Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P＞0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.

BACKGROUND: Patients with pulmonary nodules are treated by minimally invasive surgery, and postoperative symptoms have become the main factors affecting patients' emotion and quality of life. This study aimed to analyze the changes of postoperative symptoms in lung cancer patients with pulmonary nodules. METHODS: The clinical data of eighty-eight lung cancer patients admitted to the same medical group of Department of Thoracic Surgery, West China Hospital of Sichuan University from June 2021 to September 2021 were prospectively collected and analyzed. The types and severity of clinical symptoms before operation, on discharge day, 30-day and 90-day after operation were analyzed. RESULTS: The incidence of postoperative symptoms in lung cancer patients was 79.5%, and most patients suffered from mild (54.3%) and moderate (32.9%) symptoms. The main postoperative symptoms of lung cancer patients were pain (55.7%) and cough (37.2%). The incidence of pain at discharge (55.7%) was significantly higher than that at 30-day (23.7%, P=0.01) and 90-day (12.0%, P=0.01) after discharge. The incidence of cough was significantly higher at 30-day (66.1%) and 90-day (66.0%) than that at discharge (37.2%) (P=0.01, P=0.04). CONCLUSIONS The main postoperative symptoms of lung cancer patients with pulmonary nodules are pain and cough. The incidence and severity of pain decreases with time, and the incidence of cough increases but the severity decreased gradually.
Cough/etiology* ; Humans ; Lung Neoplasms/surgery* ; Pain/etiology* ; Pneumonectomy/adverse effects* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects*

OBJECTIVE：To screen the main effective components of Compound Agrimonia pilosula enteritis capsules and targets of enteritis. METHODS ：UHPLC-MS/MS，MWDB database and relevant literature analysis were used to identify main chemical components in methanol extract of Compound A. pilosula enteritis capsules. TCMSP ，PubChem and UniProt database were adopted to predict and screen the active ingredients and their potential targets. GeneCards and OMIM database were used to predict and screen enteritis related targets ；common targets were screened by R language 4.0.2. The chemical components corresponding to the common targets were matched with the chemical components in the methanol extract of the preparation to obtain the main effective components of the preparation. With the help of STRING database and Cytoscape 3.7.1 software，the protein-protein interaction network was constructed ，and the key targets of the preparation were screened by degree. RESULTS ： A total of 48 compounds were identified ，including 13 phenolic acids ，10 alkaloids，8 flavonoids，6 terpenoids，6 other compounds，3 lipids，1 tannin and 1 organic acid. Compared with the network pharmacology data ，apigenin，luteolin，quercetin （3，7-di-O-methylquercetin，Quercetin-3-O-β-D-galactoside，Quercetin-7-O-glucoside，Quercetin-3-O-β-D-glucoside），palmatine， protocatechuic acid- 4-glucoside and 3，4-dimethoxycinnamic acid were the main effective components. The key targets for the treatment of enteritis included RELA ，APP，CCND1，EGFR，INS，ESR1，IL6，NCOA1，CASP8，FOS. CONCLUSIONS ：A total of 9 main effective components （including apigenin ，luteolin，quercetin，etc.）and 10 key targets for enteritis （including RELA，APP，CCND1，etc.）of Compound A. pilosula enteritis capsules are found.

Objective:To investigate the efficacy and safety of cortical-sparing adrenalectomy (CSA) in the treatment of bilateral pheochromocytoma.Methods:The clinical data of 20 patients with bilateral pheochromocytoma treated in Xiangya Hospital of Central South University from January 2004 to December 2019 were analyzed retrospectively, including 10 males and 10 females. The average age of onset was 32.5 (8-51) years. 3 cases had a family history of pheochromocytoma. There were 14 and 6 patients with bilateral synchronous and metachronous onset, respectively. The mean value of vanilmandelic acid (VMA) in 20 cases was (106.4 ± 60.0) μ mol/24h. Preoperative enhanced CT showed a soft tissue mass with uneven enhancement in the adrenal region, with low-density necrosis, which suggested the diagnosis of Pheochromocytoma. All 20 cases underwent CSA under general anesthesia. In 14 cases of bilateral synchronous disease, 9 cases underwent simultaneous operation and 5 cases underwent staged operation; 6 patients with metachronous disease underwent bilateral tumor resection successively. Laparoscopic surgery was performed in 18 cases and open surgery in 2 cases. Through the abdominal or retroperitoneal approach, open the fat capsule around the upper pole of the kidney, free the medial edge of the upper pole of the kidney, expose the adrenal gland and tumor, completely remove the tumor and capsule, ensure that the adrenal tissue is 3-5 mm away from the cutting edge of the tumor, and the reserved cortical size is at least 1 / 3 of the ipsilateral adrenal gland. The central adrenal vein was preserved as much as possible to reduce the damage to the adrenal vascular bed. The operation related data, intraoperative monitoring records, postoperative complications and long-term follow-up results were recorded.Results:All the 20 cases were successfully completed without tumor rupture. The operation time of simultaneous operation and staged operation were (242.3 ± 61.0) min and (137.9 ± 60.3) min, respectively. The number of patients admitted to ICU after operation was 7 and 2, respectively ( P<0.05); The intraoperative bleeding volume was (528.6 ± 355.7) ml and (277.8 ± 264.7) ml, the number of blood transfusion cases were 5 and 2 cases, and the average hospital stay was (7.4 ± 2.0) d and (7.8 ± 3.3) d, respectively ( P>0.05). 20 cases took glucocorticoid orally (prednisone 5 mg, once every 12 hours) after operation. There was no obvious manifestation of adrenocortical dysfunction and Addison's crisis. The hormone was stopped gradually from 2 weeks to 1 month after operation. The average follow-up was 5.4 (1.0-16.0) years. There were 3 cases of recurrence and no metastasis. Gene detection was performed in 10 cases after operation, and 7 cases carried pheochromocytoma RET and VHL pathogenic gene mutations (RET in 2 cases and VHL in 5 cases). Conclusion:Although CSA has a certain risk of recurrence, it avoids hormone replacement and does not increase the risk of metastasis and death. It is recommended for the treatment of hereditary pheochromocytoma, especially bilateral pheochromocytoma.

Objective: To observe the treatment of inflammatory myopathy-associatied cardiomyopathy and its impact on prognosis of disease. Methods: In this single-center retrospective study, 29 cases of inflammatory myopathy-associated cardiomyopathy were collected in Peking Union Medical College Hospital from 1999 to 2016. The clinical data and adverse events during follow up were documented. Among 29 patients there were 11 cases of polymyositis, 8 cases of dermatomyositis, 8 cases of overlap syndrome and 2 cases of nonspecific myositis.All the patients started with sufficiene prednisone (1-2 mg·kg^-1·d^-1). 7 cases received intravenous immune globulin, while 12 cases were prescribed with steroid pulse therapy, 16 cases with methotrexate, 15 cases with cyclophosphamide, 6 cases with cyclosporine A, while 11 cases with combination of immune suppressors (methotrexate plus cyclophosphamide or cyclosporine A). After a median follow up of 4.8 years (2 month to 15 years), 14 cases died including 9 of cardiac death. Patients with cardiac deaths had lower usage percentages of intravenous gamma globulin (0 vs. 7/20, P=0.05) and steroid pulse therapy (1/9 vs. 11/20, P=0.043) than controls. Comparing with controls, patients in the group of adverse events were more prone to choose methotrexate alone rather than combination of immune suppressors (all-cause death: 1/14 vs. 8/15, P=0.014; cardiac death: 0 vs. 9/20, P=0.027). Kaplan-Meier survival analysis showed significant difference of survival rates between patients with combination of immune suppressors and controls (Log Rank χ²=6.001, HR=7.58, P=0.014), as well as between patients with β receptor blockers and controls (Log Rank χ²=4.589, HR=2.95, P=0.032). Conclusions We recommend a management strategy that emphasize both primary disease controlling and cardiac remodeling improvement in patients with inflammatory myopathy-associated cardiomyopathy. On the basis of sufficient glucocorticoids, intravenous gamma globulin, steroid pulse therapy, combination of methotrexate plus other immune suppressants, and β receptor blockers were worthy to be considered.

OBJECTIVE: To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity. METHODS: Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results. RESULTS: NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation. CONCLUSION A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.
Brachydactyly ; complications ; DNA Mutational Analysis ; Humans ; Mutation ; Obesity ; complications ; Pedigree

Objective:The present study was designed to explore the role of ER stress in cardiac hypertrophy of adult APPswe /PS1dE9 transgenic mice.Methods:10 adult APPswe/PS1dE9 transgenic mice and 10 C57BL/6 wild type (WT) mice were divided into the transgenic experimental and control group,WT experimental and control group,respectively,with 5 mice in each group.Experimental groups received a low dose ofIsoproterenol (ISO) (2 mg/kg) once a day for 4 weeks to induce cardiac hypertrophy,while control groups received the same volume of normal saline.After 4 weeks,the mice were anesthetized,followed by,electrocardiogram (ECG) recording and the measurement of the heart rate and body weight before being sacrificed.The heart was dissected out,and the masses of heart and the left ventricle were measured,the left ventricule mass index (LVW/BW) and the whole heart weight ratio (HW/BW) were calculated.HE staining was used to observe the pathological and morphological changes of cardiomyocytes,and Western Blot and immunohistochemistry were used to detect the expressions of ER stress relevant proteins-GRP78,JNK,P-JNK and CaMKII.Results:Compared with WT experimental mice,the ventricular wall in the APPswe/PS1dE9 transgenic experimental mice was apparently hypertrophic after the induction by low doses of ISO,and the HW/BW and the LVW/BW were also significantly increased in the APPswe/PS1dE9 transgenic experimental mice than those in the transgenic control mice,WT experimental and control mice (P＜0.05).HE staining showed that compared with the transgenic control mice,WT experimental and WT control mice,in the adult APPswe/PS1dE9 transgenic experimental mice,the cardiomyocyte diameter was obviously increased,cell density was decreased,the capillary density was decreased,the intercellular substance was increased,and the intercellular space was increased.Western blot showed that the expression of GRP78,p-JNK and CaMKII in the experimental group of adult APPswe / PS1dE9 transgenic mice were significantly higher than those in the transgenic control mice and WT mice (P＜0.05,P＜0.01).There were no significant difference among the control group oftransgenic mice and the two groups of WT mice.Immunohistochemistry showed that the positive rates of GRP78 and CaMKII in the cytoplasm of cardiomyocytes of the APPswe/PS1 dE9 transgenic experimental mice were significantly higher than those of experimental WT mice (80％&40 ％)(P＜0.05),and the expressions in the two control groups were negative.The positive rates of p-JNK and JNK in the APPswe/PS1dE9 transgenic experimental mice were 90％ and 40％ respectively,and the expressions were negative in other three groups.Conclusions:The adult APPswe/PSldE9 transgenic mice are more prone to cardiac hypertrophy than WT mice after the induction with a low dose of ISO.ER stress is involved in the formation of cardiac hypertrophy in adult APPswe/PS1dE9 transgenic mice.

Objective:To evaluate the diagnostic values of single and combined detection of serum CA199, complement 3 (C3),complement 4 (C4),total cholesterol (TC),triglyceride (TG),and lipid metabolism levels in the patients with pancreatic cancer, and to explore their correlations with TNM stage and pathological stage of pancreatic cancer.Methods:Total 185 subjects were enrolled into the study by three groups:pancreatic cancer patients group (Pc group,n=77),non-digestive system cancer patients group (Ndc group,n=58)and healthy control group (Hc group,n=50).The levels of serum CA199,C3,C4,and high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB), apolipoprotein E (ApoE),and lipoprotein a (Lpa)levels were detected.Results:① The serum level of CA199, C3,C4,and ApoE of the patients in Pc group were higher than those in Ndc and Hc groups (P<0.01).No statistical difference was observed in the serum CA199 between Ndc and Hc groups (P>0.05).The levels of C3, C4,and ApoE in Pc group and Ndc group was higher than those in Hc group (P<0.01),and the levels of the biomarkers in Pc group were also higher than those in Ndc group (P<0.01).The levels of HDL-C,ApoA and Lp (a)of the patients in Pc group were significantly lower than those in Ndc and Hc groups (P<0.05).② The area under ROC curve (AUC)of serum CA199,C3,C4,ApoE,HDL-C,and ApoA were 0.916,0.841, 0.788,0.785,0.834,and 0.810,respectively.Furthermore,multiple factor analysis showed that the combined detection of CA199,C3,and HDL-C (AUC=0.968)improved the diagnosis compared with detecting CA199 alone (P<0.05).③ The CA199 level of the patients inⅢ-Ⅳ stage of TNM stage was higher than that in the patients inⅠ-Ⅱ stage (P<0.01).For the pathological stage,the ApoA level in low differentiation group was higher than that in moderate and high differentiation group (P<0.05).There was no statistical difference in other biomarkers between the different TNM stages and pathological stages.Conclusion:The levels of CA199,C3,C4 and ApoE of pancreatic cancer patients are significantly increased, while the levels of HDL-C, ApoA, and Lp (a ) are significantly reduced.Combined detection of CA199,C3,and HDL-C can improve the early diagnosis of pancreatic cancer compared with the single assessment of each biomarker.