AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

Objective:To investigate the clinical characteristics of limb overgrowth following proximal femoral osteotomy (PFO) for unilateral developmental dysplasia of the hip (DDH) in children.Methods:A retrospective analysis was conducted on 36 children with unilateral DDH who underwent PFO at Xi'an Honghui Hospital from June 2017 to June 2021. The cohort included 4 males and 32 females, with a mean age of 4.23±3.15 years (range: 2-12 years), comprising 28 left-sided and 8 right-sided cases. According to the International Hip Dysplasia Institute (IHDI) classification, there were 2 type I, 9 type II, 16 type III, and 9 type IV cases. Radiographic parameters [femoral length, femoral neck anteversion angle, neck-shaft angle, acetabular index (AI), center-edge angle (CEA), center-head distance discrepancy (CHDD)] and PFO parameters (varus angle, shortening length, derotation angle) were measured on X-ray and 3D CT reconstructions. Comparisons were made between the overgrowth ≥1 cm group ( n=14) and <1 cm group ( n=22) to analyze risk factors and patterns. Results:The overgrowth ≥1 cm group had significantly younger patients (2.49±1.03 years vs. 5.13±3.47 years, t=-2.757, P<0.001). Overgrowth magnitude varied significantly across age subgroups: 11.08±6.17 mm in the 2-4 years group, 5.08±0.19 mm in the >4-<6 years group, and 2.44±4.50 mm in the ≥6 years group ( F=5.436, P=0.031). The highest incidence of overgrowth occurred in the 2-4 years subgroup (56%, 20/36). Limb overgrowth initiated at 3 months postoperatively, exhibited a linear correlation with follow-up duration during 6-18 months [ r=0.78, 95% CI(0.62, 0.88), P<0.001)], and plateaued after 18 months [ r=-0.15, 95% CI(-0.75, 0.57), P=0.710]. Postoperative CEA and CHDD showed significant improvements ( P<0.05), while AI remained unchanged ( P>0.05). Conclusions:Children aged 2-4 years exhibit higher incidence and severity of post-PFO limb overgrowth. The rapid progression phase occurs within 6-18 months postoperatively, stabilizing thereafter. CEA and CHDD serve as critical indicators for evaluating intervention efficacy in DDH-related overgrowth.

AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

Objective:To investigate the clinical characteristics of limb overgrowth following proximal femoral osteotomy (PFO) for unilateral developmental dysplasia of the hip (DDH) in children.Methods:A retrospective analysis was conducted on 36 children with unilateral DDH who underwent PFO at Xi'an Honghui Hospital from June 2017 to June 2021. The cohort included 4 males and 32 females, with a mean age of 4.23±3.15 years (range: 2-12 years), comprising 28 left-sided and 8 right-sided cases. According to the International Hip Dysplasia Institute (IHDI) classification, there were 2 type I, 9 type II, 16 type III, and 9 type IV cases. Radiographic parameters [femoral length, femoral neck anteversion angle, neck-shaft angle, acetabular index (AI), center-edge angle (CEA), center-head distance discrepancy (CHDD)] and PFO parameters (varus angle, shortening length, derotation angle) were measured on X-ray and 3D CT reconstructions. Comparisons were made between the overgrowth ≥1 cm group ( n=14) and <1 cm group ( n=22) to analyze risk factors and patterns. Results:The overgrowth ≥1 cm group had significantly younger patients (2.49±1.03 years vs. 5.13±3.47 years, t=-2.757, P<0.001). Overgrowth magnitude varied significantly across age subgroups: 11.08±6.17 mm in the 2-4 years group, 5.08±0.19 mm in the >4-<6 years group, and 2.44±4.50 mm in the ≥6 years group ( F=5.436, P=0.031). The highest incidence of overgrowth occurred in the 2-4 years subgroup (56%, 20/36). Limb overgrowth initiated at 3 months postoperatively, exhibited a linear correlation with follow-up duration during 6-18 months [ r=0.78, 95% CI(0.62, 0.88), P<0.001)], and plateaued after 18 months [ r=-0.15, 95% CI(-0.75, 0.57), P=0.710]. Postoperative CEA and CHDD showed significant improvements ( P<0.05), while AI remained unchanged ( P>0.05). Conclusions:Children aged 2-4 years exhibit higher incidence and severity of post-PFO limb overgrowth. The rapid progression phase occurs within 6-18 months postoperatively, stabilizing thereafter. CEA and CHDD serve as critical indicators for evaluating intervention efficacy in DDH-related overgrowth.

Objective:To construct the risk prediction model of unplanned readmission for elderly patients in emergency department within 30 days based on different machine learning algorithms, so as to help clinical staff identify high-risk patients early and formulate preventive interventions.Methods:A total of 1 207 elderly patients admitted to the emergency department of the First Affiliated Hospital of Naval Medical University from May 2022 to December 2023 were retrospectively selected as the study objects and were divided into the training set ( n = 842) and the test set ( n = 365) in a ratio of approximately 7∶3. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen the factors affecting the unplanned readmission of elderly patients within 30 days. Six prediction models, including extreme Gradient Boost (XGBoost), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost) Logistic regression, K-nearest neighbor (KNN) and Gauss Naive Bayes classification (GNB) were constructed respectively. The models were summarized, evaluated and validated, and the importance of key variables was analyzed using Shapley Additive Interpretation (SHAP). Results:Among 1 207 elderly patients, there were 842 in the training set, 430 males with a median age of 77 years, and 365 in the test set, 176 males with a median age of 78 years. Eight variable features were selected by LASSO regression. The GNB model performed the best among the 6 prediction models constructed based on XGBoost, LightGBM, AdaBoost, Logistic regression, KNN, GNB. The AUC of the test set was 0.818, and the sensitivity was 0.890, while the specificity was 0.660, and the train set and the verification set had strong fitting ability and high stability. The eight characteristics affecting the unplanned readmitted of elderly patients in the emergency department within 30 days were ranked in importance by age, chronic obstructive pulmonary disease, length of stay, Charson comorbidity index≥3, hypoproteinemia, abnormal vital signs≥2, stroke, anemia.Conclusions:The GNB model based on machine learning algorithms for unplanned readmission of elderly emergency patients within 30 days has good predictive performance, which helps medical staff to identify high-risk patients as early as possible before discharge, formulate targeted preventive measures, thereby reducing the short-term unplanned readmission rate of patients and improving their quality of life.

OBJECTIVES: To investigate the risk factors of recurrence of acute ischemic stroke (AIS) within 1 year and establish a nomogram model for predicting the recurrence risk. METHODS: This study was conducted in two cohorts of AIS patients (≤7 days) hospitalized in Dongzhimen Hospital (modeling set) and Fangshan Hospital (validation set) from March, 2021 to March, 2022. Lasso regression analysis was used to identify the important predictive factors for AIS recurrence within 1 year, and multivariate Logistic regression analysis was performed to analyze the independent factors affecting AIS recurrence. The recurrence risk prediction nomogram model was constructed using R studio, and its discriminating power and calibration were assessed using ROC curve analysis and Hosmer-Lemeshow goodness-of-fit test. RESULTS: The modeling and validation sets contained 28 cases (15.22%) and 21 cases (15.00%) of AIS recurrence, respectively. In the modeling set, compared with the non-relapse group, the recurrence group had higher proportions of patients with age >65 years, diabetes, arrhythmia, constipation after stroke, and FBG >7.5 and significantly higher levels of NLR, UREA, Cr, HbA1c, FIB and TT (P<0.05). Multivariate Logistic regression analysis showed that an age >65 years, arrhythmia, constipation after stroke, FBG >7.5, NLR and Cr were all independent risk factors of AIS recurrence (P<0.05). Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis showed that the risk prediction model had good fitting between the modeling set and the verification set. The ROC curve showed that for predicting AIS recurrence within 1 year, the AUC of the predictive model was 0.857 (95%CI: 0.782-0.932) in the modeling set and 0.679 (95%CI: 0.563-0.794) in the validation set. CONCLUSIONS The nomogram model established based on age >65 years, arrhythmia, constipation after stroke, FBG >7.5, NLR and Cr has a good predictive value for AIS recurrence within 1 year.
Humans ; Nomograms ; Risk Factors ; Recurrence ; Ischemic Stroke/etiology* ; Female ; Male ; Logistic Models ; Aged ; ROC Curve ; Middle Aged ; Stroke/etiology*

Objective:To investigate the clinical features,differential diagnosis and treatment of intravascular NK/T cell lymphoma.Methods:The clinical data and diagnosis and treatment process of 2 patients with intravascular NK/T cell lymphoma admitted to Chongqing University Cancer Hospital were retrospectively analyzed, and related literatures were reviewed.Results:Both patients were initially presented with cutaneous symptoms. Patient 1 was diagnosed with intravascular NK/T cell lymphoma, and received 4 courses of programmed-death receptor 1 (PD-1) inhibitor toripalimab + P-Gemox (pegaspargase + gemcitabine + oxaliplatin) regimen, 1 course of PD-1 + ME (toripalimab + mitoxantrone + etoposide) regimen and then underwent autologous hematopoietic stem cell transplantation; patient 2 was diagnosed with intravascular NK/T cell lymphoma involving the nasal cavity, and received 4 courses of P-Gemox regimen, and then received autologous hematopoietic stem cell transplantation in the other hospital. Both patients achieved good therapeutic efficacy.Conclusions:Intravascular NK/T cell lymphoma is very rare, frequently involving the skin and central nervous system. Intravascular growth of tumor cells derived from NK cells is the key point of diagnosis and differential diagnosis. P-Gemox regimen and hematopoietic stem cell transplantation could bring better curative effect.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Objective To investigate the effect of prevascularized tissue-engineered bone graft on regeneration of femoral bone defects in rats.Methods Models of femoral bone defect were created at the bilateral hind limbs of 20 healthy female 10 week-old rats which were divided into 2 even groups randomly (n =10).In group A,conventional tissue-engineered bone grafts were transplanted into the femoral bone defects;in group B,tissue-engineered bone grafts and vascular bundles were implanted into the femoral defects.At 1,4 and 8 weeks after operation,3 rats were sacrificed each time in each group to harvest samples.The remaining one in each group served as a spare animal.Regeneration of bone defects and degradation of scaffolds were assessed by radiologic modality and hematein eosin staining.Results At week 1,the new bone ratio (BV/TV) was 5.47％ ± 1.90％ in group A and 8.49％ ± 1.26％ in group B,showing no significant difference (P ＞ 0.05);at weeks 4 & 8,the BV/TV were 17.54％ ±2.04％ and 39.73％ ± 4.01％ in group A,significantly lower than those in group B (25.32％ ± 2.15％ and 53.22％ ± 2.94％) (P ＜ 0.05).At weeks 1 & 4,the scaffold degradation ratios (RSV/SV) were 97.33％ ± 2.52％ and 80.60％ ±4.00％,showing no significant differences from those in group B (95.67％ ±3.51％ and 75.22％ ±6.20％) (P ＞ 0.05).At week 8,the scaffold degradation ratio in group A (65.46％ ±4.51％) was significantly higher than that in group B (50.19％ ±4.91％) (P ＜ 0.05).At week 8,hematein eosin staining showed better integration of scaffolds with the femur,faster degradation of the interior scaffolds and greater osteogenetic activity in group B.Conclusion Prevascularization of tissue-engineered bone graft may increase new bone volume and scaffold degradation rate,promoting repair of femoral bone defects in rats.

Objective To investigate the effect of sensory and motor nerve homogenates at different concentrations on the proliferation and osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) in rats.Methods The saphenous nerve and the muscle branch of the sciatic nerve in rats were extracted surgically as sensory and motor nerve tissues,respectively.The primary nerve homogenates (10 mg/mL) were prepared as per 10 mg tissue with 1 mL osteoblast inducing conditional media,and 10 times diluted after filtration purification to prepare sensory and motor nerve homogenates at concentration gradients of 1.0,0.1,0.01,0.001 and 0.0001 mg/mL.Cultivation GFP ± rat pups BMSCs in vitro were trained to P3 generation.The experiment was carried out in 3 groups.The sensory and motor nerve homogenates of 500 μL at the above 6 concentration gradients were added during cultivation respectively in the sensory nerve group (n =18) and the motor nerve group(n =18) while 500 μL of osteoblast inducing conditional media was added in the control group(n =3).Cell proliferation quantity detection and alkaline phosphatase (ALP) staining were used to assess the proliferation and differentiation of BMSCs after 14 days.Results According to the results of CCK-8,the cellular absorbance values at concentrations of 1.0 and 0.1 mg/mL homogenate in the sensory nerve group (1.957 ±0.065 and 1.751±0.073) were significantly greater than in the control group (1.145±0.087) while the cellular absorbance value at concentration of 10.0 mg/mL homogenate in the motor nerve group (0.304 ± 0.619) was significandy smaller than in the control group (1.145 ± 0.087) (P ＜ 0.05).According to the ALP staining,the amounts of cellular calcium nodules in the sensory and motor nerve groups (2.667 ± 0.816 and 3.000 ± 0.632,respectively) were significantly smaller than in the control group (11.833 ± 1.471) (P ＜ 0.05).Conclusion Sensory nerve homogenate is different from motor nerve homogenate in that it may promote proliferation of BMSCs and inhibit osteogenesis differentiation of BMSCs in a certain rage of concentrations.