Objective:To investigate relationship between serum immunoglobulin(Ig),forkhead box protein P3(Foxp3)and therapeutic effect of nivolumab in patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 180 advanced NSCLC patients admitted to Hengshui People's Hospital between January 2020 and January 2024 were selected as NSCLC group,and 180 healthy individuals who underwent physical examinations during same period were selected as healthy group.Serum IgA,IgM,IgG and Foxp3 levels were measured,and differences in serum IgA,IgM,IgG and Foxp3 levels between two groups were compared,as well as their differences of levels in different clinical characteristics of advanced NSCLC patients.Advanced NSCLC patients were treated with nivolumab on basis of paclitaxel and carboplatin chemotherapy,and divided into treatment effective group(n=82)and treatment ineffective group(n=98)based on efficacy.Differences of serum IgG and Foxp3 levels between two groups were compared,and efficacy of serum IgG and Foxp3 in predicting therapeutic effect of nivolumab in advanced NSCLC patients was analyzed.Results:Serum IgG and Foxp3 levels in NSCLC group were higher than healthy group(P<0.05),and there was no statistically significant difference in serum IgA and IgM levels between two groups(P>0.05).Serum IgG and Foxp3 levels in TNM stage Ⅳ and poorly differentiated NSCLC patients were higher than stage Ⅲ NSCLC patients(P<0.05).TNM stage Ⅳ,proportion of low differentiation,and serum IgG and Foxp3 levels in ineffective group were higher than effective group(P<0.05).Logistic regression analysis showed that differentiation level,high IgG and high Foxp3 levels were risk factors for ineffective treatment with nivolumab in advanced NSCLC patients(P<0.05).Predictive efficacy of combination of serum IgG and Foxp3 in treatment of advanced NSCLC patients with nivolumab was superior to any single therapy,with an AUC of 0.978,sensitivity of 96.75%,and specificity of 92.13%.Conclusion:Elevated serum IgG and Foxp3 levels in patients with advanced NSCLC are risk factors for nivolumab treatment failure,and can be used as a reference index to predict therapeutic effect of nivolumab.

BACKGROUND:Ankle fracture complicated with deltoid ligament injury is clinically common,and one stage repair of deltoid ligament with internal fracture fixation has gradually become a main therapeutic method,which can significantly reduce the long-term complications of ankle joint.In recent years,new progress has been made in anatomical structure characteristics and dynamic biomechanical research of deltoid ligament,thus greatly improving repairing techniques for injury in the deep layer of deltoid ligament,but there are still some controversies.OBJECTIVE:To explore the clinical efficacy of suture anchor and medial malleolus repair in the treatment of ankle joint fractures with the deep layer of deltoid ligament.METHODS:A total of 56 patients with ankle joint fractures and complete fracture of the deep and superficial layer of deltoid ligament treated in Affiliated Haikou Hospital,Xiangya School of Medicine,Central South University from January 2017 to January 2022 were selected,and they were divided into two groups according to different treatment methods in repairing the deep layer of deltoid ligament with suture anchor:suture anchor repair group(n=32)and medial malleolus repair group(n=24).The medial clear space of ankle joint and American Orthopedic Foot and Ankle Society Score of patients in the two groups were evaluated before and after operative treatment.RESULTS AND CONCLUSION:(1)All the 56 patients finished the surgery smoothly and were followed up for more than 12 months after operation.Their ankle fracture healed,and the time for fracture healing was 8-12 weeks,with a mean of 10.5 weeks.(2)The medial clear space of ankle joint in the two groups 12 months after operation was remarkably narrower than that before operation,and the difference was statistically significant(P＜0.001).The medial clear space of ankle joint in the two groups maintained a normal range 12 months after operation,and there was no statistically significant difference between the two groups(P＞0.05).(3)The AOFAS scale of patients in the two groups 6 and 12 months after operation was obviously bigger than that before operation(P＜0.001),but there was no statistically significant difference in the American Orthopedic Foot and Ankle Society Score of patients between the two groups at corresponding time points(P＞0.05).(4)It is concluded that both suture anchor and medial malleolus repair in the treatment of injury in the deep layer of deltoid ligament can recover the medial clear space of ankle joint,effectively keep the stability of ankle,and thus achieve good clinical efficacy.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

BACKGROUND:Ankle fracture complicated with deltoid ligament injury is clinically common,and one stage repair of deltoid ligament with internal fracture fixation has gradually become a main therapeutic method,which can significantly reduce the long-term complications of ankle joint.In recent years,new progress has been made in anatomical structure characteristics and dynamic biomechanical research of deltoid ligament,thus greatly improving repairing techniques for injury in the deep layer of deltoid ligament,but there are still some controversies.OBJECTIVE:To explore the clinical efficacy of suture anchor and medial malleolus repair in the treatment of ankle joint fractures with the deep layer of deltoid ligament.METHODS:A total of 56 patients with ankle joint fractures and complete fracture of the deep and superficial layer of deltoid ligament treated in Affiliated Haikou Hospital,Xiangya School of Medicine,Central South University from January 2017 to January 2022 were selected,and they were divided into two groups according to different treatment methods in repairing the deep layer of deltoid ligament with suture anchor:suture anchor repair group(n=32)and medial malleolus repair group(n=24).The medial clear space of ankle joint and American Orthopedic Foot and Ankle Society Score of patients in the two groups were evaluated before and after operative treatment.RESULTS AND CONCLUSION:(1)All the 56 patients finished the surgery smoothly and were followed up for more than 12 months after operation.Their ankle fracture healed,and the time for fracture healing was 8-12 weeks,with a mean of 10.5 weeks.(2)The medial clear space of ankle joint in the two groups 12 months after operation was remarkably narrower than that before operation,and the difference was statistically significant(P＜0.001).The medial clear space of ankle joint in the two groups maintained a normal range 12 months after operation,and there was no statistically significant difference between the two groups(P＞0.05).(3)The AOFAS scale of patients in the two groups 6 and 12 months after operation was obviously bigger than that before operation(P＜0.001),but there was no statistically significant difference in the American Orthopedic Foot and Ankle Society Score of patients between the two groups at corresponding time points(P＞0.05).(4)It is concluded that both suture anchor and medial malleolus repair in the treatment of injury in the deep layer of deltoid ligament can recover the medial clear space of ankle joint,effectively keep the stability of ankle,and thus achieve good clinical efficacy.

Objective:To investigate relationship between serum immunoglobulin(Ig),forkhead box protein P3(Foxp3)and therapeutic effect of nivolumab in patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 180 advanced NSCLC patients admitted to Hengshui People's Hospital between January 2020 and January 2024 were selected as NSCLC group,and 180 healthy individuals who underwent physical examinations during same period were selected as healthy group.Serum IgA,IgM,IgG and Foxp3 levels were measured,and differences in serum IgA,IgM,IgG and Foxp3 levels between two groups were compared,as well as their differences of levels in different clinical characteristics of advanced NSCLC patients.Advanced NSCLC patients were treated with nivolumab on basis of paclitaxel and carboplatin chemotherapy,and divided into treatment effective group(n=82)and treatment ineffective group(n=98)based on efficacy.Differences of serum IgG and Foxp3 levels between two groups were compared,and efficacy of serum IgG and Foxp3 in predicting therapeutic effect of nivolumab in advanced NSCLC patients was analyzed.Results:Serum IgG and Foxp3 levels in NSCLC group were higher than healthy group(P<0.05),and there was no statistically significant difference in serum IgA and IgM levels between two groups(P>0.05).Serum IgG and Foxp3 levels in TNM stage Ⅳ and poorly differentiated NSCLC patients were higher than stage Ⅲ NSCLC patients(P<0.05).TNM stage Ⅳ,proportion of low differentiation,and serum IgG and Foxp3 levels in ineffective group were higher than effective group(P<0.05).Logistic regression analysis showed that differentiation level,high IgG and high Foxp3 levels were risk factors for ineffective treatment with nivolumab in advanced NSCLC patients(P<0.05).Predictive efficacy of combination of serum IgG and Foxp3 in treatment of advanced NSCLC patients with nivolumab was superior to any single therapy,with an AUC of 0.978,sensitivity of 96.75%,and specificity of 92.13%.Conclusion:Elevated serum IgG and Foxp3 levels in patients with advanced NSCLC are risk factors for nivolumab treatment failure,and can be used as a reference index to predict therapeutic effect of nivolumab.

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.

Objective:To construct a nomogram for predicting unfavorable prognosis at 6 months after moderate and severe traumatic brain injury (msTBI) and validate its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 387 patients with msTBI who were admitted to 904th Hospital of the Joint Logistic Support Force of PLA from January 2020 to December 2022, including 265 males and 122 females, aged 6-97 years [58(47, 68)years]. According to the Glasgow outcome scale (GOS) score at 6 months after injury, the patients were divided into favorable prognosis group (GOS 4-5 points, n=201) and unfavorable prognosis group (GOS 1-3 points, n=186). The clinical characteristics, imaging manifestations, and laboratory test results of the two groups on admission were recorded. Univariate analysis was applied to evaluate the correlation between the aforementioned indicators and the unfavorable prognosis of the msTBI patients at 6 months after injury. Receiver operating characteristic (ROC) curves of single variable and the correlation heatmap among continuous variables were plotted. Lasso regression was used to select variables and multivariate Logistic regression analysis was used to determine independent predictive factors so as to construct Logistic regression equation and plot the nomogram. The internal verification was carried out by means of random and non-random split of data. In random split, the data were divided randomly with a ratio of 6∶4 into training group ( n=232) and verification group ( n=155). In non-random split, the patients admitted from January 2020 to December 2021 were assigned to the training group ( n=260), while those admitted from January 2022 to December 2022 to the verification group ( n=127). Area under the curve (AUC) was used to evaluate the predictive ability of the model in the training group and verification group, calibration curve and Hosmer-Lemeshow (H-L) test to evaluate its goodness of fit, and decision curve analysis (DCA) to evaluate its clinical applicability. The influence of inclusion of neutrophil-to-lymphocyte ratio (NLR) model on the warning effectiveness of poor prognosis was analyzed in comparison with the model without inclusion of NLR. Results:Univariate analysis showed that there was a certain correlation between age, length of hospital stay, Glasgow coma scale (GCS), American Society of Anesthesiologists Physical Status (ASA-PS) classification, Injury severity score (ISS), prehospital tracheal intubation, hypotension, hypoxia, pupillary responsiveness, midline shift, basilar cisterna status, traumatic subarachnoid hemorrhage (tSAH), D-Dimer, prothrombin time activity (PTA), glucose, hemoglobin, K +, Cl -, Ca 2+, HCO -, creatinine, albumin, lactic acid, platelet, lymphocyte, systemic immune-inflammation index (SII), NLR, lymphocyte-to-monocyte ratio (LMR) and unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The ROC curve of single variable showed that GCS (AUC=0.82), ISS (AUC=0.81), pupillary responsiveness (AUC=0.76), basal cistern status (AUC=0.73) and NLR (AUC=0.73) had good predictive validity. The results of the correlation heatmap showed that there was a significant correlation and collinearity among the continuous variables, while no collinearity was found between ISS and NLR. Fourteen potential predictors selected by Lasso regression were included in multivariate Logistic regression analysis and its results showed that age ( OR=0.86, 95% CI 1.38, 5.19), GCS 6-8 points ( OR=3.13, 95% CI 1.06, 9.27), GCS 3-5 points ( OR=12.36, 95% CI 2.81, 54.27), ISS ( OR=3.68, 95% CI 1.38, 9.80), pupillary responsiveness ( OR=2.45, 95% CI 0.85, 7.07), and NLR ( OR=2.62, 95% CI 1.52, 4.51) were identified as the independent risk factors for unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The multivariate Logistic regression equation was Logit [P/(1-P)]=0.066×"age"+ 1.474×"GCS 6-8"+2.357×"GCS 3-5"+0.066×"ISS"+0.965×"absence of pupillary light reflex"+0.194×"NLR"-10.704. In the internal verification of random split of data, the AUC value of the model was 0.93 (95% CI 0.89, 0.96) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. In the internal verification of non-random split, the AUC value was 0.94 (95% CI 0.91, 0.97) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. The calibration curve and H-L test showed that the model had good calibration ability ( P>0.5). The results of DCA showed that the application of the nomogram would increase the net benefit of the patients (risk threshold probability of 0.0-0.8). Compared with the conventional model (AUC=0.90), inclusion of NLR model (AUC=0.93) enhanced the warning effectiveness. Conclusions:Age, GCS, ISS, pupillary responsiveness and NLR are independent risk factors affecting unfavorable prognosis in msTBI patients at 6 months after injury, based on which the nomogram constructed can better predict the clinical outcome of msTBI patients.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*