Zhigancao Tang （also known as Fumaitang） is a classic formula for treating "intermittent pulse and palpitations" and is widely used in clinical practice. Sanjia Fumaitang， included in the Catalogue of Ancient Classical Formulas （First Batch） published by the National Administration of Traditional Chinese Medicine of China in 2018， is derived from this formula. This paper employed bibliometric methods to comprehensively investigate and summarize the historical evolution， drug composition， herb origins and preparation， prescription meanings， and ancient and modern applications of Zhigancao Tang， analyzed the composition and usage of Zhigancao Tang， and discussed the reasons and applications of the "Fumaitang" variants created by Wu Jutong. A total of 47 valid pieces of data from 38 ancient texts were included. Results showe that Zhigancao Tang originates from the Treatise on Cold Damage （Shang Han Lun）， and the name "Fumaitang" is also recorded in the formula's description. Converted to modern measurements from the Han dynasty system， the recommended preparation for Zhigancao Tang includes 55.2 g of fried Glycyrrhizae Radix et Rhizoma， 41.4 g of Cinnamomi Ramulus， 27.6 g of Ginseng Radix et Rhizoma， 220 g of fresh Rehmannia glutinosa， 27.6 g of Asini Corii Colla， 53 g of Ophiopogonis Radix， 45 g of Cannabis Fructus， and 90 g of Jujubae Fructus. All herbs should be decocted with 1 400 mL of yellow rice wine and 1 600 mL of water until 600 mL. Once the Asini Corii Colla is fully dissolved， the decoction should be taken warm at a dosage of 200 mL， three times a day. Zhigancao Tang is effective for replenishing Qi， warming Yang， nourishing Yin， and nourishing blood and is primarily used to treat “intermittent pulse and palpitations” caused by deficiencies in heart Yin and Yang， as well as malnutrition of the heart meridian and conditions like lung atrophy. Modern applications mainly focus on cardiovascular and cerebrovascular diseases， including arrhythmias， coronary heart disease， and premature ventricular contractions. The findings from this research provide a reference for the further development of Zhigancao Tang.

Objective:To investigate the incidence, influencing factors, and clinical characteristics during hospitalization of small for gestational age (SGA) infants among very preterm infants (VPIs) in neonatal intensive care units (NICUs).Methods:This study was a multicenter cohort study. Clinical data of VPIs with gestational age<32 weeks admitted to 19 collaborative units from January 1, 2019 to December 31, 2022, were collected from the Neonatal Perinatal Collaborative Network of Suxinyun (SNPN) and analyzed. General characteristics, perinatal conditions, and clinical manifestations during hospitalization of SGA infants among the VPIs were analyzed using Chi-square test, Mann-Whitney U test, and multivariate logistic regression. Clinical characteristics of symmetric and asymmetric SGA infants with hospital stay >7 d were also analyzed. Results:(1) During the study period, a total of 5 045 VPIs were included, among which there were 346 large for gestational age (LGA) infants, 4 475 appropriate for gestational age (AGA) infants, and 224 SGA infants, with a SGA incidence of 4.4%. The incidence of SGA was significantly higher in VPIs born at 30-31 +6 gestational weeks than in those with gestational age<28 weeks and born at 28-29 +6 weeks [6.1% (145/2 380) vs. 3.0% (25/833) and 3.6% (54/1 486), χ 2=11.77 and 11.32, both P<0.001]. No significant difference in SGA incidence was found between VPIs with gestational age<28 weeks and those born at 28-29 +6 weeks ( χ 2=0.65, P=0.248). (2) Multivariate logistic regression analysis showed that multiple pregnancies, hypertensive disorders of pregnancy (HDP) and assisted reproductive technology (ART) were independent risk factors for the occurrence of SGA in VPIs [ OR values (95% CI): 1.94 (1.43-2.64), 7.06 (5.34-9.33), and 1.59 (1.14-2.23)], and there was a significant gender difference, with the incidence of SGA being significantly lower in males than in females ( OR=0.61, 95% CI: 0.46-0.81). (3) The body temperature of SGA infants on admission was lower than that of AGA infants [36.0 °C (35.5-36.5 °C) vs. 36.0 °C (35.8-36.5 °C), Z=-2.08, P=0.004]. Moreover, the fasting time, the duration of parenteral nutrition, and the length of hospital stay for SGA infants were longer [3 d (1-7 d) vs. 2 d (1-5 d), 24 d (16-34 d) vs. 19 d (13-29 d), and 47 d (37-61 d) vs. 42 d (30-58 d), Z=-4.13,-4.65, and -3.02, all P<0.05]. The incidence of feeding intolerance, hypoglycemia, neonatal parenteral nutrition-associated cholestasis, and extrauterine growth restriction (EUGR), and the rate of treatment withdrawal or death were also higher in SGA infants [69.8% (143/205) vs. 58.9% (2 450/4 157), 17.6% (36/205) vs. 7.0% (292/4 157), 13.7% (28/205) vs. 6.4% (265/4 157), 77.7% (159/205) vs. 55.2% (2 295/4 157), and 7.8% (16/205) vs. 3.9% (162/4 157), χ 2=9.49, 31.19, 16.54, 44.40, and 7.62, all P<0.05]. Among SGA infants with hospital stay >7 d, there were 111 cases (54.1%) of symmetric SGA and 94 cases (45.9%) of asymmetric SGA. Compared with symmetric SGA infants, asymmetric SGA infants had shorter body length [34 cm (32-36 cm) vs. 38 cm (36-40 cm), Z=-8.49] and lower Apgar score at 1 min [7 points (5-8 points) vs. 8 points (5-8 points), Z=-3.05]. Besides, the proportion of multiple pregnancies and the incidence of postnatal hypoglycemia were higher in asymmetric SGA cases [38.3% (36/94) vs. 21.6% (24/111), 24.5% (23/94) vs. 10.8% (12/111), χ 2=6.84 and 6.71, both P<0.05], while the incidence of feeding intolerance and EUGR during hospitalization was lower [61.7% (58/94) vs. 76.6% (85/111), 58.5% (55/94) vs. 79.3% (88/111), χ2=5.34 and 10.41, both P<0.05]. Conclusions:Multiple pregnancies, HDP, and ART can increase the risk of SGA in VPIs. SGA infants may have increased risks of parenteral nutrition-related problems and EUGR during hospitalization. Symmetric SGA infants are more likely to develop EUGR.

Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

Objective:To study the application of 3D printing technology in multi-center fenestrated/branched endovascular repair (F/B-EVAR) for endovascular repair of abdominal aortic diseases.Methods:From Feb 2018 to Mar 2023, The clinical and followup data of 316 cases of abdominal aortic lesions undergoing repair with F/B-EVAR at 69 medical centers nationwide using 3D printing technology to guide physician-modified stent graft were retrospectively analyzed.Results:The mean follow-up time of the patients was 23 months (2-60 months), and 24 cases were lost to follow up, the follow-up rate was 92.4% (292/316), the mean postoperative hospitalization time was (8.2±4.9) days. A total of 944 main abdominal branch arteries were reconstructed. Intraoperative reconstruction of 11 branches failed, with a success rate of 98.8% (933/944). Within 30 days after surgery, 8 patients died (2.5%), and 6 patients died during follow-up, a total of 14 patients died (4.4%). There were 11 cases (3.5%) of spinal cord ischemia and no patient suffered from permanent paraplegia. There were 19 patients (6.0%) with postoperative renal function injury. Internal leakage was found in 26 patients, and the rate of internal leakage was 8.2%.Conclusion:3D printing technology can accurately locate the location of branch arteries, simplifing the surgical process, shortening the learning curve , and improving clinical efficacy.

Objective:To review the risk factors for early and medium-term complications of fenestration-branch endovascular thoracic aortic repair (F/B-TEVAR) in patients with complex aortic arch disease.Methods:The clinical and follow-up data of 202 patients undergoing F/B-TEVAR treatment from Feb 2019 to Sep 2023 in these centers were retrospectively analyzed .Results:There were 46 cases suffering from postoperative complications (22.8%). The risk factors with statistical significance included aortic atherosclerotic plaque [ OR=2.843; 95% CI (1.4-5.6); P<0.01], aortic intramural thrombosis [ OR=2.358; 95% CI (1.2-4.6), P=0.011], the aortic dilatation [ OR=4.219; 95% CI (1.6-11.3), P<0.01], the history of stroke [ OR=2.088; 95% CI (1.1-4.1), P=0.032], smoking history [ OR=2.680; 95% CI: (1.3-5.5); P<0.01], duration of surgery [ OR=1.9; 95% CI: (1.2-2.9); P=0.042].While the application of 3D printing assistive technology [ OR=0.392; 95% CI: (0.2-0.9); P=0.048] was in a negative correlation with postoperative complication. Conclusions:The independent risk factors for complications after F/B-TVAR included aortic atherosclerotic plaque, aortic intramural thrombosis, the aortic dilatation, the history of stroke, smoking history,duration of surgery.The application of 3D printing technology can effectively reduce the complication rate.

Disturbances of gut microbiota may affect the balance of the host immune system.The metabolism of gut microbiota produces many bioactive molecules interacting with host,typically secondary bile acids(SBAs).SBAs are involved in regulating the energy metabolism and the expression of inflammatory response-related genes by bind-ing to membrane receptors and nuclear receptors,such as takeda G protein-coupled receptor(TGR5)and farnesol X receptor(FXR),which are essential for maintaining host immune homeostasis.

Objective:To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.Methods:A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. The anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c. 258+ 2T>C and c. 100A>G compound heterozygous variants of the SBDS gene. The c. 258+ 2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 100A>G variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). Conclusion:The compound heterozygous variants of c. 258+ 2T>C and c. 100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

OBJECTIVE: To report on the clinical features and result of genetic testing for a child featuring immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Clinical records, genetic testing, laboratory investigation and treatment of the child were summarized in addition with a comprehensive review of the literature. RESULTS: The 3-year-old boy was administered due to intractable diarrhea, recurrent infections, liver dysfunction and failure to thrive, though no diabetes or skin disorder was observed. Laboratory testing showed elevated liver enzymes and total IgE, decreased albumin and electrolyte imbalance. Gastrointestinal endoscopy revealed erosion and granules in the duodenum, and edema in the terminal ileum and colon. Biopsies showed villous atrophy in the duodenum and terminal ileum. Genetic testing revealed that the patient has carried a missense c.1087A>G (p.I363V) variant in the exon 10 of the FOXP3 gene. He was treated with enteral and parenteral nutrition, anti infection and Sirolimus, and was waiting for hemopoietic stem cell transplantation. CONCLUSION Although IPEX syndrome usually occur during infancy, it should not be ruled out solely based on the age, and its presentation can be variable. For male children with refractory diarrhea, autoimmune disorder and growth retardation, the diagnosis should be suspected and confirmed by genetic testing.
Child, Preschool ; Diabetes Mellitus, Type 1/genetics* ; Diarrhea/genetics* ; Forkhead Transcription Factors/genetics* ; Genetic Diseases, X-Linked/genetics* ; Genetic Testing ; Humans ; Immune System Diseases/genetics* ; Male ; Mutation ; Polyendocrinopathies, Autoimmune/genetics*

Objective:To investigate the clinical characteristics, endoscopic features and management of acquired tracheoesophageal fistula (TEF) by esophageal foreign bodies in children.Methods:The clinical data and follow-up data of 21 children with acquired TEF who were treated in Children′s Hospital Affiliated to Zhengzhou University from January 2008 to January 2019 were retrospectively analyzed.Results:A total of 21 cases with esophageal foreign bodies were button batteries, irregular iron sheets, game coins, jujube seed, animal bone sheets, and fish thorn.The statistical results suggested that the cases of button batteries were 7 cases (33.33%), 4 cases of jujube pit (19.05%), 3 cases of irregular iron (14.29%) and 3 cases of animal bone (14.29%), 2 cases of game coin (9.52%), 2 cases of fish thorn (9.52%). All foreign bodies were removed by endoscopy.Esophageal perforation with TEF was discovered in 17 cases (80.95%) during the operation.Esophageal perforation with TEF was found in 4 cases (19.05%) within 2 week after the operation, and no death occurred.A total of 13 case fistula size ≤5 mm (61.90%), 4 case fistula size>5 mm and ≤10 mm (19.05%) and 4 case fistula size >10 mm (19.05%). The treatment methods included gastrointestinal decompression and nasojejunal nutrition tube support in 10 cases (47.61%), gastrostomy and jejunostomy in 4 cases (19.05%), surgical repair in 4 cases (19.05%) and endoscopic titanium clip suture in 3 cases (14.29%). Five cases (23.81%) were healed in 3 months, 6 cases (28.57%) in 5 months, 4 cases (19.05%) in 8 months, and 2 cases (9.52%) in 12 months.Conclusions:Acquired TEF in children are mostly caused by special foreign bodies embedded in the esophagus, and endoscopic management is effective for fistulas with less trauma.Appropriate operation and intervention should be taken as early as possible.