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Abstract Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well as materials science, a direct meta-selective C–H functionalization of pyridines is of paramount importance, but such reactions remain limited and highly challenging. In general, established methods for meta C–H functionalization of pyridines rely on the utilization of tailored electrophilic reagents to realize the intrinsic polarity match. Herein, we report a complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation of pyridines through a redox-neutral dearomatization-rearomatization strategy by a tandem dearomative cycloaddition/hydrogen-evolution electrooxidative C–H sulfonation of the resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, and facile late-stage modification, have been demonstrated, which further contributes to the practicality and adaptability of this approach.

The initial stages of acute pancreatitis (AP) are characterized by a significant event - acinar ductal metaplasia (ADM). This process is a crucial feature of both acute and chronic pancreatitis, serving as the first step in the development of pancreatic cancer. Ion channels are integral transmembrane proteins that play a pivotal role in numerous biological processes by modulating ion flux. In many diseases, the expression and activity of ion channels are often dysregulated. Metal ions, including calcium ions (Ca2+), ferrous ions (Fe2+), and Copper ions (Cu2+), assume a distinctive role in cellular metabolism. These ions possess specific biological properties relevant to cellular function. However, the interactions among these ions exacerbate the imbalance within the intracellular environment, resulting in cellular damage and influencing the progression of AP. A more in-depth investigation into the mechanisms by which these ions interact with acinar cells is essential for elucidating AP’s pathogenesis and identifying novel therapeutic strategies. Currently, treatment for AP primarily focuses on pain relief, complications prevention, and prognosis improvement. There are limited specific treatments targeting acinous cell dedifferentiation or ion imbalance. This study aims to investigate potential therapeutic strategies by examining ion crosstalk within acinar cells in the context of acute pancreatitis.

Introduction: Mechanical ventilation after respiratory insufficiency can induce diaphragm dysfunction through various hypothesized mechanisms. In this study, we evaluated the rehabilitative effect of acupuncture on diaphragm function in patients with respiratory insufficiency using meta-analysis and summarised the rules of acupoints through association rules analysis. Methods: Articles (published from January 2000 to February 2024) were retrieved from the following databases: PubMed, Cochrane Library, Embase, Web of Science, CNKI, VIP, SinoMed, and Wanfang. Two researchers conducted literature selection, data extraction, and statistical analysis independently. The risk of bias was assessed utilizing the Physical Therapy Evidence Database (PEDro) scale. The meta-analysis was performed with RevMan 5.4 software, and the quality of each outcome evidence was assessed via the online software GRADEpro GDT. The regularity of acupoint selection was summarized using association rules analysis. This study is registered on PROSPERO, number CRD42024526705. Results: Eleven articles were eventually included, all of which were of low to moderate quality. Results of the meta-analysis showed a significant increase in diaphragmatic thickening fraction (MD 3.40 [1.52, 5.27]) and diaphragmatic excursion (MD 0.95 [0.58, 1.31]) in patients with respiratory insufficiency after acupuncture treatment. Also, OI (MD 28.52 [15.93, 41.11]) and PaO2 (MD 7.18 [2.22, 12.13]) were significantly elevated and PaCO2 (MD −6.94 [-12.30, −1.59]) was decreased. Mechanical ventilation time (MD-1.86 [-2.28, −1.45]) was also significantly improved. The overall quality of the outcome evidence is deemed moderate. Association rules analysis showed that ST36, RN4, RN6, and others are core acupoints for the treatment of diaphragmatic dysfunction in patients with respiratory insufficiency by acupuncture. Conclusion: Acupuncture shows potential in the rehabilitation of patients with respiratory insufficiency and may serve as a complementary and alternative therapy for related conditions. We suggest the use of ST36 as a core acupoint, in combination with other acupoints. Due to the potential publication bias and high heterogeneity of the current data, further high-quality RCTs are needed to confirm these findings.

Objectives Following the implementation of China’s open policy with respect to COVID-19 on 7 December 2022, the influx of patients with infectious diseases has surged rapidly, necessitating hospitals to adopt temporary requisition and modification of ward beds to optimise hospital bed capacity and alleviate the burden of overcrowded patients. This study aims to investigate the effect of an intensive care unit (ICU) bed capacity optimisation method on the average length of stay (ALS) and average cost of hospitalisation (ACH) after the open policy of COVID-19 in China.Design and setting A difference-in-differences (DID) approach is employed to analyse and compare the ALS and ACH of patients in four modified ICUs and eight non-modified ICUs within a tertiary hospital located in southwest China. The analysis spans 2 months before and after the open policy, specifically from 5 October 2022 to 6 December 2022, and 7 December 2022 to 6 February 2023.Participants We used the daily data extracted from the hospital’s information management system for a total of 5944 patients admitted by the outpatient and emergency access during the 2-month periods before and after the release of the open policy in China.Results The findings indicate that the ICU bed optimisation method implemented by the tertiary hospital led to a significant reduction in ALS (HR −0.6764, 95% CI −1.0328 to −0.3201, p=0.000) and ACH (HR −0.2336, 95% CI −0.4741 to −0.0068, p=0.057) among ICU patients after implementation of the open policy. These results were robust across various sensitivity analyses. However, the effect of the optimisation method exhibits heterogeneity among patients admitted through the outpatient and emergency channels.Conclusions This study corroborates a significant positive impact of ICU bed optimisation in mitigating the shortage of medical resources following an epidemic outbreak. The findings hold theoretical and practical implications for identifying effective emergency coordination strategies in managing hospital bed resources during sudden public health emergency events. These insights contribute to the advancement of resource management practices and the promotion of experiences in dealing with public health emergencies.

Drought hardening could promote the development of plant roots, potentially improving the resistance of crops to other adversities. To investigate the response and resistance of physiological and growth characteristics induced by drought hardening to salt stress in the later stages, a greenhouse experiment was carried out from 2021 to 2022 with one blank control treatment and twelve treatments that comprised combinations of four irrigation regimes (W1 = 85%, W2 = 70%, W3 = 55%, and W4 = 40% of the field capacity) and three irrigation water salinity levels (S2, S4, and S6, referring to 2 g, 4 g, and 6 g of sodium chloride added to 1000 mL of tap water, respectively). The results show that saline water irrigation introduced a large amount of salt into the soil, resulting in the deterioration of tomato growth, physiology, yield, and water use efficiency (WUE), but had a positive, significant effect on fruit quality. When the irrigation water salinity was 2 g L−1, the W2 treatment could reduce soil salt accumulation, even at the end of the maturation stage; consequently, enhancing the increments in plant height and leaf area index during the whole growing stage. The physiological activity of tomato plants under the W2 and W3 treatments showed a promoting effect. Correspondingly, the maximum values of the fruit quality of tomato plants irrigated with the same saline water were all obtained with the W2 or W3 treatment. However, the yield and WUE of the W3 treatment were lower than that of the W2 treatment, which was the highest among the same saline water irrigation treatments, consistent with the reflection of the changing trend of the ratio of fresh weight to dry weight. Overall, drought hardening can be considered an economically viable approach to mitigate the hazards of saline water irrigation, and the W2S2 combination is recommended for tomato production due to the maximum values of yield and WUE with a higher fruit quality among the twelve saline water irrigation treatments.

ObjectiveThis study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites.MethodsPatients bitten by a Chinese cobra (Naja atra) (n = 50) that met the inclusion criteria were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group received regular as well as anti-snake venom serum blocking treatment, whereas regular treatment plus chymotrypsin blocking therapy was given to the control group. The necrotic volumes around snake wounds in these groups were detected on the first, third and seventh days. On the third day of treatment, some local tissues in the wounds were randomly selected for pathological biopsy, and the necrosis volume of the local tissue was observed. Furthermore, the amount of time required for wound healing was recorded.ResultsOn the third and seventh days post-treatment, the necrotic volume of the wound of the experimental group was much smaller than that of the control group, and the experimental group's wound healing time was shorter than that of the control group (all p < 0.05). Moreover, the pathological biopsies taken from the control group showed nuclear pyknosis, fragmentation, sparse nuclear density, and blurred edges, and the degree of necrosis was much higher than that of the experimental group.ConclusionsAnti-snake venom blocking therapy is a new and improved therapy with good clinical effect on local tissue necrosis caused by Chinese cobra bites; moreover, it is superior to conventional chymotrypsin blocking therapy in the treatment of cobra bites. It can better neutralize and prevent the spread of the toxin, reduce tissue necrosis, and shorten the course of the disease by promoting healing of the wound. Furthermore, this treatment plan is also applicable to wound necrosis caused by other snake toxins, such as tissue necrosis caused by elapidae and viper families.Clinical trial registrationThis trial is registered in the Chinese Clinical Trial Registry, a primary registry of International Clinical Trial Registry Platform, World Health Organization (Registration No. ChiCTR2200059070; trial URL:http://www.chictr.org.cn/edit.aspx?pid=134353&htm=4).

Background: Stable angina is a common condition with high morbidity and mortality rates. It has been reported that combining oral Chinese patent medicines (OCPMs) and Western medicine (WM) could potentially achieve a better effect than WM alone. However, the optimal OCPMs for stable angina remain controversial and merit further empirical research.Methods: PubMed, Embase, Web of Science, Cochrane Library, Ovid-Medline, Clinical Trials.gov, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database were all searched from inception to 13 March 2022. We employed Version 2 of the Cochrane risk-of-bias tool (ROB2) to assess the overall quality of the selected studies. We also used R 4.1.2 and STATA 14.0 software applications to perform network meta-analysis, followed by sensitivity and subgroup analysis.Results: A total of 179 randomized controlled trials with 16,789 patients were included. The selected trials were all assessed as some concerns. OCPMs combined with WM had a better treatment effect than WM alone. In terms of the effective clinical rate, a significant increase was detected for Qishen Yiqi dripping pill (QSYQ)+WM as compared with Shensong Yangxin capsule (SSYX)+WM, Shexiang Baoxin pill (SXBX)+WM, Tongxinluo capsule (TXL)+WM, Xuefu Zhuyu capsule (XFZY)+WM, Qiliqiangxin capsule (QLQX)+WM, Naoxintong capsule (NXT)+WM, Fufang Danshen dripping pill (FFDS)+WM, and Danlou tablet (DL)+WM. QSYQ + WM had the highest-ranking probability (98.12%). Regarding the effective rate in ECG, QSYQ + WM was superior to SXBX + WM, TXL + WM, DL + WM, FFDS + WM, and NXT + WM. QSYQ + WM ranked first (94.21%). In terms of weekly frequency of angina, QLQX + WM obtained a better effect than FFDS + WM, Kuanxiong aerosol (KXQW)+WM, NXT + WM, QLQX + WM, SSYX + WM, SXBX + WM, and TXL + WM. QLQX + WM ranked first (100.00%). Regarding the duration of an angina attack, KXQW + WM was superior to SSYX + WM; KXQW + WM ranked first (95.71%). Adverting to weekly nitroglycerin usage, TXL + WM had the highest-ranking probability (82.12%). Referring to cardiovascular event rate, DL + WM had the highest effect (73.94%). Additionally, SSYX + WM had the lowest rate of adverse drug reactions (1.14%).Conclusion: OCPMs combined with WM had a higher efficacy. QSYQ + WM, QLQX + WM, KXQW + WM, TXL + WM, DL + WM, SSYX + WM, and SXBX + WM merit further investigation. SXBX + WM is presumably the optimal treatment prescription for both clinically effective and cardiovascular event rates. Further high-quality empirical research is needed to confirm the current results.Systematic Review Registration: URL = https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316534, CRD 42022316534

Background: Acute tonsillitis has high morbidity. Chinese herbal injections (CHIs) were reported to be useful in treating acute tonsillitis and might reduce the probability of antibiotic resistance. Nevertheless, the optimal strategy for combining CHIs with western medicine (WM) to treat acute tonsillitis remains unclear.Methods: We retrieved data from the following databases with retrieval time from inception to 11 January 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. Version 2 of the Cochrane risk-of-bias tool (ROB2) was used for evaluating the quality of the included studies. R 4.1.2, STATA 14.0, and Python 3.10.4 were employed for network meta-analysis, with 5-dimensional K-means cluster analysis, meta-regression analyses, sensitivity analyses, and subgroup analyses.Results: A total of 110 randomized controlled trials including 12,152 patients were included. All the studies were rated as “high risk” and “some concerns”. In terms of improving clinical effectiveness rate, Qingkailing injection + WM ranked ahead of other interventions (89.51%). Regarding reducing antipyretic time, Reduning injection + WM had the highest-ranking probability (68.48%). As for shortening sore throat relief time, Shuanghuanglian injection + WM ranked first (76.82%). Concerning shortening red and swollen tonsils relief time, Yanhuning injection + WM possessed the highest-ranking probability (89.17%). In terms of reducing tonsillar exudate relief time, Xuebijing injection + WM ranked ahead of the other interventions (94.82%). Additionally, the results of the cluster analysis suggested that Xuebijing injection + WM, Reduning injection + WM, and Yanhuning injection + WM were probably the best interventions. Furthermore, adverse drug reactions rate of Xuebijing injection + WM, Reduning injection + WM, Yanhuning injection + WM, Qingkailing injection + WM, and Shuanghuanglian injection + WM were individually 0.00%, 3.11%, 3.08%, 4.29%, and 4.62%.Conclusions: CHIs + WM have a better impact on patients with acute tonsillitis than WM alone. Xuebijing injection, Reduning injection, and Yanhuning injection might have potential advantages in treating the disease. Concerning adverse drug reactions, Xuebijing injection is presumably the optimal CHI. More high-quality studies are needed to further confirm our findings.Systematic Review Registration: CRD42022303243; URL= https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=303243

Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ischemia/reperfusion injury. Wnt signaling is an evolutionarily conserved signaling pathway that has been manifested to play a key role in embryo development and function maintenance in adults. Overactivation of Wnt signaling has previously been investigated in cancer-based research studies. Recently, abnormal Wnt signaling activity has been observed in ischemic stroke, which is accompanied by massive blood–brain barrier (BBB) disruption, neuronal apoptosis, and neuroinflammation within the central nervous system (CNS). Significant therapeutic effects were observed after reactivating the adynamic signaling activity of canonical Wnt signaling in different cell types. To better understand the therapeutic potential of Wnt as a novel target for stroke, we reviewed the role of Wnt signaling in the pathogenesis of stroke in different cell types, including endothelial cells, neurons, oligodendrocytes, and microglia. A comprehensive understanding of Wnt signaling among different cells may help to evaluate its potential value for the development of novel therapeutic strategies based on Wnt activation that can ameliorate complications and improve functional rehabilitation after ischemic stroke.

A novel and atom-economical synthesis of fully substituted 4-aminoimidazoles via gold-catalyzed selective [3 + 2] annulation of 1,2,4-oxadiazoles with ynamides is reported. This protocol represents a new strategy to access α-imino gold carbenes, which corresponds to an unprecedented intermolecular transfer of N-acylimino nitrenes to ynamides. Moreover, the reaction proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale. [ABSTRACT FROM AUTHOR]

A new, versatile, and highly efficient nickel-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a wide variety of arylboronic acids has been developed, yielding cis-2-aryl-1,2-dihydronaphthalen-1-ols in high yields (up to 99%) with good to excellent enantioselectivities (up to 99% ee) under very mild conditions. The effects of various nickel precursors, chiral bidentate ligands, catalyst loadings, bases, solvents, and temperatures on the yield and enantioselectivity of the reaction were also investigated. A plausible mechanism was proposed to account for the formation of the corresponding cis-ring-opened products based on the X-ray structure of product 4b. [ABSTRACT FROM AUTHOR]