospital stays, optimizing perioperative management of patients with gastric cancer and improving utilization of medical resources by analyzing the factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery (ERAS). Methods: This was a case-control study. Inclusion criteria: (1) pathologically diagnosed gastric adenocarcinoma; (2) radical surgery for gastric cancer; and (3) complete clinicopathologic data. Exclusion criteria: (1) history of upper abdominal surgery; (2) presence of distant metastasis of gastric cancer or other ongoing neoplastic diseases; (3) concurrent chemoradiotherapy; and (4) preoperative gastric cancer-related complications such as obstruction or perforation. The study cohort comprised 285 eligible patients with hospital stays of ≥30 days (super-long hospital stay group). Using propensity score matching in a 1:1 ratio, age, sex, medical insurance, pTNM stage, and extent of surgical resection as matching factors, 285 patients with hospital stays of < 30 days during the same period were selected as the control group (non-long hospital stay group). The primary endpoint was relationship between pre-, intra-, and post-operative characteristics and super-long hospital stays. Clavien-Dindo grade was used to classify complications. Results: Univariate analysis showed that number of comorbidities, number of preoperative consultations, preoperative consultation, inter-departmental transference, operation time, open surgery, blood loss, intensive care unit time, presence of surgical or non-surgical complications, Clavien-Dindo grade of postoperative complications, and reoperation were associated with super-long hospital stays (all P<0.05). Inter-departmental transference (OR=4.876, 95% CI: 1.500-16.731, P<0.001), preoperative consultation time ≥ 3 d (OR=1.758, 95%CI: 1.036-2.733, P=0.034), postoperative surgery-related complications (OR = 6.618, 95%CI: 2.141-20.459, P=0.01), and higher grade of complications (Clavien-Dindo Grade I: OR = 7.176, 95%CI: 1.785-28.884, P<0.001; Clavien-Dindo Grade II: OR = 18.984, 95%CI: 6.286-57.312, P<0.001; Clavien-Dindo Grade III-IV: OR=7.546, 95%CI:1.495-37.952, P=0.014) were independent risk factors for super-long hospital stays. Conclusion: Optimizing preoperative management, enhancing perioperative management, and surgical quality control can reduce the risk of prolonging average hospital stay.
Humans ; Case-Control Studies ; Retrospective Studies ; Length of Stay ; Stomach Neoplasms/pathology* ; Enhanced Recovery After Surgery ; Gastrectomy/adverse effects* ; Postoperative Complications/etiology*

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified