Downhill esophageal varices (DEV) is a rare cause of upper gastrointestinal bleeding. It is different from ascending esophageal varices caused by portal hypertension, and caused by obstruction of the superior vena cava. It can be secondary to an indwelling central venous catheter. It is very dangerous when DEV is complicated with upper gastrointestinal bleeding,and there is no unified treatment strategy at present. We report a case of hemodialysis patient with left upper limb swelling for 6 months and intermittent hematemesis for 3 months. Combined with gastroscopy and CT venography, the patient was considered to have DEV rupture and hemorrhage. The patient was discharged after comprehensive treatment including closure of internal arteriovenous fistula, ligation of bleeding points of esophageal varices, recanalization of superior vena cava, and "culprit" vein embolization. There was no recurrence after half a year of follow-up. This case is helpful for clinicians to improve the recognition on this disease and explore the experience of diagnosis and treatment.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

Objective:To observe whether electroacupuncture(EA)can inhibit activation of JAK1/STAT3 signaling pathway and improve pulmonary inflammation in chronic obstructive pulmonary disease(COPD)by increasing expression of SOCS3.Methods:Atotal of 60 mice were randomly divided into normal group,model(COPD)group,COPD+EA group,COPD+si-SOCS3 group,COPD+si-SOCS3 NC group,COPD+si-SOCS3+EA group,with 10 mice in each group.Mice COPD model was replicated by simple cigarette smoking for three months.After modeling,SOCS3 siRNA was administered to lungs of mice in COPD+si-SOCS3 group and COPD+si-SOCS3+EA group,SOCS3 siRNA NC was administered to COPD+si-SOCS3 NC group.24 h after the first SOCS3 siRNA ad-ministration,mice in COPD+EA and COPD+si-SOCS3+EA groups were treated with EA in"Feishu"and"Zusanli",once every other day,30 min/times for 14 days.Lung function of mice in each group was detected;lung pathological changes were observed by HE staining;IL-6,IL-1β and TNF-α levels in mice broncho alveolar lavage fluid were detected by ELISA;protein expressions of SOCS3,JAK1,STAT3,p-JAK1 and p-STAT3 were detected by Western blot;SOCS3,JAK1 and STAT3 mRNA were detected by RT-PCR.Results:Compared with normal group,mice in COPD group showed decreased lung function,thickened alveolar walls,congestion and edema between tissues,significantly increased levels of inflammatory cytokines IL-6,TNF-α and IL-1β,decreased SOCS3 protein expres-sion,p-JAK1/JAK1 and p-STAT3/STAT3 significantly increased,JAK1 and STAT3 mRNA increased,SOCS3 mRNA decreased(P<0.05).Compared with COPD group,the above indexes of COPD+EA group were improved(P<0.05),and the above indexes of COPD+si-SOCS3 group were more serious(P<0.05),and COPD+si-SOCS3+EA group was improved compared with COPD+si-SOCS3 group(P<0.05).Conclusion:EA can inhibit overactivation of JAK1/STAT3 signaling pathway by up-regulating SOCS3 expression,and thus improve pulmonary inflammation in COPD.

Objective:To construct a shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach and to explore its effectiveness.Methods:The first draft of the shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach was constructed through literature review, and two rounds of expert consultation were conducted with 20 experts to determine the final draft of the program with the results of the pretest. A total of 98 patients who underwent endoscopic thyroidectomy by a gasless unilateral axillary approach in the Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from September 2023 to January 2024 were selected for the study using the convenience sampling method. Patients from September to December 2023 were set up as control group and patients from October 2023 to January 2024 were set up as experimental group, with 49 patients in each group. Control group implemented routine nursing, and experimental group received the shoulder and neck functional exercise program developed in this study on the basis of control group. Constant-Murley Score score, occurrence of numbness in the chest wall access area, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire scores in cancer patients were compared between the two groups at one week, one month, and three months post-intervention.Results:In the two rounds of expert consultation, the effective questionnaire recovery rates were 85.00% (17/20) and 94.12% (16/17), and the coefficient of the expert familiarity was 0.938, the coefficient of basis of judgment was 0.891, and the coefficient of authority was 0.915. The coefficients of variation for the importance ratings of the entries in the second round of consultation were 0.096 to 0.190 and Kendall's harmony coefficient was 0.155 ( P<0.01). The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach included three first-level items, five second-level items, and 13 third-level items. At one week post-intervention, the difference in occurrence of numbness in the chest wall access area was statistically significant in both groups ( P<0.05). At one month post-intervention, the differences in shoulder function scores, occurrence of numbness in the chest wall access area, and quality of life scores between the two groups were statistically significant (all P<0.05). At three months post-intervention, the differences in shoulder function scores and quality of life scores between the two groups were statistically significant (all P<0.05) . Conclusions:The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach has certain scientific validity and feasibility, which can improve the shoulder and neck function of patients undergoing endoscopic thyroidectomy by axillary approach, reduce the numbness in the chest wall access area, and improve the quality of life of the patients in the postoperative period.

Objective:To observe whether electroacupuncture(EA)can inhibit activation of JAK1/STAT3 signaling pathway and improve pulmonary inflammation in chronic obstructive pulmonary disease(COPD)by increasing expression of SOCS3.Methods:Atotal of 60 mice were randomly divided into normal group,model(COPD)group,COPD+EA group,COPD+si-SOCS3 group,COPD+si-SOCS3 NC group,COPD+si-SOCS3+EA group,with 10 mice in each group.Mice COPD model was replicated by simple cigarette smoking for three months.After modeling,SOCS3 siRNA was administered to lungs of mice in COPD+si-SOCS3 group and COPD+si-SOCS3+EA group,SOCS3 siRNA NC was administered to COPD+si-SOCS3 NC group.24 h after the first SOCS3 siRNA ad-ministration,mice in COPD+EA and COPD+si-SOCS3+EA groups were treated with EA in"Feishu"and"Zusanli",once every other day,30 min/times for 14 days.Lung function of mice in each group was detected;lung pathological changes were observed by HE staining;IL-6,IL-1β and TNF-α levels in mice broncho alveolar lavage fluid were detected by ELISA;protein expressions of SOCS3,JAK1,STAT3,p-JAK1 and p-STAT3 were detected by Western blot;SOCS3,JAK1 and STAT3 mRNA were detected by RT-PCR.Results:Compared with normal group,mice in COPD group showed decreased lung function,thickened alveolar walls,congestion and edema between tissues,significantly increased levels of inflammatory cytokines IL-6,TNF-α and IL-1β,decreased SOCS3 protein expres-sion,p-JAK1/JAK1 and p-STAT3/STAT3 significantly increased,JAK1 and STAT3 mRNA increased,SOCS3 mRNA decreased(P<0.05).Compared with COPD group,the above indexes of COPD+EA group were improved(P<0.05),and the above indexes of COPD+si-SOCS3 group were more serious(P<0.05),and COPD+si-SOCS3+EA group was improved compared with COPD+si-SOCS3 group(P<0.05).Conclusion:EA can inhibit overactivation of JAK1/STAT3 signaling pathway by up-regulating SOCS3 expression,and thus improve pulmonary inflammation in COPD.

Objective:To construct a shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach and to explore its effectiveness.Methods:The first draft of the shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach was constructed through literature review, and two rounds of expert consultation were conducted with 20 experts to determine the final draft of the program with the results of the pretest. A total of 98 patients who underwent endoscopic thyroidectomy by a gasless unilateral axillary approach in the Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from September 2023 to January 2024 were selected for the study using the convenience sampling method. Patients from September to December 2023 were set up as control group and patients from October 2023 to January 2024 were set up as experimental group, with 49 patients in each group. Control group implemented routine nursing, and experimental group received the shoulder and neck functional exercise program developed in this study on the basis of control group. Constant-Murley Score score, occurrence of numbness in the chest wall access area, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire scores in cancer patients were compared between the two groups at one week, one month, and three months post-intervention.Results:In the two rounds of expert consultation, the effective questionnaire recovery rates were 85.00% (17/20) and 94.12% (16/17), and the coefficient of the expert familiarity was 0.938, the coefficient of basis of judgment was 0.891, and the coefficient of authority was 0.915. The coefficients of variation for the importance ratings of the entries in the second round of consultation were 0.096 to 0.190 and Kendall's harmony coefficient was 0.155 ( P<0.01). The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach included three first-level items, five second-level items, and 13 third-level items. At one week post-intervention, the difference in occurrence of numbness in the chest wall access area was statistically significant in both groups ( P<0.05). At one month post-intervention, the differences in shoulder function scores, occurrence of numbness in the chest wall access area, and quality of life scores between the two groups were statistically significant (all P<0.05). At three months post-intervention, the differences in shoulder function scores and quality of life scores between the two groups were statistically significant (all P<0.05) . Conclusions:The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach has certain scientific validity and feasibility, which can improve the shoulder and neck function of patients undergoing endoscopic thyroidectomy by axillary approach, reduce the numbness in the chest wall access area, and improve the quality of life of the patients in the postoperative period.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

Downhill esophageal varices (DEV) is a rare cause of upper gastrointestinal bleeding. It is different from ascending esophageal varices caused by portal hypertension, and caused by obstruction of the superior vena cava. It can be secondary to an indwelling central venous catheter. It is very dangerous when DEV is complicated with upper gastrointestinal bleeding,and there is no unified treatment strategy at present. We report a case of hemodialysis patient with left upper limb swelling for 6 months and intermittent hematemesis for 3 months. Combined with gastroscopy and CT venography, the patient was considered to have DEV rupture and hemorrhage. The patient was discharged after comprehensive treatment including closure of internal arteriovenous fistula, ligation of bleeding points of esophageal varices, recanalization of superior vena cava, and "culprit" vein embolization. There was no recurrence after half a year of follow-up. This case is helpful for clinicians to improve the recognition on this disease and explore the experience of diagnosis and treatment.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.