OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Facing of mounting resource constraints and rising demands for personalization in medical education,regional anatomy teaching urgently requires transformation.In this paper,we focus on the regional anatomy of the thoracic wall,in order to explore a novel AI-driven teaching paradigm.Anchored in the core principle of"virtual-real integration with cadaveric dissection as the cornerstone,"the paradigm redefines educational objective and constructs an intelligent,closed-loop teaching model integrating students,computers,and instructors.Leveraging the robust support of digital intelligence(e.g.,DeepSeek),this paradigm incorporates interactive method including group collaboration,branching instruction,and gamified assessments.It achieves a comprehensive intelligent transformation of the entire teaching process-from goal setting and plan customization to activity implementation,task completion,outcome exchange,multidimensional evaluation,and reflective iteration.This new paradigm centers on medical students and leverages digital intelligence to activate deep personalized learning potential.It seamlessly integrates fundamental anatomical knowledge with clinical scenarios(e.g.,key anatomy in breast cancer surgery,flap design in breast reconstruction),and significantly enhances clinical decision-making abilities,scientific research and innovative thinking,as well as medical humanistic literacy,paving a new path for intelligent medical education.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

OBJECTIVE: To explore the protective effect of glycosaminoglycans (GAG) on vascular endothelium in patients with sepsis. METHODS: A prospective study was conducted on adult patients with sepsis admitted to the intensive care unit (ICU) of Hangzhou Normal University Affiliated Hospital from December 2022 to December 2023. Patients were randomly divided into conventional treatment group and GAG intervention group. Both groups were treated according to the 2021 Surviving Sepsis Campaign Guidelines. The GAG intervention group was additionally treated with GAG (2 mL of sulodexide intramuscular injection once daily for 7 days) on the basis of conventional treatment. Venous blood was collected from patients at 0, 6, 24, 48, 72 hours and 7 days after enrollment to detect serum vascular endothelial glycocalyx [heparan sulfate (HS) and syndecan-1 (SDC-1)], inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], and coagulation markers [prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin-III (AT-III), fibrinogen (Fib), D-Dimer], and to perform acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and International Society on Thrombosis and Haemostasis (ISTH) scores. The prognosis of patients (length of hospital stay, ICU and 28-day mortality) was observed. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of HS in predicting the prognosis of sepsis patients, and the correlation between endothelial glycocalyx degradation products and various clinical indicators was analyzed. RESULTS: A total of 50 adult patients with sepsis meeting the inclusion criteria were enrolled, with 25 in the conventional treatment group and 25 in the GAG intervention group. In terms of degradation products of endothelial glycocalyx, compared to baseline, both groups showed an increasing trend in HS and SDC-1 levels post-treatment. However, the GAG intervention group exhibited significantly lower HS levels at 72 hours and 7 days, as well as lower SDC-1 levels at 6, 24, 48, 72 hours and 7 days compared to the conventional group. Among the surviving patients, the HS levels at 72 hours and SDC-1 levels at 6 hours of treatment in the GAG intervention group were significantly reduced compared to the conventional treatment group. In terms of severity score, compared with before treatment, the GAG intervention group showed a significant decrease in APACHE II, SOFA, and ISTH scores after 7 days of treatment. The SOFA scores of the GAG intervention group after 48 hours and 7 days of treatment were significantly lower than those of the conventional treatment group. In terms of inflammatory indicators, compared with before treatment, the GAG intervention group showed a significant decrease in IL-6 levels after 48 hours of treatment. With the prolongation of treatment time, the CRP levels of both groups of patients showed a significant downward trend, and at 7 days of treatment, the CRP level in the GAG intervention group was significantly lower than that in the conventional treatment group. In terms of coagulation function, with prolonged treatment time, PT and APTT of both groups of patients showed an increasing trend, while Fib showed a decreasing trend. The GAG intervention group showed a significant prolongation of PT after 72 hours of treatment compared to the conventional treatment group. In terms of prognosis, there were no statistically significant differences in ICU and 28-day mortality rates between the two groups. The GAG intervention group had significantly shorter hospital stays than the conventional treatment group. ROC curve analysis showed that HS, CRP, APTT, IL-6, APACHE II, SOFA, and ISTH scores were predictive factors for the prognosis of sepsis patients (all P < 0.05). Compared to a single indicator, the combined detection of multiple indicators has a higher value in predicting the prognosis of sepsis patients [area under the curve (AUC) = 0.911, 95% confidence interval (95%CI) was 0.817-1.000], with a sensitivity of 76.9% and a specificity of 91.9%. Correlation analysis showed that HS was significantly negatively correlated with Fib, PT, TNF-α, IL-6, and PCT (r values were -0.338, -0.396, -0.288, -0.319, and -0.340, all P < 0.05), while HS was significantly positively correlated with D-Dimer and CRP (r values were 0.347 and 0.354, both P < 0.05); SDC-1 was significantly negatively correlated with Fib, PT, APTT, TNF-α, IL-6, and ISTH scores (r values were -0.314, -0.294, -0.408, -0.353, -0.289, -0.287, all P < 0.05). CONCLUSIONS Early glycocalyx degradation can occur in sepsis patients. GAG have a protective effect on,the vascular endothelium, reducing the severity of sepsis and providing organ protection. HS, CRP, APTT, IL-6, APACHE II score, SOFA score, and ISTH score are independent predictive factors for the prognosis of sepsis patients. The combination of HS and the above indicators can significantly improve the accuracy of prediction.
Humans ; Sepsis/blood* ; Glycocalyx/drug effects* ; Glycosaminoglycans/pharmacology* ; Prospective Studies ; Endothelium, Vascular/metabolism* ; Syndecan-1/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; Interleukin-6/blood* ; Heparitin Sulfate/blood* ; Middle Aged ; Adult ; Tumor Necrosis Factor-alpha/blood* ; Procalcitonin/blood*

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective:To investigate protective effect and mechanism of Tim-3 on sepsis-induced acute lung injury(ALI)by pro-moting mitophagy of alveolar macrophages and inhibiting activation of NLRP3 inflammasome.Methods:LPS-stimulated mouse alveo-lar macrophage(MH-S)model and sepsis-induced ALI mouse model were constructed.Tim-3 siRNA interference technique was used to knock down Tim-3 expression in MH-S cells,and anti-Tim-3 antibody mice were injected intraperitoneally to block Tim-3 function.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved-caspase-1 and mitophagy-related proteins(LC3B,P62,PINK1 and Parkin)in MH-S cells and lung tissue of mice with sepsis-induced ALI.Laser confocal fluorescence staining was used to measure ROS level and mitochondrial membrane potential of MH-S cells.Pathological examination of lung tissue was performed in mice with sepsis-induced ALI in each group,and degree of lung tissue injury was evaluated by Smith scoring system.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected from mice with ALI induced by sepsis in each group.BCA protein quantification method was used to determine protein concentration in BALF.MPO activity in lung tissue was detected by colorimetry.MDA content in lung tissue was detected by TBA method.LC3B protein expression in lung tissue was detected by immunohistochemistry.Results:In mouse alveolar macrophages,Tim-3 knockdown could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins,increase ROS release,inhibit PINK1/Parkin pathway activation and LC3B protein expression,and reduce mitochondrial membrane potential.In mice with sepsis-induced ALI,Tim-3 functional blockade could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins in lung tissue,aggravate lung pathological injury and pulmonary edema,increase MPO activity and MDA content in lung tissue,and reduce positive rate of LC3B protein.Conclusion:Tim-3 plays a protective role in sepsis-induced ALI by promoting mitophagy in alveolar macrophages and inhibiting NLRP3 inflammasome activation via PINK1/Parkin.

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.