Objective:The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis.Methods:The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis.Results:A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143).Conclusion:Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

Liver macrophages are important immune cells in the liver,and they express proinflammatory factors and anti-inflammatory factors through polarization into M1 type and M2 type,respectively,thereby playing a role in regulating inflammatory damage response.The malignant transformation of hepatic progenitor cells is the core mechanism of the malignant progression of hepatic precancerous lesions,and its key factor is the continuous stimulation of inflammatory microenvironment,which is closely associated with M1/M2 macrophage polarization.This review mainly focuses on the association between macrophage polarization,chronic inflammation,and malignant transformation of hepatic progenitor cells,so as to provide a theoretical basis for the prevention and treatment of hepatic precancerous lesions.

Objective To observe the effects of Xiaomudan Granules on cholesterol synthesis in rats with non-alcoholic fatty liver disease(NAFLD);To explore its mechanism on the treatment of NAFLD based on mTORC1/USP20/HMGCR pathway.Methods Totally 60 SD rats were randomly divided into blank group,model group,Western medicine group(polyene phosphatidylcholine)and TCM low-,medium-and high-dosage groups(Xiaomudan Granules).The blank group was fed with ordinary diet,and the other groups were fed with high-fat diet for 12 weeks to establish NAFLD rat model.After successful modeling,each administration group was given the corresponding drug intragastric administration,and the blank group and model group were given aseptic distilled water intragastric administration for 4 weeks.Body mass and liver mass of rats were recorded,liver index was calculated,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)contents were detected by automatic biochemical analyzer,the morphological changes of liver tissue were observed by HE staining and oil red O staining,real-time fluorescence quantitative PCR and Western blot were used to detect ribosome S6 kinase(S6K),ubiquitin specific protease 20(USP20),3-hydroxy-3-methylglutaryl CoA reduction enzyme(HMGCR)mRNA and p-S6K,S6K,USP20,HMGCR protein expression in liver tissue.Results Compared with the blank group,the body mass,liver mass and liver index of rats in model group significantly increased(P<0.01,P<0.05),the volume of liver lobe increased,the edge was blunted;the contents of serum ALT,AST,TC,TG and LDL-C significantly increased,while HDL-C content significantly decreased(P<0.01);most hepatocytes showed steatosis,significant vacuole and inflammatory infiltration,increased lipid droplets,and significantly increased mRNA expression of USP20 and HMGCR in liver tissue(P<0.01)and protein expressions of p-S6K,USP20 and HMGCR(P<0.01).Compared with the model group,TCM high-dosage group and Western medicine group could significantly decrease body mass,liver mass and liver index of rats(P<0.01,P<0.05),and improve the appearance of liver;decrease the contents of ALT,AST,TC and LDL-C in serum,and increase the content of HDL-C(P<0.01,P<0.05);alleviate hepatocyte steatosis and balloon-like degeneration,reduce lipid droplet deposition,and decrease USP20,HMGCR mRNA and p-S6K,USP20,HMGCR protein expression in liver tissue(P<0.01,P<0.05).Conclusion Xiaomudan Granules may regulate cholesterol synthesis through mTORC1/USP20/HMGCR pathway,and thus play a role in the treatment of NAFLD in rats.

Objective To explore the mechanism of Yipi Yanggan Prescription in the treatment of precancerous lesion of liver in rats based on M1 type macrophage polarization-chronic inflammation-liver cell malignant transformation.Methods Totally 90 Wistar rats were randomly divided into blank group,model group,Hugan Tablet group and Yipi Yanggan Prescription high-,medium-and low-dosage groups,with 15 rats in each group.The blank group was injected distilled water intraperitoneally,and the other groups were injected 5 mL/kg of diethylnitrosamine intraperitoneally at 50 mg/kg per week(twice per week)for 16 weeks to induce the precancerous lesion of liver model.Starting from the second day of modeling,Yipi Yanggan Prescription high-,medium-and low-dosage groups were orally administered with 1.2,0.6 and 0.3 g/mL Yipi Yanggan Prescription,respectively.The Hugan Tablet group was orally administered with 921 mg/kg Hugan Tablet solution,the blank group and model group were orally administered with an equal amount of physiological saline for 16 consecutive weeks.The appearance of the liver was observed,ELISA was used to detect serum ALT,AST,ALP,AFU,as well as TNF-α,IL-6,iNOS and MCP-1 content,HE staining and Masson staining were used to observe the morphology of liver tissue,immunohistochemistry was used to detect the expressions of liver cell malignancy markers OV6,CK19,CD133 and EpCAM,qPCR was used to detect the mRNA expressions of CK19,CD133 and EpCAM in liver tissue,immunofluorescence co-localization was used to detect the co-expressions of M1 type macrophage markers CD68 with IL-6 and TNF-α.Results Compared with the blank group,the liver of the model group rats was hard,with a rough surface and dull edges,and a large number of nodules were visible,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 significantly increased(P<0.01),there were large areas of dysplasia nodules,inflammatory cell infiltration,and increased collagen fibers in liver tissue,the expressions of OV6,CK19,CD133 and EpCAM in liver tissue significantly increased,and the co-expressions of CD68 with IL-6 and TNF-α significantly increased(P<0.01).Compared with the model group,the number and size of liver nodules in each treatment group of rats decreased,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 were significantly decreased(P<0.01),hepatocellular dysplasia and inflammatory cell infiltration were significantly improved,collagen fibers decreased,and the expressions of OV6,CK19,CD133 and EpCAM in liver tissue were significantly decreased,the co-expressions of CD68 with IL-6 and TNF-α significantly decreased(P<0.05,P<0.01).Conclusion Yipi Yanggan Prescription may alleviate inflammation by inhibiting polarization of M1 type macrophages,improve liver cell malignancy,and exert therapeutic effects on rats with precancerous lesion of liver induced by diethylnitrosamine.

Objective:To investigate the application value of intrathoracic double-flap tech-nique (Kamikawa anastomosis) in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with esophagogastric junction cancer who were admitted to the First Affiliated Hospital of Xiamen University between July 2022 and April 2023 were collec-ted. There were 7 males and 3 females, aged 62(range, 53-71)years. All the 10 patients underwent combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer. Reconstruction was performed with an intrathoracic Kamikawa anastomosis. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3) follow-up and survival. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative and postoperative situations. All the 10 patients underwent surgery successfully. The operation time and volume of intraoperative blood loss were (347±41)minutes and (91±41)mL. The time to postoperative fluid diet intake, time to removal of postoperative abdominal drainage tube, time to removal of postoperative chest drainage tube, duration of postoperative hospital stay were (4.3±1.1)days, (5.0±1.6)days, (10.5±3.9)days, (13.3±3.8)days. Six patients had postoperative complications, including 1 case of Clavien-Dindo grade ⅢB, 3 cases of Clavien Dindo grade Ⅱ, 2 cases of Clavien Dindo grade Ⅰ. An upper gastrointestinal contrast at postoperative day 7 showed no anastomotic leak or anastomotic stricture in the 10 patients. (2) Postoperative pathological examination. Results of postoperative pathological examination in the 10 patients showed negative surgical margin. The number of lymph node dissected was 22±6. There were 3 patients with 5 positive lymph nodes. The tumor diameter and distance from center of tumor to squamocolumnar mucosal junction were (3.3±0.5)cm and (1.9±1.4)cm. One patient had tumor differentiation degree as high and moderate differentiation, 5 cases as moderate differentiation, 3 cases as moderate and low differentiation, 1 case as low differentiation. There were 5 patients with squamous cell carcinoma of the esophagogastric junction and 5 patients with adenocarcinoma of the esophagogastric junction. (3) Follow-up and survival. All the 10 patients were followed up for 7(range, 3?12)months, achieving disease-free survival. The visick quality of life grade Ⅰ, Ⅱ, Ⅲ, Ⅳ were observed in 7, 3, 0, 0 patients. Postoperative gastroscopy was completed in 7 patients, in which mild anastomotic strictures were noted in 2 patients, but no treatment was required. There was no reflux esophagitis.Conclusion:Intrathoracic Kamikawa anastomosis in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer is safe and feasible, with satisfactory short-term efficacy.

Objective:To investigate the effect of cumulative serum uric acid (cumSUA) on early-onset ischemic stroke in young adults.Methods:A prospective cohort study was conducted. A total of 15 607 Kailuan workers who participated in at least two physical check-ups in 2006 and 2008 and at the time of the last physical check-up before 2014 were selected as subjects. Cumulative uric acid exposure during the follow-up period was calculated. The subjects were divided into three groups according to the quantile of cumSUA: the first quantile group was cumSUA<1 563 μmol/L·year, the second quantile group was: 1 563 μmol/L·year≤cumSUA<1 996 μmol/L·year, the third group was cumSUA≥1 996 μmol/L·year. The time of the last physical check-up was regarded as the starting point of follow-up, and early-onset ischemic stroke was regarded as the end event. Kaplan-Meier was used to calculate the incidence of early-onset ischemic stroke in different groups, and Log-rank method was used to calculate the differences in the incidence of early-onset ischemic stroke among different groups. Multivariate Cox regression model was used to analyze the risk of early-onset ischemic stroke in different groups. A four-node (5th, 25th, 75th, 95th percentile) restricted cubic spline plot was used to assess the dose-response relationship between cumSUA and early-onset ischemic stroke.Results:A total of 15 607 subjects were followed up for (7.3±1.1) years. 100 cases with early-onset ischemic stroke were observed with an average age of (46±4) years old. The number of events in the first, second, and third quartile groups was 18, 35, and 47, respectively, and the cumulative incidence rates in the first, second, and third quartile groups were 0.40%, 0.77%, and 1.07%, respectively. The difference in cumulative incidence of endpoint events between the groups was statistically significant by Log-rank test ( χ2=14.96, P=0.003). The results of Cox regression analysis showed that after correcting for confounders, the HR(95% CI) for early-onset ischemic stroke in the second and third quartile groups was [1.67(0.92,3.00), P=0.090; 2.05(1.48,3.69), P=0.020]. Restricted cubic spline results showed a nonlinear correlation between cumSUA and early-onset ischemic stroke after adjysted for confounders. Conclusion:Cumulative serum uric acid is positively correlated with the risk of early-onset ischemic stroke in young adults.

ObjectiveLipopolysaccharide （LPS）-induced zebrafish inflammation model was used to evaluate the anti-inflammatory activity of different extracts from Lianggesan （LGS） and its component Glycyrrhiza Radix et Rhizoma. MethodDifferent polar fractions of LGS and Glycyrrhiza Radix et Rhizoma were obtained by the principle of similar miscibility. For toxicity observation， the zebrafish （3 day-post-fertilization） was exposed to different concentrations of extracts for 24， 48 and 72 h. The yolk sac of the zebrafish was microinjected with 0.5 g·L^-1 LPS to establish the inflammation model， and then the embryos were soaked with different concentrations of extracts to observe their survival status at 72 h and the aggregation of neutrophils in yolk sac at 12 h after treatment. Hematoxylin-eosin staining was used to analyze the yolk sac of the zebrafish microinjected with LPS. Quantitative Real-time polymerase chain reaction （Real-time PCR） was performed to further investigate the anti-inflammatory effects and mechanisms of LGS and Glycyrrhiza Radix et Rhizoma. ResultThe toxicity of LGS and Glycyrrhiza Radix et Rhizoma was decreased with the increase of polarity， and the descending order was petroleum ether>ethyl acetate>n-butanol>water. Compared with model group， the extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma prolonged the survival time of the zebrafish， and inhibited the recruitment and aggregation of neutrophils and decreased the infiltration of inflammatory cells in the yolk sac， among which the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma had the most significant effect （P<0.01）. In addition， compared with model group， the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma down-regulated the mRNA expression of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， and suppressed the expression of toll like receptor 4 （TLR4） and nuclear factor kappa-B （NF-κB） in LPS-stimulated zebrafish （P<0.01）. ConclusionThe extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma exerted protective effects in LPS-induced zebrafish by inhibiting the TLR4 and NF-κB signaling pathways. Moreover， in zebrafish model， the method of administration by soaking was applicable to the high-throughput screening of anti-inflammatory Chinese medicine， which was suitable for the evaluation of anti-LPS activity of Chinese medicine and the different extracts.

Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

Objective:To identify the risk factors for acute kidney injury (AKI) after non-cardiac surgery.Methods:Medical records of patients who underwent non-cardiac surgery with general anesthesia in our hospital from October 1, 2016 to March 31, 2021 were collected.AKI was diagnosed using the Kidney Disease Improving Global Outcomes definition of AKI.Multi-factor logistic regression analysis was used to screen the risk factors affecting AKI.Generalized linear regression was used to analyze the factors influencing the difference in serum creatinine before and after surgery.Results:A total of 2 214 patients were eventually enrolled, and the incidence of AKI was 5.15%.The results of multi-factor logistic regression analysis showed that preoperative hypertension, American Society of Anesthesiologists Physical Status classification ≥ Ⅲ, intraoperative bleeding >300 ml, emergency surgery, and grade IV surgery were independent risk factors for AKI after non-cardiac surgery ( P<0.05). The results of generalized line regression analysis showed that preoperative hyponatremia, intraoperative bleeding >300 ml, emergency surgery, and duration of anesthesia were positively correlated with increased difference in serum creatinine before and after surgery ( P<0.05). Conclusions:Preoperative hypertension, American Society of Anesthesiologists Physical Status classification ≥ Ⅲ, intraoperative bleeding >300 ml, emergency surgery and grade IV surgery are independent risk factors for AKI after non-cardiac surgery.