In the context of the digital-intelligent era of traditional Chinese medicine （TCM）， the lack of clinical thinking is a pressing issue that limits the overall effectiveness of TCM and talent cultivation. The "disease-pulse-syndrome-treatment differentiation" thinking model， originally developed by ZHANG Zhongjing in the Treatise on Cold Damage and Miscellaneous Diseases （Shang Han Za Bing Lun）， has served as a guideline and paradigm followed by generations of medical practitioners. This study aims to construct a digitalized "disease-pulse-syndrome-treatment differentiation" thinking system， develop a digital assessment system， and implement it for practical application. The goal is to recommend a digitalized assessment model for TCM and provide a reference for the integrated innovation of talent cultivation in medicine， education， and research. First， based on the complex diagnostic and treatment framework of the Treatise on Cold Damage Diseases （Shang Han Lun）， the research team previously established a "process" + "result" thinking model that included four processes and ten steps. This study integrates knowledge unit theory and digital technology to create a digital system for "disease-pulse-syndrome-treatment differentiation" with a dual-control model of "process control" and "result control". The system consists of 46 items across three categories： knowledge body （W=20%）， knowledge element （W=30%）， and knowledge element associations （W=50%）. Second， a mixed-methods research design was employed， combining qualitative and quantitative approaches. The Delphi method was used to establish hierarchical levels and screen items， while the analytic hierarchy process （AHP） was used to assign weights. Expert surveys were conducted to reach a consensus and further validate the rationale and necessity of the system. Finally， based on the system architecture and integrating key computer technologies， a digital assessment system for "disease-pulse-syndrome-treatment differentiation" was developed. The Treatise on Cold Damage Diseases （Shang Han Lun） was used as a case study to validate the system's feasibility. Statistical results showed that the difficulty level of the assessment question bank was moderate （DL ranging from 0.65 to 0.89）， with good discrimination （D>0.4）， and reasonable reliability and validity （Cronbach's α=0.84， KMO=0.72， Bartlett's test P<0.01）. The system can perform process-oriented evaluations of candidates' thinking in "disease-pulse-syndrome-treatment differentiation" and effectively achieve the goal of clinical thinking assessment through a combination of "process control" and "result control". The examination system offers three major advantages. It standardizes， objectifies， and streamlines the assessment of thought processes， facilitates the organic transformation of TCM education from outcome-based education to thinking-based education， and from exam-oriented education to competency-oriented education， and promotes the practical transformation of TCM assessments from qualitative to quantitative evaluation， as well as from theory to practice. In summary， this system not only represents a technological upgrade to traditional examinations but also empowers the cultivation and assessment of clinical talent in the digital-intelligent era， demonstrating broad application prospects.

Objective:To explore the prognosis and influencing factors of early-onset neonatal sepsis (EONS), and provide the guidance for early clinical prevention and treatment.Methods:The clinical data of 147 children with EONS in Shijiazhuang Maternal and Child Health Hospital from January 2019 to December 2023 were retrospectively analyzed. The baseline data and prognosis data (good prognosis and poor prognosis) were recorded. Multivariate Logistic regression analysis was used to analyze the risk factors of poor prognosis in children with EONS. R3.5.3 software package was used to build a nomogram model for predicting poor prognosis in children with EONS, and the rms package was used to calculate the consistency index ( C- index), and Bootstrap self-sampling was used for internal verification. Results:Among the 147 children with EONS, 41 children (27.89%) had poor prognosis, and 106 children (72.11%) had good prognosis. The incidence of thrombocytopenia, incidence of bacterial meningitis, procalcitonin and lactate in children with poor prognosis were significantly higher than those in children with good prognosis: 68.29% (28/41) vs. 17.92% (19/106), 43.9% (18/41) vs. 1.89% (2/106), (70.36 ± 13.45) ng/L vs. (42.76 ± 10.37) ng/L and (6.18 ± 2.05) mmol/L vs. (4.22 ± 1.05) mmol/L, and there were statistical differences ( P<0.01); there were no statistical difference in gender composition, gestational age, birth weight, 1 min Apgar score, delivery mode, white blood cell, C-reactive protein, creatinine and the incidences of placental abruption, amniotic fluid contamination, maternal infection, necrotizing enterocolitis between the two groups ( P>0.05). Multivariate Logistic analysis result showed that thrombocytopenia, bacterial meningitis, high procalcitonin and high lactate were the independent risk factors for poor prognosis in children with EONS ( OR = 9.595, 22.657, 1.213 and 2.614; 95% CI 1.094 to 20.055, 1.833 to 41.328, 0.745 to 0.937 and 0.990 to 1.209; P<0.05 or <0.01). A nomogram model was constructed to predict poor prognosis in children with EONS, using thrombocytopenia, bacterial meningitis, procalcitonin and lactate as predictive factors. The nomogram model predicted that the correction curve for poor prognosis in children with EONS tended towards the ideal curve ( C- index = 0.987, 95% CI 0.975 to 0.998). Conclusions:The children with EONS have a higher risk of adverse prognosis, which may be related to their comorbidities with thrombocytopenia, bacterial meningitis, high procalcitonin and high lactate at diagnosis. The nomogram model established based on the indexes has a good predictive effect on the disease prognosis.

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

Cryopreservation is the primary technique for in vitro preservation of allogeneic tissue. However, its success is often hindered by factors such as low temperature, ischemia, and hypoxia. This study investigated the potential of Sini Decoction, known for its antioxidant and anti-apoptotic properties, to reduce cryopreservation-induced injury in rats' sciatic nerves. Sini Decoction was prepared according to the Chinese Pharmacopoeia, and its cytotoxicity on Rsc96 cells was assessed by using the CCK-8 method. Sini Decoction at concentrations of 4, 8, and 16 mg·mL~(-1), termed as low-(SL), medium-(SM), and high-(SH) doses group, was used for cryopreservation of rats' sciatic nerves. A normal control(NC) group and a fresh nerve control(fresh) group were set. Flow cytometry and TUNEL staining were used to detect the apoptosis of neural tissue cells after cryopreservation. Western blot was used to detect the expression of apoptosis-related proteins(Bcl-2, Bax, caspase-3, and caspase-8) and nerve regeneration proteins(NGF and BDNF) in vitro after cryopreservation. Oxidative damage of neural tissue after cryopreservation was evaluated by measuring levels of GSH, SOD, MDA, ROS, and ATP. Cryopreserved nerves were then used for allogeneic transplantation. One week after transplantation, CD4~+ and CD8~+ fluorescent double staining assessed inflammatory cell invasion in the transplanted nerve segment, and ELISA evaluated the expression of serum inflammatory factors(IL-1, IFN-γ, and TNF-α) in recipients. Twenty weeks after transplantation, electrophysiology and NF200 neurofilament staining were used to evaluate nerve regeneration. RESULTS:: showed that Sini Decoction at concentrations of below 32 mg·mL~(-1) exhibited no cytotoxicity to Rsc96 cells. During in vitro nerve cryopreservation, Sini Decoction significantly reduced cell apoptosis, ROS, and MDA production compared to the NC group. In the SH group, the protein expression of NGF and BDNF in vitro, as well as ATP, SOD, and GSH production, were significantly increased. In the rejection reaction one week after transplantation, compared to the fresh nerve transplantation group, the SL and SM groups showed reduced CD4~+ and CD8~+ T cell invasion in the transplanted nerve segment and down-regulated IL-1, IFN-γ, and TNF-α expression in recipient serum. Twenty weeks after transplantation, the electrophysiological test results of CMAP, NCV, and NF200 neurofilament protein fluorescent staining in the SM and SH groups were superior to those in the NC and fresh groups. These findings indicate that Sini Decoction offers protective benefits in the cryopreservation of rats' sciatic nerves and holds significant potential for the in vitro preservation of tissue and organs.
Animals ; Apoptosis/drug effects* ; Rats ; Oxidative Stress/drug effects* ; Sciatic Nerve/cytology* ; Cryopreservation ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Protective Agents/pharmacology*

Objective To explore the relationship between C-reactive protein/albumin ratio(CAR)and the disease severity in patients with severe pneumonia,and its predictive value for 28-day mortality risk.Methods A retrospective analysis was conducted on 152 patients with severe pneumonia admitted to Fuyang People's Hospital from January 2020 to January 2022.They were divided into non-critical illness group(n=51),critical illness group(n=63),and extremely critical illness group(n=38)based on the disease severity.The clinical data such as age and gender of patients was collected,and Pearson correlation analysis was used to explore the correlation between CAR and the severity of illness[determined by Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score].Multivariate logistic regression was employed to identify independent influencing factors of the severity of illness.According to the survival status of patients after 28 days of treatment,they were divided into survival group(n=107)and death group(n=45).CAR was categorized into quintiles(Q1-Q5),and multivariate logistic regression analysis was conducted to explore the correlation between CAR and 28-day mortality risk in severe pneumonia patients.A restricted cubic spline(RCS)model was used to analyze the dose-response relationship between CAR and mortality risk.The predictive value of CAR and related indicators for patient mortality risk was evaluated using the receiver operating characteristic curve(ROC).Results CAR was significantly positively correlated with the severity of the disease(APACHE Ⅱ score)(r=0.716,P<0.05).Neutrophil/lymphocyte ratio(NLR),blood lactate(Lac),and high CAR were independent risk factors for the disease severity in patients with severe pneumonia(P<0.05).After adjusting for confounding factors,the mortality risk increased with the increase of CAR(P<0.05).Subgroup analysis of the screened confounding factors revealed that the correlation between CAR and 28-day mortality risk in severe pneumonia patients remained stable across different APACHE Ⅱ scores,GCS scores,SOFA scores,white blood cell counts(WBC),neutrophils(NEU),red cell volume distribution width(RDW),procalcitonin(PCT),and Lac,with interactions observed between NLR and Lac subgroups(P<0.05).The RCS model indicated that there was no non-linear dose-response relationship between CAR and 28-day mortality risk in patients with severe pneumonia of different genders.ROC curve analysis showed that CAR,Lac,and NLR had good predictive value for 28-day mortality in severe pneumonia patients,with the combined predictive efficacy being significantly higher than that of individual indicators.Conclusion There is a close relationship between CAR and the progression and prognosis of severe pneumonia,making it a new approach to assessing the severity of illness and predicting mortality risk in patients.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To explore the influencing factors of brain injury in children with neonatal asphyxia after resuscitation.Methods:The clinical data of 180 children with neonatal asphyxia from January 2017 to January 2024 in Shijiazhuang Maternal and Child Health Hospital were retrospectively analyzed, and all children were received resuscitation treatment. The children were divided into modeling group (126 cases) and validation group (54 cases) in a 7∶3 ratio. Among the children in modeling group, 51 children combined brain injury (brain injury subgroup), and 75 children did not combine brain injury (non-brain injury subgroup). The general data were recorded, and the continuous variables were determined by the receiver operating characteristic (ROC) curve to determine the optimal cut-off value. Multivariate Logistic regression analysis was used to analyze the independent risk factors of brain injury in children with neonatal asphyxia after resuscitation. The R language software "rms" package was used to construct a nomogram model for predicting brain injury in children with neonatal asphyxia after resuscitation. The nomogram model was internally verified by the calibration curve, and the prediction efficiency of the nomogram model was evaluated by the decision curve and ROC curve.Results:There was no statistical difference in general data between modeling group and validation group ( P>0.05). The gestation age<37 weeks proportion, severe asphyxia proportion, Ⅱ to Ⅲ grade amniotic fluid contamination proportion, intrauterine distress proportion and blood lactate in brain injury subgroup were significantly higher than those in non-brain injury subgroup: 60.78% (31/51) vs. 38.67% (29/75), 37.25% (19/51) vs. 17.33% (13/75), 27.45% (14/51) vs. 10.67% (8/75), 47.06% (24/51) vs. 26.67% (20/75) and (2.64 ± 0.61) mmol/L vs. (2.21 ± 0.56) mmol/L, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in gender composition, birth weight, maternal age, maternal history of adverse pregnancy and childbirth, mode of delivery, parity, abnormal amniotic fluid volume, abnormal fetal position, abnormal umbilical cord, abnormal placenta, systolic blood pressure, diastolic blood pressure, body temperature and blood glucose between the two groups ( P>0.05). ROC curve analysis result showed that the optimal cutoff value of blood lactate was 2.59 mmol/L. Multivariate Logistic regression analysis result showed that the young gestation age, severe asphyxia, Ⅱ to Ⅲ grade amniotic fluid contamination, intrauterine distress and high blood lactate were independent risk factors of brain injury in children with neonatal asphyxia after resuscitation ( OR = 2.854, 3.428, 3.405, 3.427 and 7.844; 95% CI 1.166 to 6.983, 1.263 to 9.305, 1.076 to 10.768, 1.358 to 8.645 and 3.080 to 19.978; P<0.05 or <0.01). The gestation age, degree of asphyxia, amniotic fluid contamination, intrauterine distress and blood lactate were used as predictors to construct a nomogram model for predicting brain injury in children with neonatal asphyxia after resuscitation. The calibration curve analysis result showed that the calibration curve of the nomogram model for predicting brain injury in children with neonatal asphyxia after resuscitation tended towards the ideal curve ( C- index = 0.824, 95% CI 0.745 to 0.903). The decision curve analysis result showed that, when the risk threshold was greater than 0.18, the clinical net benefits provided by the nomogram model were higher than those of a single independent risk factor, and it could provide significant additional clinical net benefits in predicting the high risk of brain injury in children with neonatal asphyxia after resuscitation. ROC curve of internal validation analysis result that the curve (AUC) of the nomogram model for predicting brain injury in children with neonatal asphyxia after resuscitation was 0.824 (95% CI 0.744 to 0.903). ROC curve of external validation result showed that the AUC of the nomogram model for predicting brain injury in children with neonatal asphyxia after resuscitation was 0.838 (95% CI 0.714 to 0.962). Conclusions:The gestation age, degree of asphyxia, amniotic fluid contamination, intrauterine distress and blood lactate are independent risk factors for brain injury in children with neonatal asphyxia after resuscitation. The nomogram model constructed based on these factors has a high clinical benefit in predicting brain injury in children with neonatal asphyxia after resuscitation.