Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

OBJECTIVE: To observe the clinical effect of CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method on post-stroke swallowing dysfunction (PSD) in the pharyngeal phase, and explore its biomechanical mechanism. METHODS: A total of 72 patients with PSD in the pharyngeal phase were randomly divided into a ziwu reinforcing and reducing acupuncture group (36 cases, 2 cases dropped out and 1 case was eliminated) and a conventional acupuncture group (36 cases, 1 case dropped out and 1 case was eliminated). The patients in the conventional acupuncture group were treated with conventional acupuncture at Lianquan (CV 23) and bilateral Fengchi (GB 20), Wangu (GB 12), Tongli (HT 5), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3). The patients in the ziwu reinforcing and reducing acupuncture group were treated with CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method on the basis of the conventional acupuncture group's acupoints. Both groups were treated with acupuncture for 30 min each time, once a day, and rested for 1 day after 6 days of treatment, and the treatment lasted 4 weeks. Before and after treatment, the standardized swallowing assessment (SSA) score, Rosenbek penetration aspiration scale (PAS) grade, the shortening rate of mandibular-hyoid distance, swallowing quality of life (SWAL-QOL) score were evaluated in the two groups. The removal rate of nasogastric feeding tube was compared in the two groups, and the clinical efficacy and safety of the two groups were compared. RESULTS: After treatment, the SSA scores and PAS grade of the two groups were lower than those before treatment (P<0.001), and above indexes in the ziwu reinforcing and reducing acupuncture group were lower than those in the conventional acupuncture group (P<0.01, P<0.05). After treatment, the shortening rates of mandibular-hyoid distance and SWAL-QOL scores in the two groups were higher than those before treatment (P<0.001), and the shortening rate of mandibular-hyoid distance in the ziwu reinforcing and reducing acupuncture group was higher than that in the conventional acupuncture group (P<0.001). The removal rate of nasogastric feeding tube in the ziwu reinforcing and reducing acupuncture group was 87.9% (29/33), which was higher than 61.8% (21/34) in the conventional acupuncture group (P<0.05). The total effective rate of the ziwu reinforcing and reducing acupuncture group was 84.8% (28/33), which was higher than 61.8% (21/34) of the conventional acupuncture group (P<0.05). Neither group experienced serious adverse reactions. CONCLUSION CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method can effectively improve swallowing dysfunction in the pharyngeal phase after stroke, reduce the risk of aspiration, and improve quality of life. Its therapeutic effect may be related to increasing the displacement amplitude of the hyoid bone.
Humans ; Male ; Female ; Middle Aged ; Aged ; Acupuncture Therapy ; Stroke/therapy* ; Acupuncture Points ; Deglutition Disorders/physiopathology* ; Deglutition ; Treatment Outcome ; Adult ; Pharynx/physiopathology*

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To explore the establishment of a Cox proportional hazard prediction model for the re-cent(within a week)delivery of pregnant women with threatened early preterm labor(28-33+6 weeks).Meth-ods:The clinical data of 293 patients with threatened early preterm labor at 28-33+6 weeks admitted to the De-partment of Obstetrics,Affiliated Hospital of North Sichuan Medical College from January 2021 to December 2022 were retrospectively collected.According to whether the patient gave birth recently(within a week)during hospi-talization,they were divided into delivery group(n=88)and non-delivery group(n=205).Demographic data,specialty conditions and clinical biochemical indicators were collected,and the differences of each observation in-dex between the two groups were compared.Cox multivariate analysis was used to screen variables,and then the Cox proportional hazard prediction model was constructed to calculate the hazard ratio(HR).The C-index was used to test the predictive ability of the model,and the nomogram was drawn to visualize the Cox proportional hazard prediction model.The calibration curve was used to test the consistency between the model prediction re-sults and the actual situation.Results:The average age of the delivery group was 30.2±5.0 years old,and the average prolonged pregnancy time was 61.3±47.5 hours.Compared to the group that gave birth and did not give birth,the proportion of patients with body mass index(BMI)at admission,parity＞1,gestational diabetes mellitus or diabetic pregnancy combined(GDM/PGDM),abnormal fetal orientation,regular contractions at admis-sion,vaginal cleanliness≥ Ⅲ,white blood cell count ≥10 ×109/L at admission and cervical length＜20 mm,the difference was statistically significant(P＜0.05).Multivariate Cox regression analysis:BMI＞30 kg/m2(HR 2.178,95％CI 1.208-3.928,P=0.010),parity＞1(HR 3.095,95％CI 1.759-5.447,P＜0.001),regular uterine contraction(HR3.447,95％CI 2.216-5.362,P＜0.001),cervical length＜20 mm(HR3.594,95％CI 2.289-5.646,P＜0.001)and white blood cell count≥10 ×109/L(HR2.124,95％CI 1.352-3.335,P=0.001)on admission were independent risk factors for recent(within a week)delivery of pregnant women with threatened early preterm birth.When the above 5 indicators were included in the prediction model,the C-index was 0.797(95％CI 0.750-0.844),indicating that the model had good prediction ability.The calibration chart shows that the prediction results of the model are in good agreement with the actual results.Conclusions:Preg-nant women with BMI＞30 kg/m2 at admission,parity＞1,regular uterine contraction at admission,cervical length＜20 mm at admission and white blood cell count≥10 ×109/L at admission are prone to premature delivery in the near future.Cox proportional risk prediction model based on the above risk factors has certain accuracy,which can be used to guide clinical workers to take corresponding intervention measures in advance to avoid or reduce the possibility of premature delivery in the near future and improve maternal and infant outcomes.

Objective:To explore the establishment of a Cox proportional hazard prediction model for the re-cent(within a week)delivery of pregnant women with threatened early preterm labor(28-33+6 weeks).Meth-ods:The clinical data of 293 patients with threatened early preterm labor at 28-33+6 weeks admitted to the De-partment of Obstetrics,Affiliated Hospital of North Sichuan Medical College from January 2021 to December 2022 were retrospectively collected.According to whether the patient gave birth recently(within a week)during hospi-talization,they were divided into delivery group(n=88)and non-delivery group(n=205).Demographic data,specialty conditions and clinical biochemical indicators were collected,and the differences of each observation in-dex between the two groups were compared.Cox multivariate analysis was used to screen variables,and then the Cox proportional hazard prediction model was constructed to calculate the hazard ratio(HR).The C-index was used to test the predictive ability of the model,and the nomogram was drawn to visualize the Cox proportional hazard prediction model.The calibration curve was used to test the consistency between the model prediction re-sults and the actual situation.Results:The average age of the delivery group was 30.2±5.0 years old,and the average prolonged pregnancy time was 61.3±47.5 hours.Compared to the group that gave birth and did not give birth,the proportion of patients with body mass index(BMI)at admission,parity＞1,gestational diabetes mellitus or diabetic pregnancy combined(GDM/PGDM),abnormal fetal orientation,regular contractions at admis-sion,vaginal cleanliness≥ Ⅲ,white blood cell count ≥10 ×109/L at admission and cervical length＜20 mm,the difference was statistically significant(P＜0.05).Multivariate Cox regression analysis:BMI＞30 kg/m2(HR 2.178,95％CI 1.208-3.928,P=0.010),parity＞1(HR 3.095,95％CI 1.759-5.447,P＜0.001),regular uterine contraction(HR3.447,95％CI 2.216-5.362,P＜0.001),cervical length＜20 mm(HR3.594,95％CI 2.289-5.646,P＜0.001)and white blood cell count≥10 ×109/L(HR2.124,95％CI 1.352-3.335,P=0.001)on admission were independent risk factors for recent(within a week)delivery of pregnant women with threatened early preterm birth.When the above 5 indicators were included in the prediction model,the C-index was 0.797(95％CI 0.750-0.844),indicating that the model had good prediction ability.The calibration chart shows that the prediction results of the model are in good agreement with the actual results.Conclusions:Preg-nant women with BMI＞30 kg/m2 at admission,parity＞1,regular uterine contraction at admission,cervical length＜20 mm at admission and white blood cell count≥10 ×109/L at admission are prone to premature delivery in the near future.Cox proportional risk prediction model based on the above risk factors has certain accuracy,which can be used to guide clinical workers to take corresponding intervention measures in advance to avoid or reduce the possibility of premature delivery in the near future and improve maternal and infant outcomes.