[Genetic mutation profiles for children with congenital hypothyroidism in Fujian province].

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.

[Precise immunological classification guidance for early initiation of antiviral therapy in patients with chronic HBV infection].

Chronic hepatitis B virus (HBV) infection is a major problem affecting global public health. Appropriate antiviral therapy use can prevent or delay the occurrence of liver cirrhosis and liver cancer. Precise immunological classification can be helpful to formulate personalized therapy and management plans for HBV-infected patients. Antiviral therapy should be started early in those who meet antiviral indications, and nucleos(t)ide analogue therapeutic regimens alone or in combination with pegylated interferon alpha should be optimized according to antiviral therapy response, in order to maximize the realization of virological and serological response, improve clinical cure rate, and enhance long-term prognosis.

[Emphasis on targeted and immunotherapy for liver injury in hepatocellular carcinoma].

Treatment with molecular targeted drugs and immune checkpoint inhibitors (ICIs) has become the first-line treatment options for unresectable HCC (hepatocellular carcinoma) and is also one of the anti-recurrence therapies of choice for patients at high risk of recurrence following radical treatment. First-line molecular targeted drugs combined with ICIs or dual-immune therapy significantly increase the median overall survival and objective response rate compared to single-targeted drugs. Targeted therapy and immunotherapy are suitable for HCC patients with Child-Pugh classes A~B. Liver damage caused by targeted drugs includes abnormal transaminases and bilirubin and, in severe cases, hypoproteinemia, ascites, and other occurrences. ICIs-associated immune-mediated hepatitis (IMH) mostly occurs within one to three sessions of treatment (4~12 weeks) and can be treated with glucocorticoids. However, immunosuppressants such as mycophenolate mofetil may be used as necessary.Targeted drugs and ICIs with different mechanisms of action can be selected based on the systemic condition and tumor treatment needs following the restoration of normal liver function.

[Strategies for liver injury caused by hepatocellular carcinoma targeted therapy].

Primary hepatocellular carcinoma has a high degree of malignancy, insidious onset, and rapid progression that seriously threatens human life and health. With the continuous deepening of the study of the molecular characteristics of tumors, molecular targeted drugs have become an important treatment method for patients with advanced liver cancer. Liver injury is one of the common adverse reactions of targeted drugs, which needs to be paid attention to. This paper mainly briefly expounds on the occurrence condition, mechanism, risk factors, diagnosis, and treatment of liver injury caused by hepatocellular carcinoma targeted therapy in order to provide a reference for the safe clinical application of targeted drugs.

[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma].

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

[Treatment of lumbar degenerative diseases with recapping laminoplasty and nerve root canal's decompression preserving the continuity of supraspinous ligament].

Objective: To explore the clinical effect of lumbar discectomy and nerve root canal's enlargement preserving the continuity of supraspinous ligament in the treatment of lumbar degenerative disease. Methods: The data of patients with lumbar degenerative disease who underwent operation from 2016 to 2018 were analyzed retrospectively, and the patients were divided into two groups according to the different operation. The treatment group (17 cases) was treated with recapping laminoplasty, lumbar discectomy and nerve root canal's enlargement, and the control group (28 cases) was treated with total laminectomy, nerve root canal's enlargement, lumbar discectomy, interbody fusion and internal fixation (PLIF). All patients were followed up for 12 to 27 months (mean 17.8 months). Japanese Orthopaedic Association Scores(JOA) and visual analogue scale(VAS) of pain were used to evaluate the clinical effect before and after the operation, lumbar dynamical X-ray and Cobb angle were collecting for imaging evaluation, and the adjacent segment degeneration at the last follow-up was recorded. Results: There was no significant difference in preoperative JOA score, VAS score and Lumbar Cobb angle between the two groups (all P>0.05). The operation time in the treatment group was shorter than that in the control group, and the blood loss during operation in the treatment group was lower than that in the control group, the bed rest time of the treatment group after operation was shorter than that in the control group ((79±14) vs (118±17) min, (151±38) vs (324±70) ml and (3.4±0.7) vs (4.3±1.0) d,respectively; t=-8.508, -10.724, -3.244, all P<0.01). In addition, compared with the control group, the volume of postoperative drainage in the treatment group also decreased significantly (t=-5.637, P<0.01). There was no significant difference in JOA score between the two groups 1 year after the operation (P>0.05), but there was significant difference in VAS score between the two groups, the treatment group was better than the control group (P<0.05). Compared with the control group, the lumbar Cobb angle in the treatment group increased significantly one year after the operation (55.3°±3.2° vs 38.4°±6.2°, t=10.391, P<0.05). During the follow-up, no loosening or fracture of the implants was found in all patients. Conclusion: Treatment of lumbar degenerative diseases with recapping laminoplasty and nerve root canal's decompression preserving the continuity of supraspinous ligament by ultrasound osteotome has the same clinical effect as PLIF. It has the advantages of shortening operation time, less bleeding, better maintenance of lumbar lordosis after operation and reduction of adjacent segment degeneration.

[Clinical study of yiqi huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis].

Objective: To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis. Methods: An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe (n = 127) and Fuzheng Huayu capsule (n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results: Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them (P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees (P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ​​of both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group (P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion: Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.