P4HA2 promotes occurrence and progression of liver cancer by regulating the PI3K/Akt/mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the role of proline 4-hydroxylase Ⅱ (P4HA2) in the occurrence and progression of liver cancer.@*METHODS@#GEPIA and Human Protein Atlas database were used to predict the expression of P4HA2 in hepatocellular carcinoma (HCC), and K-M plotter online database was used to analyze the relationship between P4HA2 expression and the prognosis of HCC. We also examined the expressions of P4HA2 in HCC cells and normal hepatocytes using qRT-PCR and Western blotting. With lentivirus-mediated RNA interference, P4HA2 expression was knocked down in hepatoma SNU-449 and Hep-3B cells, and the changes in cell proliferation, migration and invasion were assessed using cell counting kit-8 (CCK-8) assay, colony formation test, scratch test and Transwell assay. The changes in the expressions of epithelial-mesenchymal transition (EMT) and PI3K/Akt/mTOR signal pathway-related proteins were detected using Western blotting.@*RESULTS@#Online database analysis showed that the expression of P4HA2 was significantly higher in HCC tissues than in normal liver tissues (P < 0.05). The expression levels of P4HA2 mRNA and protein were also significantly higher in HCC cell lines than in normal hepatocytes (P < 0.01). Lentivirus-mediated RNA interference of P4HA2 significantly lowered the expression levels of P4HA2 mRNA and protein in the hepatoma cells (P < 0.05) and caused obvious inhibition of cell proliferation, migration and invasion. P4HA2 knockdown significantly increased the expression of E-cadherin protein, lowered the expressions of N-cadherin and Snail, and obviously decreased the expressions of phosphorylated PI3K, AKT and mTOR (P < 0.05).@*CONCLUSION@#P4HA2 enhances the proliferation, migration, invasion, and EMT of hepatoma cells by activating the PI3K/Akt/mTOR signaling pathway to promote the occurrence and progression of liver cancer.

Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

Clinicopathological features of NTRK3 gene rearrangement papillary thyroid carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.

Study on the susceptibility genes that mediate the resistance of Helicobacter pylori to clarithromycin and levofloxacin based on comprehensive antibiotic research database comparison / 中华消化杂志

Objective:Taking clinical strains of Helicobacter pylori ( H. pylori) with different antimicrobial resistance as the research object, to explore the new genes related to the resistance of H. pylori to clarithromycin (CLA) and levofloxacin (LVX) based on whole-genome sequencing. Methods:From September 1st, 2016 to August 31st, 2019, 1 749 patients with upper gastrointestinal symptoms and positive 13C urea breath test who visited the Department of Gastroenterology and Hepatology, the University of Hong Kong-Shenzhen Hospital were enrolled. After gastric mucosal biopsy, H. pylori was isolated and cultured from gastric mucosa. Ninety H. pylori strains were successfully preserved. According to the results of in vitro drug sensitivity test, a total of 40 strains including 10 strains with single-drug resistance to CLA (CLA group), 10 strains with single-drug resistance to LVX (LVX group), 10 strains with dual-resistance to CLA and LVX (dual resistance group) and 10 strains sensitive to CLA, LVX, amoxicillin, furazolidone, tetracycline and metronidazole (all sensitive group) were screened out. By whole-genome sequencing and comparison to the comprehensive antibiotic research database (CARD), single nucleotide variations (SNV) and indels were analyzed, genes related to H. pylori resistance to CLA and LVX were screened out and the differences of new genes among 4 groups were analyzed. Independent sample t test, one-way analysis of variance, least significant difference method and chi-square test were used for statistical analysis. Results:Among the 4 groups there were no statistically significant differences in the number of SNV (74 952.00±8 755.21, 77 128.10±3 191.35, 78 639.90±601.23 and 77 474.60±2 421.05) and Indels (2 582.20±265.45, 2 653.60±108.37, 2 667.10±43.82 and 2 641.10±80.25) (all P>0.05). Compared to CARD, a total of 223 drug resistance-related genes were detected, of which 19 genes related to CLA mono-resistance in CLA group, 24 genes related to LVX mono-resistance in LVX group, 16 genes related to CLA mono-resistance, 14 genes related to LVX mono-resistance, and 12 dual resistance-related genes in dual resistance group, and 11 genes related to CLA mono-resistance, 17 genes related to LVX mono-resistance, and 13 dual resistance-related genes in all sensitive group. Among the genes related to CLA mono-resistance, the detection rates of erythromycin esterase gene ( ere)B in CLA group, LVX group, dual resistance group and all sensitive group were 0/10, 0/10, 3/10, 0/10, respectively, and the difference was statistically significant( χ2=5.79, P=0.049). The detection rate of erythromycin ribosomal methylase gene ( erm) family in CLA group and dual resistance group was higher than that in LVX group and all sensitive group (45.0%, 9/20 vs. 10.0%, 2/20), and the difference was statistically significant ( χ2=6.14, P=0.013). The detection rates of free methionine-(R)-sulfoxide reductase gene ( msrC) in CLA group, LVX group, dual resistance group and all sensitive group were 10/10, 7/10, 6/10, 4/10, respectively, and the difference was statistically significant ( χ2=8.97, P=0.030). Among the genes related to LVX mono-resistance, the detection rate of quinolone resistance pentapeptide repeat protein gene ( qnr) family in LVX group and dual resistance group was higher than that in CLA group and all sensitive group (60.0%, 12/20 vs. 25.0%, 5/20), and the difference was statistically significant ( χ2=5.01, P=0.025). The detection rates of qnrB4 in CLA group, LVX group, dual resistance group and all sensitive group were 1/10, 3/10, 7/10, 1/10, respectively, and the difference was statistically significant ( χ2=10.17, P=0.010). The number of efflux transporter genes related to CLA mono-resistance in 4 groups were less than those of LVX mono-resistance and dual drug resistance (11 vs. 29 and 11 vs. 23), and the differences were statistically significant ( χ2=11.87, 5.80; P=0.001, 0.016). The detected numbers of LVX resistance-related efflux transport genes in CLA group, LVX group, dual resistance group and all sensitive group were 28, 40, 24 and 27, respectively, and the difference was statistically significant ( χ2=10.26, P=0.016). Conclusions:Erm family and msrC may be important genes that mediate the resistance of H. pylori to CLA, and qnr family is related to mediating the resistance of H. pylori to LVX. Efflux transport genes may play a synergistic role in the process of drug efflux, and are more likely to mediate H. pylori resistance to LVX.

Analysis of intrinsic capacity and influencing factors in community-dwelling elderly people / 中华老年医学杂志

Objective:To investigate the level of intrinsic capacity in community-dwelling elderly people and the influencing factors, in order to provide supporting evidence for the improvement of intrinsic capacity, formulation of management strategies, and promotion of quality of life for the elderly.Methods:A cross-sectional survey was carried out from November 2020 to December 2020 with 236 community-dwelling elderly people in Beijing, who were recruited through a convenience sampling method.The investigation used questionnaires for general data and influencing factors for intrinsic capacity, and the World Health Organization intrinsic capacity questionnaire.Multivariate logistic regression was used to analyze the influencing factors for intrinsic capacity of the elderly.Results:Among 236 community-dwelling elderly people, 132(55.9%)had fair intrinsic capacity(≥4 points)and 104(44.1%)had poor intrinsic capacity(<4 points), with an average score of(3.39±0.95). Multiple Logistic regression analysis results showed that sex( OR=2.005, 95% CI: 1.093-3.676, P=0.025), age( OR=1.727, 95% CI: 1.043-2.860, P=0.034), social participation( OR=0.321, 95% CI: 0.170-0.604, P<0.001), entertainment( OR=2.073, 95% CI: 1.079-3.985, P=0.029), exercise( OR=2.975, 95% CI: 1.761-3.784, P=0.039), sleep( OR=0.508, 95% CI: 0.265-0.973, P=0.041), and emotions( OR=0.436, 95% CI: 0.196-0.970, P=0.042)were influencing factors for intrinsic capacity of community-dwelling elderly people. Conclusions:The intrinsic capacity of community-dwelling elderly people is in the middle range.Sex, age, social participation, entertainment, exercise, sleep, and emotions can affect intrinsic capacity.Therefore, intervention strategies based on influencing factors and improvement of lifestyles can help maintain good intrinsic capacity and reduce adverse effects of major health events.

Effect of Mirabegron combined with Silodosin on detrusor hyperactivity with impaired contractile / 中国康复理论与实践

@#Objective To observe the clinical effect of Mirabegron combined with Silodosin on detrusor hyperactivity with impaired contractile (DHIC).Methods From September, 2019 to December, 2021, 40 patients with DHIC in the Department of Urology of Beijing Bo'ai Hospital were selected and randomly divided into control group and experimental group, with 20 cases in each group. The control group took Silodosin only, and the experimental group took Mirabegron in addition, for four weeks. The urinary diary, residual urine volume, Overactive Bladder Symptom Score (OABSS) and quality of life (QOL) score were compared before and after treatment.Results A total of 18 patients in the control group and 19 in the experimental group finished the trial. After treatment, the number of night urination per day, the residual urine volume and QOL score improved in the control group (P<0.01); the number of urination per 24 hours, the number of night urination per day, the volume per urination, the residual urine volume, the daily urgency score, the OABSS score and QOL score improved in the experimental group (P<0.01). The number decrease of urination per 24 hours, the volume decrease of per urination, the daily urgency score decrease, the OABSS score decrease and QOL score decrease were more in the experimental group than in the control group (P<0.01). The adverse reactions included palpitations, increased heart rate, dyspareunia, increased blood pressure, gastric discomfort, postural hypotension, and retrograde ejaculation, and there was no significant difference between two groups (P > 0.05).Conclusion The efficacy of Mirabellone combined with Silodosin on DHIC is better than Silodosin only, and there was no significant increase in drug-related adverse effects.

Mechanism of Scutellariae Radix-Paeoniae Radix Rubra Combination of Different Proportions Against Hepatic Fibrosis in Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Scutellariae Radix （SR）-Paeoniae Radix Rubra （PRR） combination of different proportions on the expression of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor κB （NF-κB） and phosphatidylinositol kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathways in liver tissues of rats with hepatic fibrosis and explore the mechanism against hepatic fibrosis. MethodSixty male SD rats of SPF grade were randomly divided into a normal group， a model group， a positive control （silymarin） group， and SR-PRR 1∶1， SR-PRR 1∶2， and SR-PRR 1∶4 groups， with 10 rats in each group. The hepatic fibrosis model was induced in rats except for those in the normal group by intraperitoneal injection of 40% tetrachloromethane （CCl4）-olive oil solution at 3 mL·kg-1， 5 mL·kg-1 for the first time， for 8 weeks， twice per week. After 4 weeks， rats were treated correspondingly at 10 mL·kg-1 by intragastric administration， and the body weight of rats in each group was weighed for 8 weeks. After administration， histopathological changes in the liver were observed. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， hyaluronic acid （HA）， laminin （LN）， albumin （ALB）， alkaline phosphatase （AKP）， and superoxide dismutase （SOD） activities， malondialdehyde （MDA）， and hydroxyproline （HYP） content in liver tissues were detected. The mRNA expression levels of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the model group， SR-PRR combination of different proportions could recover the body weight and improve the pathological injury of the liver. As revealed by enzyme linked immunosorbent assay （ELISA） results， compared with the normal group， the model group showed increased ALT， AST， HA， LN， AKP， MDA， and HYP levels to different degrees （P<0.05）. Compared with the model group， the groups with drug intervention showed decreased levels of ALT， AST， HA， LN， AKP， MDA， and HYP， potentiated SOD activity， and increased level of ALB （P<0.05）. As revealed by Real-time PCR results， compared with the normal group， the model group showed increased mRNA expression of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR （P<0.05）. Compared with the model group， the groups with drug intervention showed reduced mRNA expression of TLR4， MyD88， NF-κB， PI3K， Akt， and mTOR in the liver of rats （P<0.05）. ConclusionSR-PRR combination of different proportions can improve the histopathological injury in liver tissues caused by CCl4， with the optimal effect observed in the SR-PRR 1∶4 group. SR-PRR may inhibit the development of liver fibrosis by inhibiting the expression of TLR4/MyD88/NF-κB and PI3K/Akt/mTOR signaling pathways， thereby alleviating chemical-induced liver injury.

Cell Apoptosis Mechanism and Traditional Chinese Medicine Intervention in Diabetic Peripheral Neuropathy： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy is a common complication of diabetes， and its pathogenesis is complex. Its high morbidity can result in disability， teratogenesis， and death in diabetic patients. At present， the pathogenesis of diabetic peripheral neuropathy has not been clearly elucidated， which may be related to oxidative stress， inflammatory response， microcirculation dysfunction， metabolic abnormalities， etc. Recent studies have found that apoptosis plays an important role in the pathogenesis of diabetic peripheral neuropathy. The three pathways， i.e.， mitochondrial pathway， death receptor pathway， and endoplasmic reticulum pathway， jointly regulate the cell apoptosis in the body. Traditional Chinese medicine， with definite efficacies in the treatment of diabetic peripheral neuropathy， is advantageous in overall regulation and multi-target and multi-pathway treatment. As reported， the active ingredients in Chinese medicine and Chinese medicinal compounds can alleviate diabetic peripheral neuropathy by regulating apoptosis signaling pathways. Furthermore， apoptosis pathways are expected to be potential targets for new drugs against diabetic peripheral neuropathy following oxidative stress. Therefore， this paper， taking apoptosis as the entry point， reviewed the research progress on TCM intervention in diabetic peripheral neuropathy in recent years to provide references for the clinical prevention and treatment of diabetic peripheral neuropathy and the development of new drugs.

Perioperative nursing characteristics and management of oral cancer patients underwent radical resection and flap reconstrution / 中国实用护理杂志

Objective:To analyze the perioperative clinical characteristics of patients with oral cancer underwent radical resection and flap reconstrution and the nursing managements.Methods:From January 2020 to December 2020, 658 patients with oral cancer underwent radical resection and flap reconstrution in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University were retrospectively analyzed. All patients were divided into the elderly group (≥60 years) and the younger group (< 60 years), including 279 cases in the elderly group and 379 cases in the younger group. The perioperative clinical data of the patients were collected, and the perioperative general situation, postoperative complications and influencing factors of complications were analyzed.Results:There were differences between the two groups in the aspects of sex ( χ2 = 12.38, P<0.001), preoperative BMI ( t = 2.43, P = 0.015), smoking history ( χ2 = 18.34, P<0.001), preoperative anesthesia grade ( χ2 = 25.61, P = 0.001), preoperative coexisting disease ( χ2 = 46.97, P<0.001), whether oral floor or tongue cancer ( χ2 = 16.68, P<0.001), whether free flap ( χ2 = 6.81, P = 0.003), operation time ( t = 2.19, P = 0.029), preoperative test index hemoglobin ( t = 4.96, P<0.001), albumin ( t = 5.44, P<0.001), D-dimer( Z = -13.52, P<0.001), calcium levels ( t = 4.07, P<0.001) and postoperative complications ( χ2 = 14.55, P<0.001). Multivariate analysis of postoperative complications showed that the age ( OR = 1.021, 95% CI = 1.005-1.037, P = 0.011), preoperative D-dimer ( OR = 1.219, 95% CI = 1.026-1.447, P = 0.024) and the preoperative coexisting disease ( OR = 1.642, 95% CI = 1.108-2.432, P = 0.013) were the risk factors for the postoperative complications. Multivariate analysis of discharge with tube showed that the age ( OR = 1.017, 95% CI = 1.003-1.031, P = 0.017), preoperative BMI ( OR = 0.917, 95% CI = 0.873-0.963, P = 0.001), whether oral floor or tongue cancer ( OR = 2.135, 95% CI = 1.475-3.091, P<0.001), and operation time ( OR = 1.220, 95% CI = 1.120-1.328, P<0.001) were the related factors for the discharge with tube. Conclusion:In view of the above risk factors, it is beneficial for the physical and mental recovery of patients to pay attention to preoperative evaluation, make adequate preoperative preparation, postoperative nursing and observation, improve swallowing function training, prepare for discharge, pay attention to continuous nursing, and establish a tertiary hospital-community-family rehabilitation system.

Exploration on specialty construction of nursing specialty (elderly nursing direction) based on 1+X certificate system / 中国实用护理杂志

Objective:To explore the "Trinity" professional construction path of 1 + X elderly care and 1+ X dementia elderly care and nursing (elderly nursing direction), solve the problem that the three are difficult to be effectively compatible in the process of professional talent training, and cultivate more compound technical talents with "one specialty and multiple abilities" to meet the needs of aging society.Methods:In June 2021, 50 students from class 1 of 2020 nursing major (elderly nursing direction) of Pingxiang health vocational college were selected as the experimental group and 50 students from class 2 were selected as the control group. The nursing students in the experimental group were taught and trained by the newly revised talent training scheme, curriculum standards and a series of corresponding teaching reform measures. The students in the control group were trained by the conventional mode. After the course of the third semester, the passing rate of 1+X elderly care, the passing rate of 1+ X dementia elderly care and the score of geriatric nursing core competence evaluation scale were compared and analyzed between the two groups.Results:The total score of the test group was 156.60 ± 6.00 and that of the control group was 140.86 ± 9.20. The difference was statistically significant ( t=10.13, P<0.05). The passing rate of 1+ X elderly care in the experimental group was 96.43%(27/28), and that of 1 + X elderly care in the control group was 11/15. The difference was statistically significant ( χ2=5.07, P<0.05). The passing rate of care for the elderly with 1 + X dementia was 95.45%(21/22), and the passing rate of care for the elderly with 1 + X dementia was 8/13, the difference was statistically significant ( χ2=4.45, P<0.05). Conclusions:Based on the "Trinity" professional construction mode of nursing specialty (geriatric nursing direction) under the 1 + X certificate system, it can improve students′ core competence of geriatric nursing, improve the passing rate of vocational skill level certificate, and provide reference for the professional construction of nursing specialty (geriatric nursing direction) in medical and health higher vocational colleges.

Strengthening the diagnosis and treatment of metabolic associated fatty liver disease in breast cancer patients / 中华内分泌外科杂志

Metabolic-dysfunction associated fatty liver disease (MAFLD) is a common concomitant disease of breast cancer. It is one of the main causes of liver damage during chemotherapy and also an important cause of liver damage during endocrine therapy or follow-up, which seriously affects the quality of life and prognosis of breast cancer patients. Nonalcoholic fatty liver disease was renamed as MAFLD, which changed the original "exclusive diagnosis" to "inclusive diagnosis" and the non-negligible role of metabolic factors in the occurrence and development of fatty liver disease was recognized, but the clinical attention is not enough at present. More attention should be paid to the diagnosis and treatment of MAFLD in breast cancer patients because the proportion and risk of metabolic disorders are higher than that in general people. In this article, we will focus on the clinical significance, prevention and treatment of the new definition of MAFLD in the comprehensive management of concomitant diseases of breast cancer, so as to further improve the quality of life and prognosis of breast cancer patients.

Clinical study of parathyroidectomy with small incision in the lateral cervical region / 中华内分泌外科杂志

Objective:To evaluate the clinical feasibility, safety, and advantages of small lateral cervical incision for parathyroid exploration and resection.Methods:A total of 31 consecutive patients who underwent parathyroidectomy with a small lateral cervical incision, in the Department of Endocrinology and Breast Surgery of the First Affiliated Hospital of Chongqing Medical University from Apr. to Nov. 2021, including 11 males and 20 females, aged (49.32±13.79) years, ranging from 28 to 86 years, were selected to make retrospective statistical analysis of the surgical time, hospital stay, intraoperative blood loss, postoperative drainage and postoperative complications of the patients. All patients were injected with carbon nanoparticles suspension injection guided by color ultrasound to locate the enlarged parathyroid gland before surgery. EXCEL 2019 software was used for statistical analysis.Results:Thirty-one patients underwent parathyroidectomy through a small lateral cervical incision. Primary hyperparathyroidism was performed in 19 cases (including 2 cases with bilateral small lateral cervical incision, 2 cases with unilateral excision of thyroid mass combined with parathyroidectomy, 1 case with resection of huge parathyroid adenoma, and 1 case with local anesthesia) . Twelve patients with secondary hyperparathyroidism underwent total parathyroidectomy through bilateral small lateral cervical incision and forearm autogenous parathyroid transplantation (including bilateral thyroid mass resection combined with bilateral total parathyroidectomy and forearm autogenous parathyroid transplantation in 2 cases, local anesthesia and cervical plexus nerve block in 2 cases, and ectopic parathyroid gland in thyroid in 1 case) . Among them, the average operative time of patients with primary hyperparathyroidism was (54.74±27.71 & 74.14±31.73) min, the average intraoperative blood loss was (8.11±5.05 & 14.43±10.94) ml, the average postoperative drainage was (14.37±24.64 & 26.36±32.87) ml, the average postoperative parathyroid hormone was (11.59±16.46 & 26.65±56.38) pg/ml, the average hospital stay was (10.00±5.09 & 10.96±4.55) d, and the postoperative complication rate was (3.2% & 0%) .Conclusions:Parathyroid gland exploration and resection through small lateral cervical incision is a safe and effective surgical method and can also complete thyroid exploration and parathyroidectomy at the same time. Appropriate anesthesia should be selected after a full assessment of the patient’s basic condition.

The role of Caspase-1/GSDMD-mediated cell pyroptosis in anti-tumor effect of cisplatin in triple-negative breast cancer / 中华内分泌外科杂志

Objective:To investigate the role of Caspase-1/gasdermin D (GSDMD) -mediated cell pyroptosis in anti-tumor effect of cisplatin (DDP) in triple-negative breast cancer (TNBC) .Methods:HE staining and immunohistochemical staining were performed to detect the morphological changes and the expression of pyroptosis/apoptosis pathway related proteins in TNBC tissues before and after DDP-based neoadjuvant chemotherapy (NACT) . The TNBC cell line MDA-MB-231 was treated with DDP and the morphological changes were observed. The type of cell death induced by DDP was analyzed by Annexin V-FITC/PI double staining and flow cytometry. Lactate dehydrogenase (LDH) release assay and ELISA were performed to detect the release of LDH and inflammatory factors (IL-18 and IL-1β) in cell culture supernatant after DDP treatment. Western blot (WB) was performed to detect the expression of pyroptosis/apoptosis pathway related proteins in cells after DDP treatment. MDA-MB-231 cells treated with DDP were co-treated with caspase-1 specific inhibitor to inhibit pyroptois or co-treated with caspase-3 specific inhibitor to inhibit apoptosis. The effect of caspase-1 inhibitor or caspase-3 inhibitor on the anti-tumor effect of DDP was detected by MTT assay, clone formation assay, transwell assay and would healing test.Results:Reactive changes in the breast surgical specimen after DDP-based NACT included cell swelling and inflammatory cell aggregation around the tumor bed, which were more similar to pyroptosis. The up-regulation of key molecules of pyroptosis pathway post-NACT was significantly higher than that of key molecules of apoptosis pathway. Further experiments in vitro showed that DDP could induce MDA-MB-231 cells to show pyroptosis-like changes characterized by large bubbles blowing from the cellular membrane. Flow-cytometry analyses showed that the death type of MDA-MB-231 cells caused by DDP was mainly Annexin V +PI + cells (mainly lytic cells, such as pyroptosis) . Additionally, DDP treatment induced significant activation of caspase-1 and GSDMD, increased the release of LDH, IL-18 and IL-1β, however, the activation level of caspase-3, which dominates the apoptosis pathway, was significantly lower than that of caspase-1/GSDMD. Moreover, caspase-1 inhibitors (blocking the classical pyroptosis pathway) had a significantly greater inhibitory effect on the anti-tumor effect of DDP than caspase-3 inhibitors (blocking the apoptosis pathway) . Conclusion:Caspase-1/GSDMD mediated pyroptosis may play a leading role in the anti-tumor effect of DDP in triple-negative breast cancer.

Strengthening the prevention and treatment of hungry bone syndrome, parathyroid hyperfunction and hyperparathyroidism of thyroid cancer patients after thyroidectomy / 中华内分泌外科杂志

Differentiated thyroid cancer is one of the most common endocrine malignant tumors, and thyroidectomy is its basic treatment measures. Insufficient attention is paid to its postoperative bone hungry syndrome and parathyroid hyperfunction or hyperparathyroidism, which will seriously affect the patient’s life quality and prognosis. This paper will explore the etiology, dangers, diagnosis, prevention, and treatment for hungry bone syndrome, parathyroid hyperfunction and hyperparathyroidism of thyroid cancer patients after thyroidectomy.

Risk Factors Predicting Upper Urinary Tract Damage in Patients With Myelodysplasia: Data Analysis of 637 Cases From A Single Center / 대한배뇨장애요실금학회지

Purpose@#To determine the risk factors predicting upper urinary tract (UUT) damage using a grading system for upper urinary tract dilation (UUTD) and a descriptive system for all urinary tract dysfunction (AUTD) in patients with myelodysplasia. @*Methods@#Six hundred thirty-seven patients with myelodysplasia were evaluated at our center from January 2008 to November 2019. Clinical data, ultrasonography, magnetic resonance urography, and video-urodynamics (VUDS) parameters were collected. Univariate and multivariate analyses were used to determine the risk factors predicting UUT damage. @*Results@#Three hundred eighty-three males and 254 females were included. The average course of lower urinary tract symptoms (LUTS) was 14.08±7.07 years (range, 3–31 years). The urodynamic diagnoses of all patients were as follows: detrusor overactivity, 26.8%; detrusor underactivity, 6.44%; and acontractile detrusor, 66.72%. UUT damage was determined in 66.56% of the patients. Of the patients, 28.73 % had vesicoureteral reflux (VUR) during filling (bilateral, n=50; unilateral, n=133) on fluoroscopy during VUDS testing. Two hundred thirty-four patients had UUTD (bilateral, n=203; unilateral, n=31). The occurrence of hydronephrosis based on ultrasonography was closely related to ipsilateral VUR (P<0.05). Absent of bladder sensation, long-term course of LUTS, decreased maximum cystometric capacity (MCC) and bladder compliance (BC), and increased postvoid residual urine (PVR) were shown to be independent risk factors in logistic regression analysis. @*Conclusions@#This retrospective study using UUTD and AUTD systems indicated that patients with myelodysplasia have a high incidence of UUT damage. Absence of bladder sensation, long-term course of LUTS, decreased MCC and BC, and increased PVR were independent risk factors predicting UUT damage.

Optimization and screening of carrier for solid dispersion of olaparib based on the solubility parameter and differential scanning calorimetry / 药学学报

Solid dispersion, a dispersion system in which drug molecules are highly dispersed in carrier materials, has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs. The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion. Therefore, the selection of carrier types and the optimization of drug loading are very important. In the current study, the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib (OLP) and different carriers (VA64, Soluplus, Plasdone S630 and Kollidon K29/32). Besides, the carrier material with good miscibility was experimentally screened by differential scanning calorimetry (DSC). The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier. Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best, and the drug loading of 30% could meet the requirements of large drug loading and physical stability. Polarizing light microscope, X-ray powder diffraction, DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system. Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP. In this study, theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading, which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.

A randomized controlled study on the effect of linaclotide with polyethylene glycol in bowel preparation / 中华消化杂志

Objective:To evaluate the efficacy and safety of linaclotide with polyethylene glycol in bowel preparation.Methods:From September 2021 to February 2022, 240 patients who visited the Department of Gastroenterology, Third People′s Hospital of Hubei Province, Jianghan University and underwent colonoscopy were selected. According to the random number table, in the ratio of 1 to 1, the patients were divided into the linaclotide with polyethylene glycol group and the simple polyethylene glycol group, with 120 cases in each group. The patients in the linaclotide with polyethylene glycol group took 580 μg linaclotide and 2 L polyethylene glycol electrolyte powder solution, and the patients in the simple polyethylene glycol group took 3 L polyethylene glycol electrolyte powder solution. The Boston bowel preparation scale(BBPS) score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the time of the first defecation, the frequency of defecations, the success rate of cecal intubation, the occurrence of adverse effects and the satisfaction rate of patients were compared between the 2 groups. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 235 patients completed bowel preparation and accepted colonoscopy. There were no statistically significant differences in the BBPS score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the success rate of cecal intubation and the frequency of defecations between the linaclotide with polyethylene glycol group and simple polyethylene glycol group(7.3±1.1 vs. 7.0±1.2; 58.1%, 68/117 vs. 60.2%, 71/118; 38.5%, 45/117 vs. 39.8%, 47/118; (4.2±1.9) min vs.(4.3±1.6) min; (5.9±2.7) min vs.(6.2±2.4) min; 100.0%, 117/117 vs. 100.0%, 118/118; 5.3±2.3 vs. 5.1±2.7; all P>0.05). The rate of adverse effects of the linaclotide with polyethylene glycol group was lower than that of simple polyethylene glycol group(25.6%, 30/117 vs. 39.8%, 47/118), the satisfaction rate of patients was higher than that of the simple polyethylene glycol group (93.2%, 109/117 vs. 76.3%, 90/118), and the differences were statistically significant( χ2=0.24 and 0.64, P=0.018 and 0.031). Conclusion:Compared with the 3 L polyethylene glycol regimen, 580 g linaclotide with 2 L polyethylene glycol regimen can achieve the same bowel preparation effect with higher safety and patient satisfaction, which is worthy of clinical application.

Common variant immunodeficiency: a case series and literature review / 中华全科医师杂志

Objective:To analyze the clinical manifestation, laboratory examination, treatment and prognosis of common variable immunodeficiency (CVID) in single center of Chinese population.Methods:The clinical data of 75 cases of CVID, diagnosed according to European Society for Immunodeficiency (ESID) criteria and admitted in Peking Union Medical College Hospital from January 1983 to May 2021 were retrospectively analyzed.Results:The main clinical manifestations of CVID were respiratory abnormality (68.0%,51/75), blood system abnormality (66.7%,50/75), liver and spleen involvement (66.7%,50/75), gastrointestinal abnormality (46.7%,35/75), autoimmune abnormality (29.3%,22/75). Immunoglobulin decreased significantly (median IgG 2.4 g/L, median IgA 0.1 g/L, median IgM 0.1 g/L). Lymphocyte subsets indicated that CD4 +T cells decreased (median 471/μl), CD8 +T cells increased (median 620/μl), CD4 +/CD8 +T calls proportion inverted (median 0.7), and NK cells and B cells decreased (median 44/μl, 115/μl, respectively). During hospitalization, their conditions were improved after IgG replacement therapy, supplemented with anti-infection and nutritional support therapy. Forty seven discharged patients were followed up, and only 16 patients insisted on regular IgG replacement therapy after discharge. Conclusions:The clinical manifestations of CVID are varied, and multiple systems may be involved, including autoimmune abnormalities. The treatment based on IgG replacement has a certain curative effect.

Long term follow up outcome of artificial urinary sphincter implantation to treat stress urinary incontinence / 中华泌尿外科杂志

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

Augmentation uretero-enterocystoplasty for lower urinary tract dysfunction: a long-term retrospective efficacy study / 中华泌尿外科杂志

Objective:To investigate the long-term efficacy and complications of augmentation uretero-enterocystoplasty (AUEC).Methods:The clinical data of 262 patients with lower urinary tract dysfunction who underwent AUEC at our center from January 2003 to June 2022 were analyzed retrospectively. There were 193 males and 69 females, the median age was 24 (4, 67) years, the median disease duration was 12.0 (0.2, 56.0) years and the preoperative creatinine was 91.5 (68.1, 140.0) μmol/L. 320 ureters had high-grade UUTD, 216 ureters had VUR, 14 of which had low-pressure reflux.The number of low-grade VUR ureter was 22 (10.2%) and the number of high-grade VUR ureter was 194 (89.8%). Video-urodynamics showed that the maximum bladder capacity was 102 (47, 209) ml, the maximum detrusor pressure was 33.0 (15.5, 50.5) cmH 2O, and the bladder compliance was 6.4 (3.0, 12.3) ml/cmH 2O. All patients underwent AUEC. The surgical method is to cut a segment of sigmoid colon, open the sigmoid colon along the mesenteric margin, fold and suture it into " U" or " S" shaped intestinal mesh according to the principle of " detubulization" . At the same time, perform ureteroplasty and replanting, and then anastomosis the intestinal mesh with the opened bladder flap to form an expanded new bladder. Follow-up was performed via outpatient clinic or telephone. The creatinine, maximum bladder capacity, maximum detrusor pressure, bladder compliance, ureteral reflux and upper urinary tract dilatation were compared preoperatively and postoperatively. The postoperative complications were also evaluated. Results:The median follow-up time was 57.4 (4, 151) months after surgery. At 1-3 months after surgery, the maximum bladder capacity and bladder compliance increased to 303.9% and 189.9% of the preoperative level, and the maximum detrusor pressure decreased to 63.6% of the preoperative level. At 6-10 years after surgery, the maximum bladder capacity and bladder compliance increased to 490.2% and 627.9% and the maximum detrusor pressure decreased to 25.8% of the preoperative level. The UUTD of the patients was significantly reduced after surgery. The number of the high grade UUTD decreased to 116 (116/398, 29.2%) at 1-3 months and 51 (51/274, 18.6%) at 4-6 months. At 6-10 years, the number of the high-grade UUTD decreased to 4 (4/76, 5.3%) ( P<0.001), which was significantly lower than that before operation. The VUR was significantly relieved after operation, and 393 ureters had no VUR at 1-3 months, accounting for 97.8% (393/402) of the total ureters. Sustained remission of VUR was observed during follow-up. 73 ureters had no VUR at 6-10 years, accounting for 96.1% (73/76) of total ureters ( P<0.001). Patients' creatinine decreased to 79.0 (65.0-128.2) μmol/L at 1-3 months postoperatively, with a downward trend but no statistical difference, and creatinine levels were not significantly elevated at any postoperative time point compared with preoperative levels ( P>0.05). Postoperative complications included metabolic acidosis in 26 cases (9.9%), vesicoureteral anastomosis stenosis in 15 cases (5.7%), recurrent urinary tract infection in 16 cases (6.1%), and urinary calculi in 20 cases (7.6%), and intestinal obstruction requiring laparotomy in 8 cases (3.1%), all of them could be improved after treatments. Conclusions:AUEC is a safe and effective method for treating high-grade VUR or VUR with impaired anti-reflux mechanism, high-grade UUTD or UUTD with ureteral or vesicoureteral junction obstruction, and all of the complications can be improved after treatment. This technique can increase the bladder capacity and compliance, reconstruct the anti-reflux mechanism, and release upper urinary tract obstruction. It may play an important role in stabilizing and protecting the residual renal function from further deterioration.