Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

OBJECTIVE Nowadays, the development of pharmacy discipline has a new trend, which is reflected in the close connection with the national strategy, the integration of basic and applied research, the high degree of discipline intersection, the long achievement cycle, and the high career access, etc. The traditional model of pharmacy talent cultivation can no longer meet the needs of the development of pharmacy discipline and the creation of new drugs in the new era, therefore, it puts forward new paths of the cultivation of innovative talents in pharmacy. METHODS On the basis of analyzing the main problems existing in the process of cultivation of existing pharmacy talents, to describe the new trends and new paths of cultivation of top-notch innovative pharmacy talents in the new era. RESULTS Propose to start from the four aspects of the trinity of the guidance mechanism, the mechanism of the science education and human resources mechanism, the regularization of the joint mechanism, and the mechanism of the cultivation of talents. CONCLUSION It is proposed to build a talent cultivation model with a "Student-Scholar" orientation, to provide new ideas for the cultivation of future pharmacy talents in the new era.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

OBJECTIVE In the context of the era of innovation and entrepreneurship, the training model of pharmaceutical talents is facing challenges. In order to cultivate overall development of pharmaceutical innovative talents, an in-depth research is carried out from multiple perspectives such as education orientation, education mode and education team. METHODS The research systematically analyzed the concept, system, orientation, channels, plan and cooperation of pharmaceutical talent training to build a new cultivation mechanism which adapts to the national strategic adjustments and social situation changes. RESULTS The research summarized the ideas and formulated a model for cultivating innovative application-oriented pharmaceutical talents which was guided by ideological and political education, oriented towards real issues in the industrial, scientific, and clinical sectors. It emphasized multi-chain collaboration, integrating high-quality resources to promote the enhancement of original innovation capabilities. CONCLUSION The research not only provides experience for the training of pharmaceutical innovative talents in the College of Pharmaceutical Sciences of Zhejiang University, but also provides references for the training of pharmaceutical talents in other universities in China.

OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency （POI） rats and its potential mechanism based on stromal cell-derived factor-1 （SDF-1）/CXC subfamily receptor 4 （CXCR4） axis. METHODS POI rat model was established by intraperitoneal injection of vinylcyclohexene （VCD）. The successfully modeled rats were randomly divided into model group， cryptotanshinone low-dose group （50 mg/kg）， cryptotanshinone high-dose group （100 mg/kg）， and cryptotanshinone high-dose+AMD3100 group （100 mg/kg cryptotanshinone+2.5 mg/kg CXCR4 inhibitor AMD3100）， with 10 rats in each group. Another 10 rats were injected with normal saline instead of VCD as the control group. Rats in each drug group were given intragastrical or （and） intraperitoneal injection of the corresponding drug once a day for 4 weeks. The levels of estradiol （E2）， luteinizing hormone （LH） and follicle-stimulating hormone （FSH） in serum and reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in ovarian tissue were detected in each group. The morphology of ovarian tissue was observed. The cell apoptosis of ovarian tissue， as well as the mRNA expressions of SDF-1， CXCR4 and the protein expressions of caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， SDF- 1， CXCR4 were detected. RESULTS Compared with the control group， the ovarian atrophied， the number of primitive follicles decreased， the number of atretic follicles increased， and the damage was obvious in the model group. Serum E2 level， SOD and GSH-Px levels in ovarian tissue， the mRNA expressions of SDF-1 and CXCR4， and the protein expressions of Bcl-2， SDF-1 and CXCR4 in ovarian tissue were all significantly decreased or down-regulated； the levels of FSH and LH in serum， ROS and MDA levels in ovarian tissue， the cell apoptosis rate， and the protein expressions of caspase-3 and Bax in ovarian tissue mail：k26awn@163.com were increased or upregulated significantly （P＜0.05）. Compared with model group， the ovarian tissue lesions of rats in cryptotanshinone low-dose and high-dose groups were significantly improved， and each quantitative index was significantly improved （P＜0.05）. AMD3100 could significantly reverse the improvement effect of cryptotanshinone on the above indexes （P＜0.05）. CONCLUSIONS Cryptotanshinone can reduce ovarian cell apoptosis and oxidative stress in POI rats by activating the SDF-1/CXCR4 axis， regulating serum hormone levels， thereby improving ovarian injury.

Objective:To investigate the feasibility of predicting the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth by transabdominal-transvaginal ultrasound cervical length sequential screening in the second trimester.Methods:This prospective longitudinal cohort study included singleton pregnant women at 11-13 +6 gestational weeks who were admitted to Nanjing Drum Tower Hospital from January 2023 to September 2023. Transabdominal and transvaginal cervical lengths were measured during the mid-trimester fetal ultrasound scan at 18-24 weeks, and pregnancy outcomes were obtained after delivery. A short cervix was defined as a transvaginal cervical length of ≤25 mm, and the outcomes were defined as spontaneous preterm birth occurs between 20 and 36 +6 weeks and extremely preterm birth before 32 weeks. The area under the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of predicting spontaneous preterm birth by transabdominal and transvaginal cervix length, as well as the effectiveness of predicting short cervix by transabdominal cervical length. The relationship between transabdominal and transvaginal cervical length was evaluated using a scatter plot. Results:A total of 562 cases were included in this study, comprising 33 cases of spontaneous preterm birth (7 cases occurring before 32 weeks) and 529 cases of term birth. (1) Compared to the term birth group, transabdominal cervical length (median: 37.6 vs 33.2 mm; Z=-3.838, P<0.001) and transvaginal cervical length (median: 34.0 vs 29.9 mm, Z=-3.030, P=0.002) in the spontaneous preterm birth group were significantly shorter. (2) The areas under the ROC curve for predicting spontaneous preterm birth by transabdominal and transvaginal cervical length were 0.699 (95% CI: 0.588-0.809) and 0.657 (95% CI: 0.540-0.774), respectively. The sensitivity, specificity and positive predictive value of transvaginal cervical length Conclusions:In singleton pregnancy women with low risk of preterm birth, transabdominal-transvaginal cervical length sequential screening can reduce unnecessary transvaginal ultrasounds by approximately 41% without missing the diagnosis of pregnant women with a short cervix. This method also enhances the effectiveness of transvaginal cervical length to spontaneous preterm birth.

Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

Objective: To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage. Methods: The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration. Results: The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug. Conclusion Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

To analyze the clinical features and genetic variants of a child with type 4 familial partial lipodystrophy (FPLD4) and the initial manifestation of diabetes.The male patient with the age of 13 years and 5 months, and the diabetes course was about 3 years, the patient was admitted to Children′s Hospital of Soochow University on November 10, 2021(4 th hospitalization at the hospital), in the course of diabetes, the children repeatedly suffered from diabetes ketoacidosis, and lipid metabolism complications gradually emerged.The gene sequencing showed that the proband and his mother carried dual gene mutations of PLIN1 c. 1325delG(p.G442Afs*99) and SPINK1 c. 194+ 2T>C(p.? ). The PLIN1 gene was the causal gene of FPLD4.The mutations of c. 1325delG in the PLIN1 gene had not been previously reported.Based on the clinical phenotype, family history and genetic testing findings, the patient was diagnosed as FPLD4.In addition, the mutation of SPINK1 c. 194+ 2T>C(p.? ) might increase the risk of chronic pancreatitis.This case report enriched the clinical characteristics and genotype data of FPLD4.Gene sequencing assisted the accurate diagnosis of the type of diabetes.The effects of dual gene mutations on disease progression should be concerned, which were of great significance to develop treatment regimen and disease management.

Abnormal iron metabolism mediated by ferritinophagy is one of the most important mechanisms in the occurrence of ferroptosis.The regulatory mechanism of ferritinophagy mainly involves the transcription of NCOA4 and its corresponding protein modifications.Ferroptosis plays an important role in the development of colitis and colitis-associated cancer,and target-oriented regulation of ferroptosis can alleviate colonic inflammatory response and induce the tumor cell death.This article mainly reviewed the regulatory mechanism of NCOA4-mediated ferritinophagy and its progress in colitis and colitis-related cancer,which may provide a new point for the investigation on mechanism of colitis and inflammation-cancer transformation.