Key roles of autophagosome/endosome maturation mediated by Syntaxin17 in methamphetamine-induced neuronal damage in mice.

BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the "cargos" mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. RESULTS: Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aß42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. CONCLUSION: Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.

Associations of metformin therapy treatment with endometrial cancer risk and prognosis: A systematic review and meta-analysis.

BACKGROUND: Several abstract studies have demonstrated that metformin may be beneficial for preventing and treating endometrial cancer (EC), while the results have been inconsistent and inconclusive. This systematic review and meta-analysis aimed to investigate the association between metformin use and the incidence and mortality of endometrial cancer in diabetic patients. METHODS: A systematic literature search was performed in Pubmed, EMBASE, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP from inception to November 2022. The outcome measures were hazard ratios (HRs) comparing the EC incidence and mortality in patients with type 2 diabetes mellitus (T2DM) on metformin and non-metformin. A random or fixed-effects model was applied for data analysis, and subgroup analysis was performed to look for factors of heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessed the evidence's certainty. RESULTS: Eleven studies reported data on EC incidence. The pooled results suggested that the use of metformin was associated with a significantly higher incidence of EC (HR = 1.17, 95% CI 1.09-1.26, P < 0.0001). Further, seventeen studies were included for survival analysis. The pooled data showed that metformin could significantly decrease all-cause mortality (HR = 0.62, 95% CI 0.52-0.74, P < 0.00001) and endometrial cancer-specific mortality (HR = 0.95, 95% CI 0.90, 1.00, P = 0.03). Finally, we noted that metformin was associated with significantly improving the progression-free survival (PFS) of EC patients with T2DM (HR = 0.55, 95% CI 0.44, 0.68, P < 0.00001). CONCLUSIONS: This meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could reduce their mortality risk and prolong the progression-free survival time of EC patients with T2DM.

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

Effects of exposure to 3,6-DBCZ on neurotoxicity and AhR pathway during early life stages of zebrafish (Danio rerio).

Polyhalogenated carbazoles (PHCZs) are emerging environmental pollutants, yet limited information is available on their embryotoxicity and neurotoxicity. Therefore, the current work was performed to investigate the adverse effects of 3,6-dibromocarbazole (3,6-DBCZ), a typical PHCZs homolog, on the early life stages of zebrafish larvae. It revealed that the 96-hour post-fertilization (hpf) median lethal concentration (LC50) value of 3,6-DBCZ in zebrafish larvae was determined to be 0.7988 mg/L. Besides, 3,6-DBCZ reduced survival rates at concentrations ≥ 1 mg/L and decreased hatching rates at ≥ 0.25 mg/L at 48 hpf. In behavior tests, it inhibited locomotor activities and reduced the frequency of recorded acceleration states in response to optesthesia (a sudden bright light stimulus) at concentrations ≥ 160 µg/L. Meanwhile, 3,6-DBCZ exposure decreased the frequency of recorded acceleration states in the startle response (tapping mode) at concentrations ≥ 6.4 µg/L. Pathologically, with the transgenic zebrafish model (hb9-eGFP), we observed a strikingly decreased axon length and number in motor neurons after 3,6-DBCZ treatment, which may be ascribed to the activation of the AhR signaling pathway, as evidenced by the molecular docking analysis and Microscale thermophoresis (MST) assay suggested that 3,6-DBCZ binding to AhR-ARNT2 compound proteins. Through interaction with AhR-ARNT, a striking reduction of the anti-oxidative stress (sod1/2, nqo1, nrf2) and neurodevelopment-related genes (elavl3, gfap, mbp, syn2a) were observed after 3,6-DBCZ challenge, accompanied by a marked increased inflammatory genes (TNFß, IL1ß, IL6). Collectively, our findings reveal a previously unrecognized adverse effect of 3,6-DBCZ on zebrafish neurodevelopment and locomotor behaviors, potentially mediated through the activation of the AhR pathway. Furthermore, it provides direct evidence for the toxic concentrations of 3,6-DBCZ and the potential target signaling in zebrafish larvae, which may be beneficial for the risk assessment of the aquatic ecosystems.

Dexmedetomidine administration during brain tumour resection for prevention of postoperative delirium: a randomised trial.

BACKGROUND: Delirium is common, especially after neurosurgery. Dexmedetomidine might reduce delirium by improving postoperative analgesia and sleep quality. We tested the primary hypothesis that dexmedetomidine administration during intracerebral tumour resection reduces the incidence of postoperative delirium. METHODS: This randomised, double-blind, placebo-controlled trial was conducted in two tertiary-care hospitals in Beijing. We randomised 260 qualifying patients to either dexmedetomidine (n=130) or placebo (n=130). Subjects assigned to dexmedetomidine were given a loading dose of 0.6 µg kg-1 followed by continuous infusion at 0.4 µg kg-1 h-1 until dural closure; subjects in the placebo group were given comparable volumes of normal saline. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method twice daily during the initial 5 postoperative days. RESULTS: The average (standard deviation) age of participating patients was 45 (12) yr, duration of surgery was 4.2 (1.5) h, and patients assigned to dexmedetomidine were given an average of 126 (45) µg of dexmedetomidine. There was less delirium during the initial 5 postoperative days in patients assigned to dexmedetomidine (22%, 28 of 130 patients) than in those given placebo (46%, 60 of 130 patients) with a risk ratio of 0.51 (95% confidence interval: 0.36-0.74, P<0.001). Postoperative pain scores with movement, and recovery and sleep quality were improved by dexmedetomidine (P<0.001). The incidence of safety outcomes was similar in each group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduced by half the incidence of delirium during the initial 5 postoperative days in patients recovering from elective brain tumour resection. CLINICAL TRIAL REGISTRATION: NCT04674241.

Large-scale surface water-groundwater origins and connectivity in the Ordos Basin, China: Insight from hydrogen and oxygen isotopes.

The sustainability of water resources is a major challenge for the Ordos Basin and Loess Plateau of China. The basis of effective water management is an understanding of the water cycle process. This study investigated the surface water-groundwater origins and connectivity using stable isotopes (δD and δ18O) of surface water and groundwater in 11 river basins in the Ordos Basin. It was found that the surface water-groundwater origins and hydraulic connection were characterized by regional differences, mainly induced by climatic characteristics, hydrogeological conditions and human activities. Specifically, the impact of thick loess deposits caused surface water and groundwater to take long time to produce a hydraulic connection. In contrast, areas with thin loess deposits and frequent human activities showed a good connectivity between surface water and groundwater. As for water origins, summer precipitation was a common source of surface water and groundwater in the study area, and groundwater discharge was another source of surface water. However, surface water and groundwater were subjected to different degrees of evaporation during receiving precipitation recharge. Notably, thick loess deposits had an impact on groundwater evaporation because both the recharge of precipitation to groundwater and the discharge of groundwater to surface water took a long time. In addition, it was found that frequent human activities (mining, irrigation and urban construction) could weaken the impact of evaporation. This large-scale analysis provided new insights into the origins and connectivity of surface water and groundwater in areas with thick unsaturated zones for water resources management.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study.

BACKGROUND: This prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy. METHODS: A total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. CONTROL GROUP: 83 patients received EC-TH regimen. The chi-square test, Fisher's exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs). RESULTS: In the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred. CONCLUSION: The efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

Element-Doped Mxenes: Mechanism, Synthesis, and Applications.

Heteroatom doping can endow MXenes with various new or improved electromagnetic, physicochemical, optical, and structural properties. This greatly extends the arsenal of MXenes materials and their potential for a spectrum of applications. This article comprehensively and critically discusses the syntheses, properties, and emerging applications of the growing family of heteroatom-doped MXenes materials. First, the doping strategies, synthesis methods, and theoretical simulations of high-performance MXenes materials are summarized. In order to achieve high-performance MXenes materials, the mechanism of atomic element doping from three aspects of lattice optimization, functional substitution, and interface modification is analyzed and summarized, aiming to provide clues for developing new and controllable synthetic routes. The mechanisms underlying their advantageous uses for energy storage, catalysis, sensors, environmental purification and biomedicine are highlighted. Finally, future opportunities and challenges for the study and application of multifunctional high-performance MXenes are presented. This work could open up new prospects for the development of high-performance MXenes.

Epidural Anesthesia-Analgesia and Recurrence-free Survival after Lung Cancer Surgery: A Randomized Trial.

BACKGROUND: Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia-analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. METHODS: Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural-general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. RESULTS: Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural-general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural-general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural-general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). CONCLUSIONS: Epidural anesthesia-analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm.

Thoracic Paravertebral Blockade Reduces Chronic Postsurgical Pain in Breast Cancer Patients: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery. DESIGN: A randomized controlled trial with two parallel groups. SETTING: A tertiary hospital. METHODS: Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery. RESULTS: A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28-0.96, P = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P = 0.006 and P < 0.001, respectively). The percentages of patients with neuropathic pain were also lower in the PVB group than the control group at both six and 12 months after surgery (P = 0.016 and 0.028, respectively). Adverse events did not differ between groups. CONCLUSIONS: For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery.

Investigation of the differences between the medical personnel's and general population's view on the doctor-patient relationship in China by a cross-sectional survey.

BACKGROUND: Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients' medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP). METHODS: This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. A total of 154 MP and 329 GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon's Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data. RESULTS: Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical staff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP's preference for their children's practice (p < 0.05). Most MPs hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR. CONCLUSION: The MP's and GP's views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.

Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.

[Anti-radiation effect and mechanism studies of ethanol extracts from Spatholobus suberectus and its active component catechin].

To study the anti-radiation effect and mechanism of ethanol extracts from Spatholobus suberectus and its active component catechin, ICR mice were exposed to 6Gy irradiation and randomly divided into normal group, model group, positive control group (amifostine, 43.6 mg•kg⁻¹, iv 30 min before irradiation), SSD group (10, 20, 40 g•kg⁻¹) and catechin group (50, 100, 200 mg•kg⁻¹). The mice were administered the appropriate drugs once a day after irradiation for 28 consecutive days. Blood samples were collected from the tail end and the number of peripheral blood cells was counted before irradiation and on day 1, 3, 7, 14, 21 and 28 using a microcell counter. Changes of thymus and spleen index of mice on day 7 were observed. The serum SOD, GSH-Px activity and MDA level were detected by the colorimetric method. The colony forming ability of bone marrow hematopoietic progenitor cells on day 7 was detected by semi solid culture method. The HE staining was adopted to observe the pathological changes. The apoptosis of bone marrow cells was detected by flow cytometry. The expression of cleaved caspase-3 and Bax of bone marrow cells were measured separately by western-blotting and immunohistochemistry method. SSD and catechin can both significantly revert the irradiated-induced decline in hematological parameters (RBC, WBC, PLT, Hb), improve thymus and spleen index, significantly enhance serum SOD and GSH-Px activity and decrease the MDA level. The proliferation and differentiation of hematopoietic progenitor cells in bone marrow were promoted, the apoptosis of bone marrow cells was significantly up-regulated and the expression of cleaved caspase-3 and Bax was significantly reduced in SSD and catechin group. SSD and catechin have significant anti-radiation effect and its mechanism may be related to hematopoietic promoting, antioxidant and anti-apoptotic effects.

[Effect of six class of Kaixin San formulas on pharmacological and preliminary mechanism of Alzheimer's disease mice].

The efficacy of Chinese herbal formulas in treating Alzheimer has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on learning and memory decline, brain-derived neurotrophic factor (BDNF) in the hippocampus, tau protein, acetylcholinesterase (AChE) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Kunming mice were selected and established a mouse model of Alzheimer's by intraperitoneal injection of D-galactose and sodium nitrite, continued intragastric 4 weeks, using the ability of learning and memory in Morris water maze test to evaluate the animals in each group; the content of BDNF in the hippocampus of mice with Western blotting detected; ELISA method for the detection of each group of mice hippocampal tau protein,p-Tau protein, Aß,Ach,AchE and serum NT-proBNP levels. The results showed that, Kaixin San of Qianjin Yaofang three dose recorded significantly improved learning and memory ability of mice; increased the content of BDNF and Ach in the hippocampus; decreased the content of Aß, Tau protein, p-Tau protein in the hippocampus; high, middle dose significantly decreased the serum NT-proBNP and AchE in hippocampus, the effect is most significant. Part dose of Kaixin San of Yixin Fang, Kaixin Wan of Yimen Fang, Dingzhi Xiaowan of Beji Qianjin Yaofang and Dingzhi Wan of Guji Luyan could improve the learning and memory ability evaluation indicators, significantly increased BDNF and Ach in the hippocampus of AD model mice, reduced the Aß, Tau protein, p-Tau protein in hippocampus of AD model mice, decreased the NT-proBNP and AchE in serum of AD mice, the effect is more significant. Three does of Buxin Tang of Qianjin Yi had no effects of treatment in Alzheimer's disease. The results showed the treatment in AD of Kaixin San of Qianjin Yaofang is the most significant.

Attitude, knowledge, and barriers of Chinese clinical and nursing students in implementing complementary and alternative medicine for COVID-19：a cross-sectional study.

Background: Complementary and alternative medicine (CAM) has emerged to combat the global COVID-19 pandemic. However, no studies have been conducted to evaluate the attitudes, knowledge, and barriers of Chinese clinical and nursing students in implementing CAM during this period. Objective: The aim of this study was to investigate the attitude, knowledge, and barriers of Chinese clinical and nursing students in using CAM in the context of COVID-19. Methods: An online-based cross-sectional survey was carried out among Chinese medical students, majoring in clinical medicine or nursing, in Nanjing, Jiangsu Province, and Zhengzhou, Henan Province from May to July 2022. A total of 402 clinical and 644 nursing students responded to a self-administered questionnaire through the Questionnaire Star and WeChat APPs. SPSS 25 (version 25) was used for data analysis. Proportions were compared by Chi-square test. Level of significance between groups was analyzed using independent student t-test and Mann-Whitney U test. Results: The average score of attitude was 46.63 (SD: 7.38) in clinical students and 49.84 (SD: 6.76) in nursing students. The top four most commonly used CAM treatments in China were proprietary Chinese medicine, diet therapy, decoction, and acupuncture and moxibustion (59.66 %, 22.28 %, 11.66 %, 9.85 %). The students had a good mastery of knowledge about CAM-based prevention and control of COVID-19 (mean score 7.36). The score of CAM knowledge in nursing students was significantly higher than that in clinical students (7.56 VS 7.04, P = 0.000). Gender, grade, previous use, age, and knowledge score could affect students' attitude towards CAM. The main barriers in spreading CAM use included time-consumption, bad taste, and fear of treatment-related pain (24.5 %). Compared with clinical students, nursing students were more likely to recommend CAM to patients in the future (P = 0.002). Conclusions: During the COVID-19 pandemic, nursing students were more positive towards CAM use, had a better mastery of CAM knowledge than clinical students. CAM is expected to provide better outcomes in COVID-19 patients. Future studies should focus on the changes in students' attitudes over time and exploration of influencing factors on CAM use.

Design, Synthesis and Preliminary Bioactivity Evaluation of N-Acetylcysteine Derivatives as Antioxidative and Anti-Inflammatory Agents.

N-acetylcysteine (NAC) is a commonly used mucolytic agent and antidote for acetaminophen overdose. For pulmonary diseases, NAC exhibits antioxidative properties, regulates cytokine production, reduces apoptosis of lung epithelial cells, and facilitates the resolution of inflammation. However, the efficacy of NAC in clinical trials targeting different pathological conditions is constrained by its short half-life and low bioavailability. In the present study, a series of NAC derivatives were designed and synthesized to further enhance its pharmacological activity. Structure-activity relationship (SAR) studies were conducted to optimize the activating groups. In vitro evaluations revealed that compounds 4 r, 4 t, 4 w, and 4 x exhibited superior antioxidative and anti-inflammatory activities compared to the positive controls of NAC and fudosteine. The ADME prediction analysis indicated that these compounds exhibited a favorable pharmacological profile. In-vivo experiments with compound 4 r demonstrated that the high-dose group (80 mg/kg) exhibited improved therapeutic effects in reversing the HPY level in mice with pulmonary fibrosis compared to the NAC group (500 mg/kg), further proving its superior oral bioavailability and therapeutic effect compared to NAC.

Multi-isotopes (δD, δ18Owater, 87Sr/86Sr, δ34S and δ18Osulfate) as indicators for groundwater salinization genesis and evolution of a large agricultural drainage lake basin in Inner Mongolia, Northwest China.

Groundwater salinization, a major eco-environmental problem in arid and semi-arid areas, can accelerate soil salinization, reducing crop productivity and imbalances in ecosystem diversity. This study classified water samples collected from the Ulansuhai Lake basin into five clusters using self-organizing maps (SOM). On this basis, multiple isotopes (δ18Owater, δD, 87Sr/86Sr, δ18Osulfate and δ34S) and isotopic models (Rayleigh fractionation and Bayesian isotope mixing models) were used to identify and quantify the genesis and evolution of groundwater salinization. The results showed that the samples were brackish or saline water, and the hydrochemical types were dominated by Na + K-Cl (SO4). It has been proved that the processes associated with groundwater salinization in the Ulansuhai Lake basin were dominated by water-rock interaction and human inputs. Among them, evaporite dissolution contributed substantially to groundwater salinity. Furthermore, salt inputs from human activities cannot be negligible. Based on the model calculations, evaporite dissolution accounted for the most significant proportion of all sources, with a mean value of 53 %. In addition, human inputs from regular agricultural activities (28 % from sewage and manure and 8 % from fertilizers) constituted another vital source of groundwater salinization associated with extensive agricultural activities in the study area. This study's results can deepen our understanding of the genesis of groundwater salinization and the evolution of the agricultural drainage lake basin. This knowledge will assist the Environmental Protection Department in developing effective policies for groundwater management in the Yellow River Basin.

Four-Component Radical 1,2-Selenosulfonylation of Allenes.

Selenosulfones, as pivotal pharmaceutical molecule frameworks, have become a research hotspot in modern organic synthesis due to their vital need for efficient preparation. Herein, we have developed an iron-catalyzed four-component controllable radical tandem reaction of allenes involving cycloketone oxime esters, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and diphenyl diselenides for the synthesis of complex selenosulfones. This is the first case of achieving the 1,2-selenosulfonylation of allenes via a radical process, wherein precise control of radical rates and polarity matching enhance high regioselective conversion. The reaction conditions are ecofriendly and mild with step-efficiency by forming two new C-S bonds and one C-Se bond in one pot. Moreover, the 1,2-selenosulfonylation of allenes can be achieved by replacing cycloketone oxime esters with aryldiazonium tetrafluoroborates in this system.