BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Objective:To investigate the gastrointestinal characteristics of children with glycogen storage disease (GSD) type Ⅰ.Methods:From June to December 2020, clinical data of children aged 0-18 years with GSD type Ⅰ diagnosed by genetic testing from all provinces and cities in China, including Beijing, Shanghai, Guangdong, Guangxi, Hunan, Sichuan, Yunnan, Guizhou, Henan, Hebei, Zhejiang, Jiangsu, Shaanxi, Anhui and Heilongjiang, were collected.A cross-sectional questionnaire survey was used for data analysis.Results:A total of 52 questionnaires were obtained, and 43 eligible patients aged 1-18 years were recruited, involving 30 males (69.8%) and 13 females (30.2%). Among them, 9 patients were GSD type Ⅰa and 34 patients were type Ⅰb.Seven patients (16.3%) had siblings who were also diagnosed as GSD type Ⅰb.The gastrointestinal manifestations included recurrent diarrhea in 26 patients (60.5%), perianal lesions (erythema, ulcer, abscess) in 25 patients (58.1%), abdominal pain/distension in 24 patients (55.8%), nausea/vomiting in 22 patients (51.1%), mucus/bloody stool in 14 patients (32.6%). Thirty-three patients (76.7%) had recurrent stomatitis and oral ulcer, and 38 patients (88.0%) had at least two gastrointestinal symptoms.White blood cell (WBC) count was <4.0×10 9/L in 24 patients (55.8%), and absolute neutrophils count was <1.5×10 9/L in 19 patients (44.2%), which was <0.5×10 9/L in 10 patients (23.3%). WBC count and absolute neutrophils count both decreased in children with GSD type Ⅰb.Platelets were >300×10 9/L in 30 patients (69.8%). Eighteen patients with GSD type Ⅰb underwent gastroscopy and colonoscopy, and 16 patients were diagnosed with GSD-related inflammatory bowel disease.Thirty-nine patients (90.7%) were fed with raw corn starch, 3 patients (6.9%) with maltodextrin and 19 patients (44.2%) with special enteral formula.Twenty patients with type Ⅰb GSD needed repeated antibiotic treatment due to neutropenia and neutrophil dysfunction.Fifteen patients were treated with granulocyte colony-stimulating factor (G-CSF). Among them, 11 patients were diagnosed as GSD-related bowel disease. Conclusions:Children with GSD type Ⅰ commonly have gastrointestinal symptoms, especially those with GSD type Ⅰb.The incidence of GSD-related inflammatory bowel disease is high in those children.G-CSF treatment cannot prevent the development of GSD-associated inflammatory bowel disease and its pathogenesis needs further research.Diet therapy is the first-line treatment of GSD type Ⅰ.Multidisciplinary management is helpful to reduce the complications and improve the quality of life in children with GSD type Ⅰ.

Purpose: The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow’s milk protein allergy (CMPA) and lactose intolerance (LI) in infants. Methods: A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) diseasespecific knowledge and potential educational needs. Results: Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/ gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area. Conclusion The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

Objective:To discover the epidemiological characteristics and clinical manifestations of Nontyphoidal Salmonella(NTS) infection in children suffering from diarrhea in Guangzhou, and to provide references for the prevention and treatment of salmonella infection. Methods:A total of 570 diarrhea children and 296 non-diarrhea controls were collected with stratified sampling from three districts of Guangzhou Women and Children′s Medical Center from January 2019 to December 2019. Through bacterial culture, corresponding colonies were selected and Salmonella diagnostic serum was applied for preliminary serum diagnosis, and then systemic biochemical method was adopted for diagnosis. A structured questionnaire was conducted to record the demographic information and clinical symptoms from each subject. Results:The detection rate of NTS was 6.67% (38/570 cases, 95% CI: 4.90%-9.02%) in children with diarrhea, and 1.01% (3/296 cases, 95% CI: 0.34%-2.93%) in children without diarrhea. There were statistically differences in NTS detection rate between children with diarrhea and the control ( χ2=13.805, P<0.05, OR=6.976, 95% CI: 2.135-22.796). There were no significant differences in NTS detection rate between male and female children with diarrhea ( χ2=0.395, P>0.05, OR=1.254, 95% CI: 0.619-2.541). The detection rate of NTS was 5.30% (22/416 cases, 95% CI: 3.52%-7.88%) in children younger than 2 years old, and was 10.40% (16/154 cases, 95% CI: 6.50%-15.21%) in children over 2 years old. There were statistically differences ( χ2=4.700, P<0.05, OR=2.076, 95% CI: 1.060-4.068) between the younger and the older groups.The detection rate of NTS was 5.40% (25/460 cases, 95% CI: 3.70%-7.89%) for children with diarrhea in outpatient department and 11.80% (13/110 cases, 95% CI: 7.04 %-19.18%) for children with diarrhea in inpatient department, with statistically significant differences ( χ2=5.813, P<0.05, OR=2.332, 95% CI: 1.152-4.721). The detection rate of NTS diarrhea in children was 4.60% (10/217 cases, 95% CI: 2.52%-8.28%) in spring, 8.50% (12/141 cases, 95% CI: 4.93%-14.29%) in summer, 9.60% (15/144 cases, 95% CI: 6.41%-16.48%) in autumn and 1.50% (1/168 cases, 95% CI: 0.11%-3.30%) in winter, respectively, with statistically differences among the four seasons( χ2=9.404, P<0.05). There were significant differences in most common clinical symptoms of fever, vomiting, abdominal pain, bloody stool and pasty stool between NTS positive and negative children(all P<0.05). Salmonella enteritis is the main type, and Salmonella typhimurium is the second type. Conclusions:NTS is one of the most important bacterial pathogens and leads to diarrhea in children in Guangzhou city, without differences in gender.Children over 2 years old are more likely to suffer from NTS infection.High incidence is in autumn.The most common clinical symptoms include fever, vomiting, abdominal pain, bloody stool and pasty stool. Salmonella enteritis is the main type, and Salmonella typhimurium is the second type.Laboratory tests can provide references for the diagnosis and treatment of NTS-related diarrhea.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

Nutritional therapy is very important for critically ill children. Most children need to put nasogastric tube for enteral nutrition. Severe esophageal stricture, gastric compression, gastric retention and gastric outlet obstruction may require endoscopic catheterization; dysphagia caused by various reasons, or children who need long￣term catheterization for enteral nutrition,need percutaneous endoscopic gastrointesti￣nal stoma catheterization. Gastroscopy￣guided intubation is divided into nasal intubation of gastric tube,nasal intubation of jejunum tube and nasal intubation of three￣chamber gastrointestinal tube. Percutaneous endoscopic gastrointestinal stoma catheterization can be performed through gastrostomy,jejunostomy and duodenostomy. Choosing suitable catheterization method can help all kinds of critically ill children to establish enteral nutri￣tion pathway as soon as possible and promote recovery of illness.

Enteral nutrition (EN) is the preferred method of clinical nutrition treatment for children.Different EN preparations and feeding methods were chosen according to the age and condition of the children.Breast milk is the best food for infants.For infants with intractable diarrhea after infection,using breast milk as enteral nutrition preparation can promote the recovery of the disease.Total enteral nutrition can be used as the preferred induction therapy for children with Crohn's disease.Individualized diets simulating the nutritional components of enteral nutrition preparations are also being studied.Early EN is not only safe for children with acute pancreatitis,but also can better reduce pain and shorten the average length of hospital stay.Gastrostomy can be considered in children with neurological impairment who need long-term EN.Early EN has been shown to reduce complications,hospital stay and improve prognosis in critically ill children.

Objective To predict and verify the upstream regulatory microRNA (miRNA)of protein kinase D1 (PKD1),and to investigate its role in cerulein induced acute pancreatitis (AP)in rats. Methods Potential up-stream regulatory miRNA of PKD1 was predicted by using bioinformatics software. Dual luciferase reporter gene system and Western blot were applied to verify the regulation of PKD1 by the selected miRNA. Experimental AP was induced by 6 intraperitoneal injection of cerulein (20 μg/ kg)at hourly intervals after administration of the CY5 - labeled notar-get control (AP group,n = 20)or selected miRNA (treatment group,n = 20),respectively by intraperitoneal injection into rats. Other rats were divided randomly into a normal control group (n = 10)without any treatment. Besides 10 rats in either AP or treatment group were sacrificed 6 hours after the first injection of cerulein,and the rats were all sacri-ficed 24 hours after the first injection. The blood samples and pancreatic tissues of each rat were collected to test serum amylase and lipase activities,or to make hematoxylin - eosin stain for AP pathological scores as well as PKD1 immuno-histochemical staining,respectively. Results TargetScan 7. 1 software analysis showed that miR - 128 - 3p was the po-tential upstream regulatory miRNA of PKD1,which was verified by dual luciferase reporter gene system and Western blot detection. Compared to the normal control group,serum amylase and lipase activities after 6 h exposure to cerulein increased in both AP group and the treatment group[13313. 00(9424. 00 - 15995. 00)U/ L,13552. 00(10399. 50 -18408. 25)U/ L vs. 1430. 50(1214. 25 - 1543. 25)U/ L;547. 00 (515. 00 - 627. 00)U/ L,857. 50(522. 00 -1222. 25)U/ L vs. 34. 00(32. 50 - 34. 75)U/ L],and the differences were significant(χ2 = 8. 715,P < 0. 05;χ2 =9. 115,P < 0. 05),which indicated that the rat models of AP were successfully established. The immunohistochemical scores of PKD1 after 24 h exposure to cerulein decreased in the treatment group[0. 50(0 - 2. 75)scores],compared with the normal control group [4. 00(4. 00 - 8. 00)scores]and the AP group [4. 00(3. 75 - 8. 00)scores],and difference was significant(χ2 = 18. 302,P < 0. 05). Accordingly,the total pathological scores of HE staining decreased significantly in the treatment group,as compared to the AP group (3. 80 ± 0. 85 vs. 6. 90 ± 1. 15,t = 4. 481,P < 0. 01). The results showed that the inflammatory cell infiltration and tissue necrosis were significantly improved after miR -128 - 3p treatment. Conclusions miR - 128 - 3p is the upstream regulatory microRNA of PKD1 which protects pan-creata from necrotic injury and inflammatory cell infiltration in PKD1 - mediated acute pancreatitis.

Objective To understand the clinical characteristics of children′s digestive tract deep fungal infection,avoid clinical misdiagnosis and missed diagnosis. Methods We analyzed the clinical characteristics and treatment effect in the children who were diagnosed with gastrointestinal tract deep fungus infection from January 2005 to May 2016 in guangzhou women and children′s hospital. Results Digestive tract deep fungal in-fection in 6 cases. All children are fungal esophagitis,fungal gastrointestinal diseases in 2 cases. The main clinical feature is vomiting,dysphagia and abdominal pain which lasted 4 ~12 weeks. Broad-spectrum antibiotics in 1 case,congenital immunodeficiency in 1 case,congenital esophageal atresia in 3 case. Gastroscopy found clusters of gray spots or jerry-built attachments (3 cases),Esophageal the week covered by gray jerry-built content, scope of 1/3-1/2 esophageal length,with esophageal lumen jams in 3 case. Large superficial ulcer in 2 cases. Le-sions involving the stomach and duodenum in 2 cases,one of which lesions involving the whole digestive gut. 6 cases by mucosa pathological examination or secretions smears identified as candida albicans infection. 3 cases of children with mild choose doxycycline tablets,treatment 2-3 weeks. 3 cases of children with severity choose Itra-conazole Capsules,treatment 3-4 weeks. Gastroscope review the digestive gut which was better than before. But 1 case was diagnosed immunodeficiency disease,death from lung infection. 1 case of whole digestive tract infec-tion,relapse after 3 month,at present is still in follow-up. Conclusion Children′s digestive tract of deep fungal infection is mainly characterized by vomiting,dysphagia and abdominal pain. Fungal can invade the whole diges-tive tract. Esophageal mucosa injury may be one of causes,and at the same time should pay attention to rule out congenital immunodeficiency. Diagnosis is dependent on the digestive endoscopy,mucosal biopsy.

Objective To develop the optimal simplified combination of joints for ultrasonographic assessment of joint inflammation of wrists and hands in patients with rheumatoid arthritis (RA).Methods US examination was performed using grey-scale (GSUS) and power Dop.pler (PDUS) semi-quantitative scoring systems with scores 0-3 in 22 joints of 705 RA patients,including all proximal interphalangeal (PIP),metacarpophalangeal (MCP),and bilateral wrist joints.Continuous variables were presented as mean and standard deviation if normally distributed,and dichotomous variables were presented as frequencies.T test and Wilcoxon signed test were applied for statistical analysis.All correlations among US variables were assessed using Spearman's rank correlation test.Candidate joint set was selected by multiple stepwise linear regression analysis.Results Through multiple linear stepwise regression analysis,the standard coefficient of wrist,MCP5,MCP2 and MCP3 joints under GSUS was higher than other joints.And the adjusted R2 of the model composed of wrist,MCP5,MCP2 and MCP3 joints was greater than 0.9.Among the sum GS and PD scores of various selected joint combinations,total score-8 (GS vs PD),including bilateral wrist,MCP2,MCP3,MCP5 joints,not only showed highest sensitivity and negative predictive value (97.3 5％ vs 97.20％;92.67％ vs 97.21％,respectively),but also had the highest correlation with the total score-22 (GS,PD) (r=0.989,0.972,P＜0.01).Conclusion Total score-8,including bilateral wrist,MCP2,MCP3,MCP5 joints,is simple and efficient enough for monitoring active synovitis of wrists and hands in patients with RA in daily practice.