OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

This paper summarizes the experience of professor DING Yuanqing in treating post-stroke depression （PSD） of young and middle-aged patients with the method of regulating qi and promoting blood circulation. PSD is a syndrome resulting by vascular injury and impairment of brain marrow and vital activity after the stroke. Factors such as poor lifestyle， improper control of chronic diseases and sleep disorders，etc.，which can be harmful individually， or they can interact. Over time，these factors can block yang of defensive qi，obstract blood circulationg and disturb qi movement. Reverse ascending of defensive qi can generate wind and fire，generate phlegm and stasis from the fluid the blood. Qi stagnation， phlegm and stasis can combined with stagnation heat， phlegm heat， blood stasis heat which caused by stroke ， which can further aggravate pulse accumulation， damage the blood vessels and block the collaterals. Consequently， defensive qi is floating over and nutrient qi is not smooth， resulting in inadequate nourishment of the brain marrow，and disfunction of vital activity， causing depressive symptoms. Professor DING innovatively applied the method of regulating qi and promoting blood circulation. He selected the classic prescriptions such as Guizhi Decoction（桂枝汤）， Baoyuan Decoction（保元汤）， as well as self-fitting prescriptions like Erdan Decoction（二丹汤）， Erzhu Decoction（二竹汤）， to relieve qi and tonify qi，promote harmonious blood circulation， facilitate vasodilation， ease symptoms of depression， invigorate the mind， and provide an effective treatment for PSD.

BACKGROUND:Ferroptosis is strongly associated with the occurrence and progression of osteoarthritis,but the specific characteristic genes and regulatory mechanisms are not known. OBJECTIVE:To identify osteoarthritis ferroptosis signature genes and immune infiltration analysis using the WGCNA and various machine learning methods. METHODS:The osteoarthritis dataset was downloaded from the GEO database and ferroptosis-related genes were obtained from the FerrDb website.R language was used to batch correct the osteoarthritis dataset,extract osteoarthritis ferroptosis genes and perform differential analysis,analyze differentially expressed genes for GO function and KEGG signaling pathway.WGCNA analysis and machine learning(random forest,LASSO regression,and SVM-RFE analysis)were also used to screen osteoarthritis ferroptosis signature genes.The in vitro cell experiments were performed to divide chondrocytes into normal and osteoarthritis model groups.The dataset and qPCR were used to verify expression and correlate immune infiltration analysis. RESULTS AND CONCLUSION:(1)12 548 osteoarthritis genes were obtained by batch correction and PCA analysis,while 484 ferroptosis genes were obtained,resulting in 24 differentially expressed genes of osteoarthritis ferroptosis.(2)GO analysis mainly involved biological processes such as response to oxidative stress and response to organophosphorus,cellular components such as apical and apical plasma membranes,and molecular functions such as heme binding and tetrapyrrole binding.(3)KEGG analysis exhibited that differentially expressed genes of osteoarthritis ferroptosis were related to signaling pathways such as the interleukin 17 signaling pathway and tumor necrosis factor signaling pathway.(4)After using WGCNA analysis and machine learning screening,we obtained the characteristic gene KLF2.After validation by gene microarray,we found that the gene expression of KLF2 was higher in the test group than in the control group in the meniscus(P=0.000 14).(5)In vitro chondrocyte assay showed that type Ⅱ collagen and KLF2 expression was lower in the osteoarthritis group than in the control group in chondrocytes(P<0.05),while in osteoarthritis ferroptosis,mast cells activated was closely correlated with dendritic cells(r=0.99);KLF2 was closely correlated with natural killer cells(r=-1,P=0.017)and T cells follicular helper(r=-1,P=0.017).(6)The findings indicate that using WGCNA analysis and machine learning methods confirmed that KLF2 can be a characteristic gene for osteoarthritis ferroptosis and may improve osteoarthritis ferroptosis by interfering with KLF2.

Objective:To construct machine learning-based delirium prediction models for ICU patients with multiple trauma and evaluate their prediction efficiency.Methods:A retrospective case-control study was conducted to analyze the clinical data of 417 ICU multiple trauma patients admitted to the First Affiliated Hospital of Zhengzhou University from July 2019 to June 2022, including 305 males and 112 females, aged 18-88 years [(47.8±15.7)years]. The score of acute physiology and chronic health status assessment II (APACHE II) was 0-50 points [(9.80±0.29)points]. The patients were randomly divided into training set ( n=291) and test set ( n=126) with a ratio of 7∶3. The demographic data, past history, treatment and laboratory results of the patients were collected. Lasso regression analysis was applied to screen variables that were significantly correlated to the incidence of delirium in the training set and the variables were then included into the machine learning models. Six machine learning methods including the random forest, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor were used to construct the delirium prediction models for ICU multiple trauma patients. The accuracy, sensitivity, precision, F1 fraction and area under the curve (AUC) of the receiver′s operating characteristics (ROC) curve were calculated by using the data in the test set to evaluate the prediction efficiency of the models. Results:With regards to the six prediction models, namely random forests, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor prediction models, the accuracy in the test set was 0.70, 0.68, 0.69, 0.73, 0.70 and 0.60 respectively; the sensitivity was 0.74, 0.80, 0.81, 0.86, 0.85 and 0.69 respectively; the precision was 0.72, 0.69, 0.70, 0.73, 0.71 and 0.65 respectively; the F1 fraction was 0.73, 0.74, 0.75, 0.79, 0.78 and 0.67 respectively; the AUC was 0.72, 0.73, 0.72, 0.80, 0.74 and 0.64 respectively. Among them, the logistic regression model had the best discriminability.Conclusion:Delirium prediction models for ICU patients with multiple trauma have been successfully constructed, among which the logistic regression model has the best prediction efficiency and can serve as an effective tool for early prediction and prevention of delirium in the clinical care of patients with multiple trauma.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.

OBJECTIVE: To explore the genetic basis for fetuses with renal anomalies. METHODS: Genomic DNA of four fetuses and their parents was extracted from amniotic fluid and peripheral blood samples and subjected to whole genome sequencing. Candidate variants were predicted according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by SNP-array and Sanger sequencing. RESULTS: Two fetuses were found to carry a 1.45 Mb pathogenic microdeletion in 17q12 and a pathogenic 1.85 Mb microduplication at 1q21.1-21.2, respectively. One fetus was found to harbor compound heterozygous variants c.8301del (p.Asn2768Thrfs*18) and c.4481del (p.Asn1494Thrfs*6) of the PKHD1 gene, which were predicted to be pathogenic. And one fetus has harbored homozygous c.1372dup (p.Thr458Asnfs*5) variants of the BBS12 gene, which was predicted to be likely pathogenic. All variants were validated by Sanger sequencing. CONCLUSION Whole genome sequencing can enable efficient prenatal diagnosis for fetuses with renal anomalies with high accuracy.
Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Whole Genome Sequencing

Objective To investigate job satisfaction and influencing factors of medical staff in China.Methods From December 2017 to January 2018, based on the third round third-party evaluation of the Healthcare Improvement Initiative, data on job satisfaction of medical staff at 136 tertiary public hospitals in 31 provinces of China were collected.Chi-square test and binary multivariate logistic regression were used to analyze the influencing factors of job satisfaction.Results The job satisfaction of medical staff at 136 sample hospitals was relatively low. 34.6% of the doctors were satisfied with their job, while the corresponding rate in the nurses was 48.7%. Multi-factor analysis showed that income level, workload, doctor-patient relationship, hospital′s compensation policy, and promotion policy were all significant factors influencing medical staff′s job satisfaction ( workload OR <1, remaining variables OR >1, P <0.05 ). Conclusions Improvement of the medical staff′s job satisfaction depends on optimizing their income distribution policy, increasing their income, improving the promotion policy of professional titles, reducing their workload rationally and building a harmonious relationship between doctors and patients.

Objective: To investigate the effect of NACHT-LRR-PYD- containing proteins 3 (NLRP3) mediated pyroptosis in myocardial cells undergoing hypoxia/deoxygenation (H/R) injury. Methods: In order to observe whether H/R-treatment could cause pyroptosis, H9c2 cells were divided into 2 groups randomly using the lottery method: control group(without H/R-treatment) and H/R group (in which the H9c2 cells were underwent H/R-treatment). In order to clarify the role of pyroptosis in H/R-injury, H9c2 cells were divided into 4 groups randomly using the lottery method: control group(in which the H9c2 cells were cultivated with normal medium); YVAD group(in which the H9c2 cells were pretreated with z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-YVAD-FMK) 20 μm for 4 hours, then replaced with normal medium); H/R group(H9c2 cells underwent H/R-treatment); YVAD+H/R group (in which the H9c2 cells were pretreated with 20 μm Z-YVAD-FMK for 4 hours before H/R-treatment). To determine whether H/R-induced cell pyroptosis is associated with NLRP3, H9c2 cells were divided into 4 groups randomly using the lottery method: control group (in which cells were transfected with a control nonspecific siRNA); si-NLRP3 group (in which cells were transfected with NLRP3-targeting siRNA); H/R group(in which cells were transfected with a control nonspecific siRNA before H/R-treatment); si-NLRP3+H/R group(in which the H9c2 cells were transfected with NLRP3-targeting siRNA before H/R-treatment). Pore formation on cell membrane was detected by propidium iodide (PI) staining. Cell viability was detected by CCK8 reagent. The protein expression of Caspase-1, interleukin-1β (IL-1β) and NLRP3 was detected by Western blot. Results: (1) The positive rate of PI staining ((26.46±5.15)% vs. (1.69±0.73)%,P<0.01), expression of NLRP3 (0.57±0.16 vs. 0.23±0.06,P<0.01), expression of Caspase-1 (1.07±0.13 vs. 0.37±0.08,P<0.01), and expression of IL-1β (0.38±0.08 vs. 0.16±0.05,P<0.01) were significantly higher in H/R group than in control group. (2)The cell vitality was significantly higher in YVAD+H/R group than in H/R group ((87.31±9.05)% vs. (73.30±7.19)%, P<0.05).The positive rate of PI staining was significantly decreased in YVAD+H/R group than in H/R group ((18.12±4.36)% vs. (26.45±4.60)%, P<0.05). The expression of Caspase-1 (0.72±0.12 vs. 1.07±0.15, P<0.05) and IL-1β(0.29±0.07 vs. 0.39±0.06, P<0.05) were significantly lower in YVAD+H/R group than in H/R group. (3) The cell vitality was significantly increased in si-NLRP3+H/R group than in H/R group ((85.46±7.71)% vs. (72.41±5.53)%, P<0.05). The positive rate of PI staining was significantly lower in si-NLRP3+H/R group than in H/R group ((18.22±4.20)% vs. (26.73±3.26)%, P<0.05). The expression of Caspase-1(0.87±0.07 vs. 1.15±0.15, P<0.05) and IL-1β(0.41±0.07 vs. 0.58±0.10, P<0.05) were significantly decreased in si-NLRP3+H/R group than in H/R group. Conclusion NLRP3 mediated pyroptosis is involved in H/R injury of myocardial cells.