[The pathological characteristics and prognostic analysis of medullary thyroid microcarcinoma].

Objectives: To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). Methods: A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, n=13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, n=48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Results: Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged Mï¼»Q1，Q3ï¼½51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both P>0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all P>0.05). Conclusion: MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.

The influence of respiratory movement on preoperative CT-guided localization of lung nodules.

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

[Relationship between sleep status and occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China].

Objective: To understand the prevalence of occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China, and analyze the relationship between their sleep status and occasional hypertension. Methods: From October to November 2017, a total of 24 842 preschool children from 109 kindergartens in 11 cities in Hubei, Anhui and Jiangsu provinces were selected by intentional sampling method. A self-made questionnaire was used to collect basic information about the subjects, and the sleep status data was collected by the Children's Sleep Habits Questionnaire. Physical examinations were performed on the subjects, and height, weight and blood pressure were measured on-site. The difference in occasional hypertension detection rate among preschool children with different characteristics was compared, and the correlation between sleep status and occasional hypertension detection rate was analyzed by the multivariate logistic regression model. Results: The age of the subjects was (4.4±1.0) years, including 12 729 boys (51.2%). The prevalence of occasional hypertension was 31.8% (7 907/24 842). The prevalence of occasional hypertension among preschool children in three provinces of the middle and lower reaches of the Yangtze River was 31.8%. There were statistically significant differences in the detection rate of occasional hypertension among preschool children of different genders, age groups, family residence, family economic status and parents' education level (all P values<0.05). The detection rate of occasional hypertension in children with less than 10 hours of sleep was higher than those with sufficient sleep, and the difference was statistically significant (P<0.05). The results of multivariate logistic regression analysis showed that after adjusting for factors such as gender, age, family residence, family economic status, parental education level, parental smoking history, and physical constitution, the ORs (95%CI) for less than 10 hours of sleep, turning on the lights while sleeping, and poor sleep quality were 1.09 (1.03-1.15), 1.17 (1.07-1.28) and 1.04 (0.91-1.18), respectively, compared with the corresponding reference group. Conclusion: The detection rate of occasional hypertension is high in preschool children in the middle and lower reaches of the Yangtze River and there is a positive correlation between insufficient sleep and turning on the light when sleeping and occasional hypertension in preschool children.

[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Single-stage computer-assisted approach for tumour resection and functional restoration of Brown class III maxillary defects-titanium mesh and zygomatic implants combined with vascularized anterolateral thigh flap.

The functional restoration of Brown class III maxillary defects is a challenging endeavour in oral and maxillofacial surgery. Conventional reconstruction techniques with osseous free flaps have certain limitations, such as the need for multiple operations and greater patient morbidity. This study introduces a single-stage computer-assisted approach for tumour resection and functional restoration of these defects using titanium mesh, zygomatic implants, and a vascularized anterolateral thigh flap (ALTF). Virtual surgical planning was used to simulate tumour resection, titanium mesh placement, and zygomatic implant insertion. Surgery was performed under the guidance of mixed reality and surgical navigation. The tumour was resected by total hemimaxillectomy, and the reconstruction was performed using a pre-bent patient-specific titanium mesh for the orbital floor and two zygomatic implants placed and exposed through tunnels in an ALTF. The ALTF survived without any perioperative complications. A fixed prosthesis with built-in titanium frame was delivered 4 months postoperatively. At the 1-year follow-up, there was no tumour recurrence, the implants were osseointegrated, and aesthetics and masticatory function were satisfactory. An occlusal force of 155 N was attained on the reconstructed side, compared to 127 N on the non-surgical side.

[Analysis of the 1-year curative efficacy of sleeve gastrectomy, Roux-en-Y gastric bypass, single anastomosis duodenal-ileal bypass with sleeve gastrectomy and biliopancreatic diversion with duodenal switch in patients with super obesity].

Objective: To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity. Methods: In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group (n=16), RYGB group (n=9), SADI-S group (n=9) and BPD/DS group (n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results: All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6-16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 (F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 (F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 (F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 (F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations (P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion: SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Fibulin-1 Regulates Initiation of Successional Dental Lamina.

In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently, we showed that biomechanical stress generated by the rapid growth of the deciduous tooth inhibits SDL development via integrin ß1-RUNX2 signaling at embryonic day 60 (E60) in miniature pigs. However, the mechanism by which RUNX2 regulates SDL initiation within the SDL stem cell niche remains unclear. In the current study, we transcriptionally profiled single cells from SDL and surrounding mesenchyme at E60 and identified the landscape of cellular heterogeneity. We then identified a specific fibroblast subtype in the dental follicle mesenchyme between the deciduous tooth and the SDL of the permanent tooth (DFDP), which constitutes the inner part of the niche (deciduous tooth side). Compared with traditional dental follicle cells, the specific expression profile of DFDP was identified and found to be related to biomechanical stress. Subsequently, we found that RUNX2 could bind to the enhancer regions of Fbln1 (gene of fibulin-1), one of the marker genes for DFDP. Through gain- and loss-of-function experiments, we proved that the biomechanical stress-mediated RUNX2-fibulin-1 axis inhibits the initiation of SDL by maintaining SDL niche homeostasis.

[Effects of cadmium chloride on testicular autophagy and blood-testis barrier integrity in prepubertal male rats].

Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 µmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 µmol/L CdCl(2)), experimental group[10.0 µmol/L CdCl(2)+60.0 µmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 µmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 µmol/L, after exposure to 5.0, 10.0 µmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.

[Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database].

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

[Interpretation for indications of metabolic and bariatric surgery released by ASMBS and IFSO in 2022].

With the increasing number of obese patients worldwide, metabolic and bariatric surgery (MBS) has quickly become an effective way to treat obesity and related metabolic diseases such as type 2 diabetes, hypertension, lipid abnormalities, etc. Although MBS has become an important part of general surgery, there is still controversy regarding the indications for MBS. In 1991, the National Institutes of Health (NIH) issued a statement on the surgical treatment of severe obesity and other related issues, which continues to be the standard for insurance companies, health care systems, and hospital selection of patients. The standard no longer reflects the best practice data and lacks relevance to today's modern surgeries and patient populations. After 31 years, in October 2022, the American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), the world's leading authorities on weight loss and metabolic surgery, jointly released new guidelines for MBS indications, based on increasing awareness of obesity and its comorbidities and the accumulation of evidence of obesity metabolic diseases. In a series of recommendations, the eligibility of patients for bariatric surgery has been expanded. Specific key updates include the following: (1) MBS is recommended for individuals with BMI≥35 kg/m2, regardless of the presence, absence, or severity of co-morbidities; (2) MBS should be considered for individuals with metabolic diseases and BMI 30.0-34.9 kg/m2; (3) the BMI threshold should be adjusted for the Asian population:: BMI≥25 kg/m2 suggest clinical obesity, and BMI ≥ 27.5 kg/m2 population should consider MBS; (4) Appropriately selected children and adolescents should be considered for MBS.

[A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease].

Objective: This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies. Methods: A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed. Results: Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 µg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis (r=0.547, P<0.001). Conclusions: The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Cost-effectiveness analysis of five drugs for treating postmenopausal women in the United States with osteoporosis and a very high fracture risk.

PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

[Cadmium induces apoptosis of mouse spermatocytes (GC-2 spd) by promoting mitochondrial fission].

Objective: To study the underlying mechanism of cadmium-induced apoptosis of mouse spermatocytes (GC-2 spd) . Methods: In March 2021, GC-2 spd cells were exposed to different concentrations of CdCl(2) for 24 hours, namely 5 µmol/L CdCl(2) (low-dose) group and 10 µmol/L CdCl(2) (high-dose) group, and unexposed GC-2 spd cells were used as control group. Mitochondrial morphology was observed in the cells stained with Mito-Track Red CMXRos fluorescent probes by confocal microscopy and the mitochrondrial membrane potential was measured by flow cytometry with JC-1 fluorescent probes. Mitochrondrial proteins, cytosolic proteins and total cellular proteins of GC-2 spd cells were extracted using cell mitochondria isolation kit and RIPA buffer, respectively. The expression of mitochondrial homeostasis regulatory proteins (FIS1 and OPA1), and apoptosis-related proteins (Cytochrome c and cleaved Caspase-3) were examined by Western blot. Results: Compared with the cells in the control group, the relative ratio of JC-1 red/green fluorescence signal in the cells of the low-dose and high-dose CdCl(2) groups decreased significantly (0.740±0.071, 0.570±0.028), with a statistically significant difference (P=0.017, 0.004) ; The morphology of mitochondria changed from long tube to point, and the proportion of cells containing point mitochondria increased significantly (45.1%±3.7% and 25.7%±4.9%), the difference was statistically significant (P=0.005, 0.001) ; The relative expression level of mitochondrial FIS1 in cells of low and high dose CdCl(2) groups was significantly higher (1.271±0.120, 1.693±0.155), the difference was statistically significant (P=0.046, 0.000) ; The relative expression level of OPA1 decreased significantly (0.838±0.050, 0.682±0.040), and the difference was statistically significant (P=0.049, 0.001). Compared with the control group, the relative expression level of cytochrome c protein in the cytoplasm of cells in the low dose group of CdCl(2) was not significantly increased (1.249±0.151), and the difference was not statistically significant (P=0.075). However, the relative expression level in the cytoplasm of cells in the high dose group of CdCl(2) was significantly increased (2.355±0.110), and the difference was statistically significant (P=0.000) ; The relative expression level of Cytochrome c in mitochondria of low and high dose CdCl(2) groups decreased significantly (0.681±0.043, 0.619±0.114), with a statistically significant difference (P=0.004, 0.001) ; Moreover, the level of cleaved Caspase-3 protein in cells gradually increased (5.486±0.544, 11.493±1.739), the difference was statistically significant (P=0.004, 0.000) . Conclusion: Cadmium induced cleaved Caspase-3 mediated apoptosis of GC-2 spd cells via promoting mitochrondrial fission and the release of Cytochrome c from the mitochrondria to the cytosol.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Development and validation of a prognostic model based on SEER data for patients with esophageal carcinoma after esophagectomy].

OBJECTIVE: To develop a nomogram to predict the long-term survival of patients with esophageal cancer following esophagectomy. METHODS: We collected the data of 7215 patients with esophageal carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database during the period from 2004 and 2016. Of these patients, 5052 were allocated to the training cohort and the remaining 2163 patients to the internal validation cohort using bootstrap resampling, with another 435 patients treated in the Department of Cardiothoracic Surgery of Jinling Hospital between 2014 and 2016 serving as the external validation cohort. RESULTS: In the overall cohort, the 1-, 3-, and 5-year cancer-specific mortality rates were 14.6%, 35.7% and 41.6%, respectively. Age (≥80 years vs < 50 years, P < 0.001), gender (male vs female, P < 0.001), tumor site (lower vs middle segment, P=0.013), histology (EAC vs ESCC, P=0.012), tumor grade (poorly vs well differentiated, P < 0.001), TNM stage (Ⅳ vs Ⅰ, P < 0.001), tumor size (> 50 mm vs 0-20 mm, P < 0.001), chemotherapy (yes vs no, P < 0.001), and LNR (> 0.25 vs 0, P < 0.001) were identified as independent risk factors affecting long-term survival of the patients. The nomograms established based on the model for predicting the survival probability of the patients at 1, 3 and 5 years after operation showed a C-index of 0.726 (95% CI: 0.714-0.738) for predicting the overall survival (OS) and of 0.735 (95% CI: 0.727-0.743) for cancer-specific survival (CSS) in the training cohort. In the internal validation cohort, the C-index of the nomograms was 0.752 (95% CI: 0.738-0.76) for OS and 0.804 (95% CI: 0.790-0.817) for CSS, as compared with 0.749 (95% CI: 0.736-0.767) and 0.788 (95%CI: 0.751-0.808), respectively, in the external validation cohort. The nomograms also showed a higher sensitivity than the TNM staging system for predicting long-term prognosis. CONCLUSION: This prognostic model has a high prediction efficiency and can help to identify the high-risk patients with esophageal carcinoma after surgery and serve as a supplement for the current TNM staging system.

[Differential diagnosis and management of hemangioma at geniculate ganglion].

Objective: To investigate the clinical characteristics, differential diagnosis, treatments and prognosis of facial nerve hemangioma and schwannoma at genicular ganglion, so as to provide reference for clinical diagnosis and treatments of facial nerve tumor at genicular ganglion. Methods: Clinical data of 13 patients with facial nerve tumors at genicular ganglion confirmed by postoperative pathology in the Ninth People's Hospital affiliated to Shanghai Jiaotong University School of Medicine from March 2018 to April 2020 were retrospectively analyzed, including seven cases of hemangioma and six cases of schwannoma. There were eight males and five females. Their ages ranged from 20 to 65, with an average age of 40. The course of disease ranged from 3 to 118 months, with an average of 52 months. All the patients underwent preoperative HRCT of the temporal bone and facial nerve dynamic contrast-enhanced(DCE) MRI examinations. All the patients had detailed surgical procedures and at least one-year postoperative follow-up. Results: On HRCT of the temporal bone, (4/7) hemangioma at geniculate ganglion showed characteristic honeycomb appearance, while 6/6 schwannoma and 3/7 hemangiomas showed expansive bone changes. On DCE-MRI, geniculate ganglion hemangioma (7/7) showed characteristic "point-to-surface" enhancement, and schwannoma (6/6) showed characteristic "face-to-surface" enhancement. For five hemangioma-patients with HB-Ⅱ-Ⅳ before surgery, the facial nerve anatomy was completely preserved through transcanal endoscopic approach(TEA), and the facial nerve function improved one year after surgery (two cases of HB-I, two cases of HB-Ⅱ, and one case of HB-Ⅲ). For two patients, with preoperative facial nerve function HB-Ⅴ-Ⅵ, since their tumors was inseparable from the nerves, they were performed with facial nerve anastomosis during the surgery, and the facial nerve function was improved to HB-Ⅳ level one year after surgery. For six patients with meningioma whose facial nerve function was greater than or equal to HB-Ⅲ, based on the preoperative hearing level, the involved segments, and duration of facial paralysis, three of them were conducted surgeries through middle cranial fossa approach, one by translabyrinthine approach, and one via mastoid approach. Two patients among them with complete facial paralysis over three years preoperatively were not performed facial nerve anastomosis after total resections of the tumors, and there was no improvement in facial nerve function one year after surgery. Three patients underwent facial nerve anastomosis after total tumor resections, and their facial nerve function was HB-Ⅲ in one patient, HB-Ⅳ in two patients one year after surgery. One patient (preoperative HB-Ⅲ) had a normal hearing level preoperatively, and the tumor involved the labyrinth segment. To protect the hearing, partial tumor was resected through the middle cranial fossa approach, and facial nerve function improved to HB-Ⅱ one year after surgery. Conclusions: Temporal bone HRCT combined with DCE-MRI are useful for the differential diagnosis of hemangioma and schwannoma at geniculate ganglion and provide references for preoperative clinical decision makings. It is extremely necessary to select the appropriate surgical approach based on the patient's hearing and involved segments. For geniculate ganglion hemangioma, early surgery can improve the possibilities of anatomical integrity of facial nerve, thereby improving facial nerve function postoperatively.TEA is a kind of surgical method worth consideration, with the characteristics of minimally invasive, favorable postoperative features, and so on. For schwannoma, one-stage functional reconstruction of the facial nerve is recommended during the resection of the tumors because of the inevitable damage to the anatomical integrity of the facial nerve.

[Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles].

Objective: To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China. Methods: Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use. Results: Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol (OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol (OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased (OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased (OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant (P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient (P<0.01). Conclusion: For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Incidence and familial clustering of infantile haemangiomas: a multicentre study.

BACKGROUND: The exact incidence of infantile haemangiomas (IH) in the Chinese population is still unknown. A positive family history of IH was considered as a risk factor for the development of IH. OBJECTIVES: This study aims to investigate the incidence of IH in the Chinese population and the mechanism of family history increases the risk for IH development. METHODS: A total of 2489 women and their newborns were enrolled in the prospective study. All newborns were followed up for 12 months to determine whether they developed IH. In addition, 213 IH probands and their 174 siblings were enrolled in the study. The incidence of IH in siblings of the IH probands was investigated. Information regarding risk factors for IH and demographic data were collected on all children. RESULTS: Of the 2572 newborns, 58 IH were identified in 56 (2.2%) newborns. The majority of IH were located on the trunk (46.6%). Siblings of the IH probands were at increased risk for the development of IH (P = 0.024, relative risk 2.451), and the occurrence of prenatal risk factors for IH(P = 0.003) compared with the general population. CONCLUSIONS: Our study showed that the incidence of IH is 2.2% in the Chinese population. Siblings of the individuals with IH were at increased risk for the development of IH may be related to the family clustering of prenatal risk factors for IH. Further exploration of the mechanisms and common features of these prenatal risk factors may help to disclose the origin and pathogenesis of IH.