OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). METHODS: Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. RESULTS: The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. CONCLUSION The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.
Humans ; Child ; Mutation ; Autoimmune Diseases of the Nervous System/genetics* ; Nervous System Malformations/genetics*

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Chronic obstructive pulmonary disease （COPD） is a chronic heterogeneous airway disease characterized by persistent and progressive airflow restriction， which can be divided into stable COPD and acute exacerbations of COPD （AECOPD）. Its morbidity and mortality remain high， posing a serious threat to human health. Traditional Chinese Medicine （TCM） believes that COPD belongs to the categories of "cough"， "dyspnea syndrome"， "lung distension"， etc. And its basic pathogenesis is intermingled phlegm and stasis with deficiency in origin and excess in superficiality. Qianjin Weijingtang， derived from the Records of Proved Prescriptions， Ancient and Modern （古今录验方）， consists of Phragmitis Caulis， Persicae Semen， Coicis Semen， and Benincasae Semen， with remarkable functions in clearing the lung， resolving phlegm and eliminating blood stasis， and has definite clinical efficacy in treating COPD and its syndromes. At present， in clinical studies， Qianjin Weijingtang has been used to treat COPD with modifications. It can be used alone or in combination with other prescriptions/western medicines to treat stable COPD， AECOPD， COPD complications， and other TCM syndromes of COPD such as phlegm-heat-stagnation obstructing the lung syndrome. It can significantly improve clinical symptoms， lung function， and blood gas indexes， and inhibit inflammatory response. Animal experiments mainly explored the mechanism of COPD from the level of pathological changes. Specifically， the underlying mechanism may be related to regulating T helper 17 （Th17）/regulatory T cells （Treg） balance， up-regulating single immunoglobulin IL-1-related receptor （SIGIRR） for resisting inflammation， up-regulating hyperplasia suppressor gene （HSG） and inhibiting Wnt signaling pathway activation to inhibit airway remodeling. It was found that there were many problems， such as low quality of clinical research， failure in sharing research standards， and the lack of mechanism research. This article systematically reviewed clinical studies of Qianjin Weijingtang in the treatment of COPD and its mechanism based on animal experiments in recent years， and put forward thoughts and suggestions according to the existing problems to provide references for the clinical application and further research on Qianjin Weijingtang.

Objective To study the action and mechanism of Sancai Lianmei Particle on cell apoptosis of liver cells in Type 2 Diabetes Mellitus(T2DM)combined with Non-alcoholic Fatty Liver Disease(NAFLD).Methods High fat and sugar + STZ induced diabetic with fatty liver rats used as models,intervention with Sancai Lianmei Particle,intraperitoneal glucose tolerance test(IPGTT)to assess insulin resistance,ELISA method to detect the mice serum biochemistry,insulin levels;ELISA method to detect inflammatory factors in liver homogenate;SOD and MDA levels were monitored to assess the degree of oxidative stress;ASK1/JNK/NF-κB mRNA expression in liver tissue was monitored by Real-time PCR;apoptotic-related proteins were detected by Western blot,apoptosis of hepatocytes was assayed by TUNEL;HE staining was conducted to observe the liver tissue.Results Sancai Lianmei Particle can obviously reduce the body weight of T2DM with NAFLD model rats;reduce the levels of GHb,INS,TC,TG,LDL-C,ALT,AST,IL-1β,IL-6,TNF-α,MDA;improve insulin resistance and oxidative stress.HE staining of liver tissue showed that Sancai Lianmei Particle could alleviate the vacuolar degeneration of liver and deposition of lipid droplets.Sancai Lianmei Particle can effectively down-regulate the expressions of ASK1,JNK and NF-κB mRNA in liver tissues of model rats.Western Blot results exhibited that Sancai Lianmei Particle could significantly regulate the expression of apoptotic proteins of Bax,Caspase-3,and Bcl-2 and inhibit the apoptosis of hepatocytes.Conclusion This study proved that Sancai Lianmei Particle can improve hepatic insulin resistance and oxidative stress,slow the progression of NAFLD by regulating liver cell apoptosis based on ROS-ASK1-JNK/NF-κB pathway.

Objective     To evaluate the effect of mediastinal drainage tube placed in the left thoracic cavity after partial resection of the mediastinum pleura in robot-assisted McKeown esophagectomy for esophageal carcinoma, and to compare it with the traditional method of mediastinal drainage tube placed in mediastinum. Methods    We retrospectively analyzed clinical data of 96 patients who underwent robot-assisted McKeown esophagectomy for esophageal carcinoma by the surgeons in the same medical group in our department between July 2018 and March 2021. There were 78 males and 18 females, aged 52-79 years. Left mediastinum pleura around the carcinoma during operation was resected in all patients. Patients were divided into two groups according to the method of mediastinal drainage tube placement: a control group (placed in mediastinum) and an observation group (placed through the mediastinal pleura into the left thoracic cavity with several side ports distributed in the mediastinum). The incidence of left thoracentesis or catheterization after surgery, anastomotic fistula and anastomotic healing time, other complications such as pneumonia and postoperative pain score were also compared between the two groups. Results     There was no statistical difference in baseline data or surgical parameters between the two groups. The percentage of patients in the observation group who needed re-thoracentesis or re-catheterization postoperatively due to massive pleural effusion in the left thoracic cavity was significantly lower than that in the control group (5.6% vs. 21.4%, P=0.020). The incidence of anastomotic leakage (3.7%vs. 7.1%, P=0.651) and the healing time of anastomosis (18.56±4.27 d vs. 24.33±5.48 d, P=0.304) were not statistically different between the two groups, and there was no statistical difference in other complications such as pulmonary infection. Moreover, the postoperative pain score was also similar between the two groups. Conclusion     For patients whose mediastinal pleura is removed partially during robot-assisted McKeown esophagectomy for esophageal carcinoma, placing the drainage tube through the mediastinal pleura into the left thoracic cavity can reduce the risk of left-side thoracentesis or catheterization, which may promote the postoperative recovery of patients.

Objective:To explore the effect of family integrated care (FIC) combined with intelligent health education platform in health education for elderly patients with stroke.Methods:Eighty patients with stroke were included from the Department of Neurology of the Second Affiliated Hospital of Chongqing Medical University from June 2019 to May 2020. They were divided into the experimental group and the control group ( n=40, respectively) by the random number table method. Patients in the control group received routine FIC in the Department of Neurology. Additional intelligent health education platform was provided for the experimental group to carry out intensive education. The modified Barthel index scale, self-care compliance scale and hospital anxiety and depression scale (HADS) were used before and after the intervention to evaluate patient′s self-care ability, self-care compliance and the degree of anxiety and depression. Results:Finally, 39 patients in the experimental group (1 case lost to followed-up) and 37 patients in the control group (3 cases lost to followed-up) completed the study. After the intervention, the scores of the modified Barthel index and self-care compliance scale of the experimental group were significantly higher than those of the control group [(65.9±12.6) vs (60.1±11.9) points, (78.2±13.6) vs (71.4±14.6) points], the HADS score was significantly lower than the control group [(15.18±2.46) vs (19.46±2.40) points] (all P<0.05). The scores of the modified Barthel index scale and self-care compliance scale of the experimental group after the intervention were significantly higher than those before the intervention [(65.9±12.6) vs (40.8±12.5) points, (78.2±13.6) vs (54.6±15.9) points] (all P<0.05), the HADS score was significantly lower than before the intervention [(15.18±2.46) vs (21.74±3.52) points] (all P<0.05). Similarly,the scores of the modified Barthel index and self-care compliance scale of the control group after the intervention were significantly higher than before the intervention [(60.1±11.9) vs (41.6±9.72) points, (71.4±14.6) vs (54.3±14.8) points], the HADS score was significantly lower than before the intervention [(19.46±2.40) vs (21.38±3.09) points] (all P<0.05). Conclusion:FIC combined with intelligent health education platform can significantly improve the self-care ability and self-nursing compliance of elderly stroke patients, and markedly improve the degree of depression and anxiety.

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Objective To summarize the computed tomography (CT) and magnetic resonance imaging (MRI) features of IgG4-related pancreatitis.Methods The retrospective and descriptive study was conducted.The clinical data of 23 patients with IgG4-associated pancreatitis who were admitted to Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from November 2012 to May 2018 were collected.There were 21 males and 2 females,aged from 45 to 83 years,with an average age of 63 years.Patients underwent upper abdominal enhanced CT and enhanced MRI examinations.Observation indicators:(1) imaging examination of the patients;(2) imaging characteristics on CT and MRI examinations;(3) follow-up.Follow-up using outpatient examination including laboratory and imaging examination was performed to detect clinical symptoms and signs once a month within 3 months postoperatively,once every 3 months within 3 months to 1 year postoperatively,once every 6 months with 1-2 years postoperatively,and once a year after 2 years postoperatively up to August 2018.Measurement data with skewed distribution were represented as M (range).Count data were described as absolute numbers.Results (1) Imaging examination of the patients:19 of 23 patients underwent upper abdominal enhanced CT combined with upper abdominal enhanced MRI scanning,3 underwent upper abdominal enhanced CT combined with upper abdominal MRI plain scanning,and 1 underwent only upper abdominal enhanced MRI scanning.(2) Imaging characteristics on CT and MRI examinations:pancreatic manifestations included 7 aspects.① Location of lesion and morphological classification:of 23 patients,17 were diffuse type,showing sausage-like appearance;4 were focal type,including 2 with mass in the pancreatic head and 2 with mass in the pancreatic body and tail;2 were multiple type,including 1 with mass in the pancreatic head,body and tail,and 1 with mass in the pancreatic body and tail.② Density of lesions on CT examination:of 23 patients,22 received CT plain scanning,including 10 with equal density and 12 with slightly low density;1 didn't receive CT plain scanning.③ Signal of lesions on MRI examination:on T1 weighted imaging,16 of 23 patients showed homogeneous slightly low signal,4 showed isointensity signal,2 showed mixed slightly low signal,and 1 showed slightly high signal.On T2 weighted imaging,21 of 23 patients showed homogeneous slightly high signal,1 showed isointensity signal,and 1 showed mixed slightly high signal.Of 23 patients,19 underwent diffuse weighted imaging (DWI) and 4 didn't undergo DWI.There were 17 patients with slightly high signal and 2 with high signal on DWI.On apparent diffusion coefficient imaging,10 patients showed slightly low signal,and 9 showed low signal intensity.④ Calcification:of 23 patients,2 had multiple calcifications including 1 of diffuse type with calcification located at pancreatic head,and 1 of focal type with calcification located at pancreatic body and tail;20 had no calcification;1 without CT plain scanning cannot be judged calcification.⑤ Enhancement pattern:23 patients showed progressive delayed enhancement of pancreatic lesions on enhancement scanning,homogeneous or heterogeneous enhancement in the arterial phase,and further enhancement in the portal venous phase and delayed phase (enhancement degree of focal type and multiple type was basically consistent with that of normal pancreas).⑥ Halo sign surrounding lesions:of 23 patients,7 had no halo sign,including 2 of diffuse type,3 of focal type,and 2 of multiple type;16 had halo sign (15 of diffuse type and 1 of focal type),including 11 with halo sign surrounding pancreatic body and tail,3 with halo sign surrounding whole pancreas,and 1 with halo sign posterior pancreatic body and tail,and 1 with halo sign anterior pancreatic head.⑦ The main pancreatic duct:14 of 23 patients had irregular stenosis of the main pancreatic duct,7 had mild dilatation of the main pancreatic duct,and 2 had no dilatation of the main pancreatic duct.Extra-pancreatic manifestations included 3 aspects.① Bile duct dilatation:10 of 23 patients had simple intra-hepatic and extra-hepatic bile duct dilatation,8 had no intrahepatic or extra-hepatic bile duct dilatation,and 5 had intra-pancreatic common duct stenosis with upstream bile duct dilatation.② Extra-pancreatic organ involvement:18 of 23 patients had extra-pancreatic organ involvement (5 with gall bladder involvement,4 with intra-hepatic and extra-hepatic bile duct and gall bladder involvement,3 with intra-hepatic and extra-hepatic bile duct involvement,1 with lung involvement,1 with spleen involvement,1 with common duct involvement,1 with kidney involvement,1 with lung and intra-hepatic and extra-hepatic bile duct involvement,1 with fibrosis of mesenteric root),and 5 had no extra-pancreatic organ involvement.③ Retroperitoneal lymph nodes:2 of 23 patients had enlarged retroperitoneal lymph nodes,21 had no enlarged retroperitoneal lymph nodes.(3) Follow-up:of 23 patients,19 were followed up for 3-74 months,with a median time of 22 months.Sixteen of 19 patients had various degrees of improvement in clinical symptoms,laboratory and imaging manifestations after standardized hormonotherapy,and 3 had no response to hormonotherapy.Conclusions CT and MRI examinations have important diagnostic value for IgG4-related pancreatitis.The pancreas mainly show diffuse swelling and halo sign surrounding lesions is a typical imaging characteristic.

Objective:To study the expression and regulation of TLR2/4 in mycobacterium tuberculosis heat shock proteins 16. 3 (mycobacterium tuberculosis heat shock proteins 16. 3,MTB Hsp16. 3) effect on mouse bone marrow-derived macrophages in vitro. Methods:Bone marrow cells were isolated from tibia and femurs of BALB/c mice and incubated with GM-CSF,then detected the expression of CD11b and F4/80 with flow cytometry and observed morphology. The M0 macrophages were stimulated with MTB Hsp16. 3 for 0 h,12 h,24 h,36 h,48 h and 72 h. Real-time PCR detected the expression of TLR2/4 in intracellular at different time point. Silencing macrophages cell surface TLR2/4 molecules by siRNA technology which stimulated with MTB Hsp16. 3 for 0 h,12 h,24 h,36 h,48 h and 72 h. Real-time PCR detected the expression of TLR2/4,Ym-1,Fizz1,IL-10,TNF-α,iNOS and TGF-βin intracellular at different time point. Results:Morphology analysis showed that MTB Hsp16. 3 stimulated macrophages were round cells stretching out pseudopodia,whereas MTB Hsp16. 3 stimulated silencing TLR2/4 macrophages had elongated fibroblastoid. Real time PCR detected the expression of TLR2/4 were upregulated after MTB Hsp16. 3 stimulated M0 macrophages. MTB Hsp16. 3 stimulated silencing TLR2/4 macrophages the expression of IL-6, TNF-α, iNOS were upregulated, whereas IL-10, TGF-β, Ym-1 and Fizz1 were downregulated. Conclusion:MTB Hsp16. 3 may stimulated M0 macrophages to M2 macrophages and suppress M1 macrophages through binding with TLR2/4 receptor,which may be involved the progresss of MTB evaded macrophage phagocytosis.

Objective To investigate the clinical characteristics and molecular pathological mechanism of McCune-Albright syndrome ( MAS) in order to provide a guidance for the precision medicine of MAS. Method The clinical data and genetic findings of 41 patients with MAS were analyzed retrospectively. Results (1) MAS girls had the phenotype of peripheral precocious puberty with premature sexual development and high estradiol, low LH and FSH, and the increased volume of uterus and ovary. ( 2 ) In 41 MAS cases, there were 17 cases with GNAS1 gene mutation, and the total positive rate was 41. 5%, of which the classic triad was 66. 7%, two signs 56. 3%, and 12. 5% in only one classic sign. GNAS1 gene mutation was found in 78. 6% of patients with polyostotic fibrous dysplasia of bone, while only 55. 0% in patients with cafe au lait skin spots. Children with precocious puberty and fibrous dysplasia of bone is an important basis for clinical diagnosis of MAS, but cafe au lait skin spots does not seem to be the specifical manifestation of MAS. Conclusion Clinically MAS was lack of typical clinical manifestations, and the most important clinical weight factor for the diagnosis of MAS was peripheral precocious puberty with fibrous dysplasia of bone. GNAS1 gene screening may be helpful to improve the clinical accurate diagnosis of MAS.