This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

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.

JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis offers a new perspective on the definition, classification, epidemiology, pathophysiology, diagnosis, diagnostic, treatment and management of myocarditis. It also provides recommendations to clinicians on the diagnosis and treatment of myocarditis which are more suitable for clinical practice. Given that no myocarditis guidance document has recently been issued in China, this article provides a comprehensive interpretation of the key points of this guideline combined with the latest research, so as to provide reference for the diagnosis and treatment of myocarditis in our country.

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 explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature. METHODS: Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software. RESULTS: The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4). CONCLUSION The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.
Alkaline Phosphatase ; Child ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypophosphatasia/genetics* ; Mutation ; Whole Exome Sequencing

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