Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

The key symptom of Shaoyin syndrome,"only wanting to sleep",aligns with the core symptoms of depression,such as"low mood and loss of interest in daily activities".Additionally,the timing of symptom resolution in Shaoyin syndrome,"from 11 PM to 3 AM",corresponds to the pattern of symptom changes in depression.Therefore,depression can be treated from the perspective of Shaoyin syndrome.The fundamental pathogenesis of depression involves Shaoyin heart-kidney yang deficiency.On one hand,heart-kidney yang deficiency leads to spleen yang deficiency,resulting in a lack of nourishment for the spirit.On the other hand,yang deficiency generates dampness,leading to the stagnation of yang qi and a lack of vitality in the spirit.Mahuang Fuzi Gancao Decoction is the primary formula for treating depression based on Shaoyin syndrome.This formula works by supplementing and warming yang,invigorating the heart and kidneys,warming the spleen to dispel cold,and nourishing the spirit to alleviate depression.Additionally,it promotes lung qi,drains water,and expels pathogens to invigorate the spirit.In clinical application,attention should be paid to the preparation of the herbs,dosage,method of decoction,and administration.The formula can also be adjusted with other classic formulas based on the patients'specific symptoms for optimal effectiveness.

Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

The key symptom of Shaoyin syndrome,"only wanting to sleep",aligns with the core symptoms of depression,such as"low mood and loss of interest in daily activities".Additionally,the timing of symptom resolution in Shaoyin syndrome,"from 11 PM to 3 AM",corresponds to the pattern of symptom changes in depression.Therefore,depression can be treated from the perspective of Shaoyin syndrome.The fundamental pathogenesis of depression involves Shaoyin heart-kidney yang deficiency.On one hand,heart-kidney yang deficiency leads to spleen yang deficiency,resulting in a lack of nourishment for the spirit.On the other hand,yang deficiency generates dampness,leading to the stagnation of yang qi and a lack of vitality in the spirit.Mahuang Fuzi Gancao Decoction is the primary formula for treating depression based on Shaoyin syndrome.This formula works by supplementing and warming yang,invigorating the heart and kidneys,warming the spleen to dispel cold,and nourishing the spirit to alleviate depression.Additionally,it promotes lung qi,drains water,and expels pathogens to invigorate the spirit.In clinical application,attention should be paid to the preparation of the herbs,dosage,method of decoction,and administration.The formula can also be adjusted with other classic formulas based on the patients'specific symptoms for optimal effectiveness.

Objective:To investigate the characteristics of cardiopulmonary exercise testing and risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations, to assess their cardiopulmonary health and to provide a basis for improvement.Methods:A case-control study.Sixty-one children with non-acute asthma exacerbations treated at the Outpatient Department of Children′s Hospital of Soochow University from October 2022 to December 2023 and 22 control children during the same period were included.Binary Logistic regression was employed to assess risk factors for decreased aerobic capacity in children with asthma.Results:Among the included 61 children with non-acute asthma exacerbations, there were 33 cases in the chronic persistent phase (chronic persistent phase group) and 28 in the clinical remission phase(clinical remission group).There were 22 children in the control group.During the peak exercise phase of the cardiopulmonary exercise testing, the mean kilogram body weight oxygen uptake (VO 2/kg), the percentage of predicted kilogram body weight oxygen uptake, and metabolic equivalents (Met) in the chronic persistent phase group were lower than those in the control and clinical remission phase groups.The mean VO 2/kg recovery from the cardiopulmonary exercise testing in the first minute in the chronic persistent phase group was lower than that in the control and clinical remission phase groups.The median Met and ventilation per minute recovery in the chronic persistent phase group were lower than those in the control group.The median heart rate recovery in asthma children was lower than that in control children.The percentage of cardiopulmonary exercise testing abnormalities was higher in asthma children with symptoms after excise than that in asthma children without symptoms after excise.The percentage of decreased ventilation efficiency in asthma children with symptoms after excise was higher than that in asthma children without symptoms after excise.Multivariate regression analysis showed that a higher body mass index (BMI) ( OR=1.577, 95% CI: 1.113-2.235, P=0.010) and a higher peak respiratory reserve ( OR=1.103, 95% CI: 1.018-1.195, P=0.017) were risk factors of decreased aerobic capacity.The risk of decreased aerobic capacity in the chronic persistent phase was 7.949 times higher than that in the clinical remission phase ( OR=7.949, 95% CI: 1.290-48.996, P=0.025). Conclusions:The aerobic capacity is decreased and ventilatory recovery is slower in children with chronic persistent asthma than those in healthy children.The heart rate recovery in asthma children is slower than that in healthy children.A high BMI, a high peak respiratory reserve, and chronic persistence of asthma are independent risk factors for decreased aerobic capacity in children with non-acute asthma exacerbations.asthma.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

With the increasing incidence of cardiovascular diseases,Professor WANG Yongyan has adhered to the traditional principles while embracing innovation,proposing to apply the theory of"the heart governing the spirit"to the prevention and treatment of cardiovascular diseases.He emphasized that it is crucial to preserve the spirit before the onset of disease,which includes maintaining a balanced diet,regular lifestyle,avoiding excessive labor,maintaining a serene and unfettered mind,and nurturing the spirit within.For those already suffering from disease,preventing progression and deterioration requires adjusting the spirit,and skilled practitioners should first inspect the patient's spirit by examining the eyes,tongue,facial complexion,and overall physical condition.In treatment,adjusting the spirit involves distinguishing between different imbalances of qi,blood,yin,yang,cold,heat,deficiency,and excess,and employing appropriate method to calm and nourish the spirit accordingly.After the illness,nurturing the spirit is essential,including spiritual nourishment through exercise,dietary therapy,emotional therapy,and external treatments.By applying the theory of"the heart governing the spirit"throughout the prevention,treatment,and rehabilitation of cardiovascular diseases,Professor WANG Yongyan's approach effectively prevents the occurrence of cardiovascular diseases,controls their progression,inhibits deterioration,and improves the prognosis of patients.

ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg^-1）， gentianoside with magnoflorine group （150.454 1 mg·kg^-1+5.061 8 mg·kg^-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg^-1+16.433 1 mg·kg^-1）， sweroside with magnoflorine group （3.455 8 mg·kg^-1+5.061 8 mg·kg^-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg^-1+16.433 1 mg·kg^-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg^-1+5.061 8 mg·kg^-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg^-1+16.433 1 mg·kg^-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E₂ （PGE₂）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE₂， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE₂， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.