ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

ObjectiveTo explore the effects and mechanisms of Naotai Formula （脑泰方） against white matter lesions associated with cerebrovascular disease via Wnt/β-catenin pathway. MethodsTen WKY rats were used as sham surgery group， and 30 spontaneously hypertensive rats （SHRs） were randomly divided into model group， low-and high-dose Naotai Formula group， with 10 rats in each group. In addition to the sham surgery group， rats in each group were modelled by dorsum subcutaneous injection of D-galactose for 56 days， by performing bilateral common carotid artery stenosis on the 29th day of modelling with low perfusion for 28 days to construct the rat models of cerebral small-vessel disease with composite risk factors. The rats in the low- and high-dose Naotai Formula groups were given 9 and 27 g/（kg·d） of Naotai Formula by gavage on the day after surgery， and 10 ml/（kg·d） of pure water by gavage in the sham surgery group and the model group， with all rats in each group gavaged for 4 weeks. Blood pressure of rats was monitored weekly before and after medication administration； water maze experiments were performed for 6 consecutive days from the 50th day of modelling； and changes in cerebral blood flow were detected by laser scattering preoperatively， postoperatively， and after medication administration. The samples were taken on the next day after the last gavage， and the extent of myelin damage in the rat corpus callosum was observed by Lucas fast blue （LFB） and transmission electron microscopy， and the levels of interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， interleukin 10 （IL-10）， and tumour necrosis factor β （TNF-β） were detected by ELISA， and the levels of expression of myelin basic protein （MBP） and ionized calcium binding adaptor molecule 1 （IBA1）， neuroglial antigen 2 （NG2）， cell proliferation marker Ki67 antigen （MBP）， and cell proliferation marker Ki67 antigen （Ki67A）/NG2， 2'，3'- cyclic-nucleotide 3'-phosphodiesterase （CNPase） expression were measured by immunofluorescence. MBP in the corpus callosum， wingless MMTV integration site family member 3a （Wnt3a）， phosphorylated glycogen synthase kinase 3β （p-GSK-3β）， glycogen synthase kinase 3β （GSK-3β）， phosphorylated β-catenin （p-β-catenin）， β-catenin expression were detected by western blotting， and GSK-3β， β-catenin mRNA expression in the corpus callosum were detected by RT-qPCR. ResultsCompared with the sham surgery group， rats in the model group had elevated systolic blood pressure at all time points， decreased the number of traversing platforms and the percentage of time spent in the target quadrant in the water maze experiments， significantly prolonged the evasion latency on days 4 and 5， and decreased cerebral blood flow in the postoperative period and after medication administration （P＜0.05 or P＜0.01）； significant myelin sheath damage in the corpus callosum was seen by LFB staining and transmission electron microscopy； the callus had significantly higher levels of TNF-α and IL-1β content increased， TNF-β content decreased， MBP fluorescence intensity and protein expression decreased， the number of IBA1-positive cells increased， Wnt3a and p-GSK-3β/GSK-3β values increased， p-β-catenin/β-catenin values decreased， GSK-3β mRNA expression decreased， and β-catenin mRNA expression increased （P＜0.05 or P＜0.01）. Compared with the model group， the myelin sheath damage of corpus callosum in rats in the high-dose Naotai Formula groups was significantly improved， and all of the above indexes were significantly improved （P＜0.05 or P＜0.01）. Compared with the low-dose Naotai Formula group， myelin damage in the corpus callosum of the high-dose Naotai Formula group was improved， systolic blood pressure reduced， cerebral blood flow and MBP fluorescence intensity and protein expression in the corpus callosum， the number of positive cells for NG2 and CNPase， the values of p-β-catenin/β-catenin and GSK-3β mRNA expression increased， and the expression of Wnt3a， p-GSK-3β/ GSK-3β values and β-catenin mRNA expression decreased （P＜0.05 or P＜0.01）. ConclusionsHigh-dose Naotai Formula can significantly improve white matter lesions in cerebral small vessel disease， and the mechanism may be related to the inhibition of the Wnt/β-catenin signalling pathway， reducing the inflammatory microenvironment in the brain， and promoting the differentiation of oligodendrocyte precursor cells into oligodendrocytes.

Objective To analyze the blood concentration monitoring results of 7 new antiepileptic drugs levetiracetam(LEV),oxcarbazepine(OXC),lamotrigine(LTG),topiramate(TPM),lacosamide(LCM),zonisamide(ZNS)and perampanel(PER)and provide a basis for clinical rational drug use.Methods Aretrospective analysis was conducted on the blood concentration monitoring results of 7 new antiepileptic drugs in a grade-A tertiary hospital in Beijing from November 2021 to March 2023,with a total of 6 537 valid concentration data collected.The patients were grouped according to age,gender and concomitant medication,and the blood drug concentration levels and compliance rates among the groups were analyzed and compared.Results The male to female patient ratio was 1.35∶1.There were statistically significant differences in the blood concentration distribution of OXC,LEV,LCM and TPM between genders(P<0.05).The blood concentration of LEV showed statistically significant differences between the pediatric group and the elderly group,as well as between the young adult group and the elderly group(P<0.05).The blood concentrations of OXC,ZNS and TPM showed statistically significant differences between the pediatric group and the young and middle-aged group,between the young and middle-aged group and the elderly group,and between the pediatric group and the young and middle-aged group,respectively(P<0.05).The highest and lowest overall compliance rates of blood concentration were observed for OXC and LCM,respectively.The compliance rates of OXC and TPM in the pediatric group were significantly higher than those in the young-middle-aged group,with statistically significant differences(P<0.05),while the compliance rate of LEV in the elderly group was significantly higher than that in the pediatric group and the young-middle-aged group,with a statistically significant difference(P<0.05).There were a total of 2 133 cases with combined drug use.LEV,OXC and LTG are frequently used and have good efficacy and weak interactions when added to treatment.Conclusion New antiepileptic drugs show a promising prospect in treatment,and therapeutic drug monitoring can further improve the effectiveness of individualized clinical treatment.

Objective:To investigate the intention to stay on among primary health care workers (PHWs) during the COVID-19 epidemics and its influencing factors.Methods:An online questionnaire survey was conducted among PHWs from 62 primary health institutions in 31 provinces, autonomous regions and municipalities across China selected by multi-stage whole cluster random sampling method between May and October 2022. According to the job position, the PHWs were divided into 5 categories: general practitioners (GPs), nurses, public health doctors, managers and support staff. Intention to stay was measured using the Chinese version of the Intention to Stay Questionnaire. Multiple linear regression model was used to analyze the influencing factors of the intention to stay in PHWs of different occupational categories, including personal factors, work factors, factors related to the COVID-19 and psychological reactions.Results:A total of 3 769 PHWs from 44 community health service centers, 18 township hospitals of 27 provinces/autonomous regions and 4 municipalities participated in this survey. The mean age of participants was (37.4±9.2) years, including 2 971(78.8%) women. The mean score of intention to stay of participants was 21.7±4.1. Compared with GPs, managers had lower intention to stay ( P=0.004). Age, female, in marriage, monthly income, years of primary care service, self-evaluation of unit support function, MSQ-SF score, and PA score were positively correlated with the score of intention to stay (all P<0.05), while PHQ-9 score, EE score, and DP score were negatively correlated with the score of intention to stay (all P<0.05). The MSQ-SF scores of all occupational categories were positively correlated with the scores of intention to stay (all P<0.01). In addition, among GPs, monthly income, years of service in primary care, self-evaluation of unit support function, and PA scores were positively correlated with the score of intention to stay (all P<0.05), while PHQ-9 scores and EE scores were negatively correlated with the score of intention to stay (all P<0.05). Among nurses, age, female gender, monthly income, self-evaluation of unit support function, and PA score were positively correlated with the score of intention to stay (all P<0.05), while EE scores and retention will score were negatively associated with ( P<0.001). Among public health doctors, in marriage was positively correlated with the score of intention to stay ( P=0.018). Among managers, DP score was negatively correlated with the score of intention to stay ( P=0.001). Among support staff, female gender, monthly income, years of primary care service, self-evaluation of unit support function, and PA scores were positively correlated with the score of intention to stay (all P<0.05), while EE score and DP score were negatively correlated with intention to stay (all P<0.05). Conclusions:The intention to stay of PHWs in China during the COVID-19 was at an intermediate level, which was affected by many factors. Among them, job satisfaction was positively correlated with the intention to stay of all occupational categories, and the influencing factors of different occupational categories have some variations.

Diabetic kidney disease(DKD)is the leading cause of end-stage renal disease worldwide and one of the major microvascular complications of diabetes.The pathogenesis of DKD is multifactorial,and its pathological process involves multiple pathways.Ferroptosis is a regulatory cell death characterized by iron dependent lipid peroxidation.Recently,an increasing number of studies have shown that ferroptosis is a key driving factor for the occurrence and development of DKD and has been identified to play a crucial role in the occurrence,development,and treatment of various kidney diseases.Traditional Chinese medicine has unique advantages in preventing and delaying the progression of DKD due to the characteristics of multi-component,multi-target,and multi-pathway.This article focuses on summarizing the impact of key regulatory factors and signaling pathways of ferroptosis on the pathological process of DKD,as well as the research progress of traditional Chinese medicine in regulating ferroptosis key factors and pathways for preventing and treating DKD.The aim of this study is to provide new ideas for the clinical treatment of DKD and the development of new traditional Chinese medicine drugs.

Objective:To investigate the clinical characteristics of patients with combined oxidative phosphorylation deficiency type 4 (COXPD4) related to TUFM gene variation, in order to improve clinicians′ understanding of the disease. Methods:A case of COXPD4 with cystic leukodystrophy admitted to the Children′s Hospital of Zhengzhou University in June 2021 was taken as the study subject, and her clinical characteristics and genetic testing results were retrospectively analyzed. The "combined oxidative phosphorylation deficiency type 4" " TUFM gene" "cystic leukodystrophy" "combined oxidative phosphorylation deficiency 4" "COXPD 4" " TUFM" and "cystic leukodystrophy" were used as keywords, and the documents on COXPD4 related to TUFM gene mutations were reviewed from Wanfang Data Knowledge Service Platform, CNKI, PubMed Document Database, and National Center for Biotechnology Information (NCBI) until August 2021. The COXPD4 patients that have been reported internationally were analyzed for clinical features and variant types. Results:The patient was a 2-month-old girl with clinical manifestations of delayed development and progressive aggravation, elevated lactic acid in serum and cerebrospinal fluid, and diffuse white matter dysplasia with multiple cystic lesions in cerebral magnetic resonance imaging (MRI). Whole exome sequencing showed TUFM gene complex heterozygous variants c.684_684+4delGGTGA and c.1105C>T, which had not been reported in the past. A total of 5 cases of COXPD4 were reported in 4 English literatures. Together with 1 case in this study, there were 4 cases with detailed clinical history data, including 1 male and 3 females. The clinical manifestations were severe early-onset lactic acidosis and developmental lag, and 3 cases were accompanied by progressive infantile encephalopathy. Among them, 3 cases underwent head MRI examination, all of which showed diffuse white matter signal with multiple cystic lesions, 2 cases with basal ganglia involvement and multiple cerebellar gyri deformity. Genetic test indicated different types of TUFM gene variation. Conclusions:COXPD4 is a rare hereditary mitochondrial disease. For cases with COXPD4 clinical and imaging features, TUFM gene mutations can be screened first.

Ferroptosis is a newly discovered non-apoptotic regulatory form of cell death characterized by accumulation of iron-dependent lipid peroxides and reactive oxygen species （ROS）. p53 is a tumor suppressor gene that can induce cell cycle arrest， apoptosis， autophagy， and senescence to maintain genomic stability by mediating transcriptional regulation of a variety of key cellular genes. Recent studies have found that p53 can also regulate ferroptosis bidirectionally by multiple cellular responses including iron metabolism， polyunsaturated fatty acid （PUFAs） metabolism， amino acid metabolism and nicotinamide adenine dinucleotide phosphate （NADPH）-mediated metabolisms， and participate in the pathological progression of diseases such as tumors， nervous system diseases， cardiovascular diseases， liver disease， and kidney disease. This paper provided a systematic review of the mechanism of p53-mediated ferroptosis in the outcome of related diseases and its influencing factors. And the research advance in the mechanisms of targeted regulation of p53-mediated ferroptosis in the prevention and treatment of cancer， stroke， acute ischemic cardiomyopathy， chronic heart failure， atherosclerosis， ulcerative colitis， and adjuvant arthritis by traditional Chinese medicine was also elaborated. This paper was expected to provide new ideas for the prevention and treatment against related diseases.

Objective:To analyze clinical characteristics of cutaneous delayed-type hypersensitivity caused by injection of equine tetanus antitoxin (TAT) or equine anti-tetanus immunoglobulin F (ab′) 2. Methods:Clinical data were collected from 181 outpatients or inpatients with cutaneous delayed-type hypersensitivity caused by injection of equine TAT or anti-tetanus immunoglobulin from 2008 to 2020, and retrospectively analyzed.Results:Before the injection of equine TAT or anti-tetanus immunoglobulin, skin test was negative in 171 (94.47%) of the 181 patients, and the 10 (5.53%) patients with positive skin test responses received desensitization injection. Among the 181 patients, there were 118 males and 63 females aged from 11 to 68 years, with the disease duration of 1 to 7 days and alatency period of 4 to 14 days. There was no significant difference in the clinical manifestations between the patients receiving injection of TAT (130 cases) and those receiving injection of equine anti-tetanus immunoglobulin (51 cases) . Urticaria-like rashes were the main clinical manifestation, and infiltrative erythema occurred at the injection site in 12 patients, of whom 10 developed generalized urticaria all over the body. Of the 181 patients, 163 (90.06%) presented with generalized skin rashes, and 56 (30.94%) had systemic symptoms such as chest tightness, fever, etc, of whom 15 (26.79%) had a history of allergies and 6 with severe symptoms had no history of allergies. Thirty-four (18.78%) patients had single or multiple laboratory abnormalities, such as increased white blood cell counts, elevated C-reactive protein level and urinary glucose, and presence of occult blood in urine. All cases responded well to the treatment with antihistamines and glucocorticoids. The treatment duration ranged from 3 to 10 days, and the outcome was good.Conclusion:TAT-or anti-tetanus immunoglobulin-induced cutaneous delayed-type hypersensitivity may still occur in patients with a negative skin test or after desensitization treatment, and mainly manifests as urticaria-like rashes.

Objective The experiment project was designed to explore the variation of NaI (Tl) gamma spectrometer channels with environmental temperature. ⁶⁰Co and ¹⁵²Eu were used to verify the reliability of the correction methods. Methods Two correction methods were applicated, which were curve fitting correction method and known measurement peak correction method. Results The experimental results showed that temperature changes had an effect on NaI (Tl) measured spectra peak. The relative peak will shift to the right at 5℃ by 9.6%, and to the left at 60℃ by 16%, with the reference temperature set at 25℃. The two methods are based on the channel change due to temperature changes, and they could effectively correct the temperature peak-drift. Conclusion In order to make the measured spectrum information accurate and reliable in field monitoring, it is suggested to monitor the environmental temperature so as to correct the measured data.

Objective: To investigate the diagnostic and predictable value of the levels of serum Trx (S-Trx), urinary Trx (U-Trx) and S-Trx/U-Trx ratio in acute pyelonephritis of children. Methods: A total of 120 children with urinary tract infection were divided into APN group (67 cases) and non-APN group (53 cases).In addition, 67 children with APN were assigned to severe group (23 cases)and non-severe group (44 cases). The leves of serum C-reactive protein(CRP), precalcitonin(PCT), cystatin C (CysC), Trx (S-Trx) and urinary β₂-microglobulin(β₂-MG), neutrophill gelatinase-related apolipoprotein (NGAL), Trx (U-Trx) were collected. Besides, the ratio of S-Trx/U-Trx was also counted. The diagnostic and predictable value of each index were determined by receiver operating characteristic (ROC). Results: Serum PCT, S-Trx, urinary β₂-MG, NGAL, U-Trx was markedly increased and S-Trx/U-Trx ratio was obviously decreased in the APN group compared to that of the non-APN group (P<0.05). Moreover, S-Trx, urinary NGAL, U-Trx was significantly increased and S-Trx/U-Trx ratio was significantly decreased in the severe group compared to that of the non-severe group (P<0.05). Both in APN group or severe APN group, S-Trx and U-Trx displayed significantly positive correlation (P<0.05). The results from ROC demonstrated that AUC were 0.960, and optimal cut-off value were 16.17 μg/L of U-Trx diagnostic APN in children, with a specificity and sensitivity of 94.34% and 92.54%, respectively. The optimal cut-off value was 1.29.AUC of S-Trx/U-Trx 0.960 predicted the severe of APN in children, with a specificity and sensitivity of 81.82% and 82.61%, respectively. Conclusions U-Trx is useful for diagnostic APN in children, S-Trx/U-Trx is an independent predictor of the severe APN.