ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

Dachengqi Decoction is a classic prescription attacked by Yangming excessive syndromes in clinic, which has the effects of relieving heat, softening and dispersing knots, etc., and is often used in the treatment of gastrointestinal dysfunction caused by various diseases. This article reviewed the recent studies on the chemical compositions and pharmacological effects of Dachengqi Decoction in recent years. On this basis, combined with the "five principles" of TCM quality markers, the quality markers of Dachengqi Decoction were predicted and analyzed. It is suggested that emodin, Rhein, chrysophanol, aloe-emodin, synephrine, hesperidin, naringin, magnolol and magnolol can be used as quality markers of Dachengqi Decoction.

OBJECTIVE To explore the potential mechanism of action of Gexia zhuyu decoction in the intervention of metabolic-associated fatty liver disease （MAFLD） based on ferroptosis. METHODS With the help of network pharmacology， the central targets of Gexia zhuyu decoction intervening in ferroptosis of MAFLD were screened， then gene ontology， Kyoto Encyclopedia Gene and Genomes enrichment analysis and molecular docking were performed. Juvenile zebrafish with normal development at 3 d post-fertilization were randomly divided into control group， model group （5 mmol/L thioacetamide）， magnesium isoglycyrrhizinate group （positive control， 5 mg/mL）， and Gexia zhuyu decoction low- ， medium- and high- concentration groups （20， 40， 80 μg/mL， calculated by crude drugs）. After cultured for 72 h， the contents of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， reactive oxygen species （ROS） and Fe2+ were determined； the cellular structure of the liver tissues and hepatic steatosis were observed； the protein expression of silence information regulator 1 （SIRT1）， nuclear factor- erythroid 2-related factor 2 （Nrf2） and glutathione peroxidase 4 （GPX4） were detected. RESULTS The central targets of potential active ingredients of Gexia zhuyu decoction that act on ferroptosis in MAFLD included tumor proteins p53， SIRT1， Nrf2， etc.， which were enriched in biological processes such as positive/negative regulation of RNA polymerase Ⅱ promoter transcription， cellular components such as nucleus and cytoplasm， molecular functions such as protein binding， as well as signaling pathways such as ferroptosis and the cancer pathway， and they might be tightly linked to the main active ingredients. Compared with model group， the contents of ALT， AST， TC， TG， MDA， ROS and Fe2+ were all decreased significantly in each administration group， while the contents of SOD and GSH were increased significantly （P＜0.05）； the pathological damage of liver tissue cells had improved， and the accumulation of liver lipids had decreased. The protein expressions of SIRT1， Nrf2 and GPX4 had been significantly upregulated （P＜0.05）. CONCLUSIONS Gexia zhuyu decoction can regulate lipid metabolism， improve the level of oxidative stress， maintain Fe2+ homeostasis， and inhibit the process of ferroptosis in juvenile zebrafish with MAFLD， and the above effects may be related to the activation of the SIRT1/Nrf2/GPX4 axis.

Objective:To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis.Methods:CHB patients who underwent liver biopsy at Tianjin Second People′s Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t-tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results:The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P<0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group ( P<0.05). In logistic regression analysis MAFLD [odds ratio ( OR)=2.204, 95% confidence interval ( CI) 1.018-4.774, P=0.045], GGT ( OR=1.008, 95% CI 1.002-1.013, P=0.005), and PLT ( OR=0.995, 95% CI 0.991-0.999, P=0.019) were associated with advanced fibrosis (all P<0.05). In the MAFLD-CHB group type 2 diabetes ( OR=3.281, 95% CI 1.375-7.832, P=0.007), GGT ( OR=1.011, 95% CI 1.003-1.018, P=0.005), and PLT ( OR=0.993, 95% CI 0.988-0.998, P=0.004) were associated with advanced fibrosis ( P<0.05). Conclusion:Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective This study aimed to evaluate the influence of ceramic type and thickness on the masking abili-ty and final aesthetic effects of chairside machinable all-ceramic crowns.Methods Six kinds from three types chairside machinable ceramic materials(IPS e.max CAD HT/MT/LT,IPS Empress LT,and VITA Suprinity HT/T)in shade A2 were fabricated to slice specimens into 1.0,1.5,and 2.0 mm-thick sections(n=10).The color parameters of the speci-mens against black and white tiles and four resin substrates(A2,A4,B3,and C4 shade)were measured with a spectro-photometer.The translucency parameter(TP)was calculated using color parameters measured over standard white and black backgrounds.The color differences(ΔE)were cal-culated between there substrate shades(A4,B3,C4)and A2 shade(control group).Two-way analysis of variance(ANOVA)was performed on the TP values.The two va-riables were ceramic type and ceramic thickness.Three-way ANOVA was used to determine the effects of ceramic materials,ceramic thickness,and substrate shades on the ΔE values,followed by Tukey test for multiple comparisons(α=0.05).Results Ceramic type,ceramic thickness,and sub-strate shade significantly affected the ΔE values(P<0.001).The L* and b* values of the specimens increased with in-creasing ceramic thickness,except in substrate A2,whereas the ΔE values decreased.The color difference of all 1.0 mm-thick specimens or all specimens over the substrates C4 shade exceeded the clinically acceptable threshold(ΔE>3.3).Conclusion The masking ability of chairside machinable all-ceramic crowns is influenced by ceramic type and thick-ness,and ceramic material.The thickness of ceramic less than 2.0 mm cannot mask the gray shade abutment.