The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

By reviewing the physical biological research on the activation of acupoint effects by acupuncture， this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture， and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells， further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints， and the physical-chemical information transduction mechanism， which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

Objective To investigate the effects of varying durations of overwork on cardiomyocyte pyroptosis in mice.Methods A total of 24 SPF KM mice were randomly divided into four groups(n=6)using a random number table:control group,2-week overwork(W2)group,4-week overwork(W4)group,and 6-week overwork(W6)group.Mice in control group were normally raised,while those in W2,W4,and W6 groups were forced to stand in water for 8 h and then restrained for 3 h daily for 2,4,6 weeks,respectively.The general condition and weekly weight changes of the mice were observed.After modeling,blood samples were collected,and hearts were excised.Myocardial histopathological changes were assessed using hematoxylin and eosin(HE)staining.The localization of gasdermin D(GSDMD)protein in myocardial tissue was detected through immunohistochemical staining,and the expression levels of pyroptosis-related proteins[NOD-like protein receptor 3(NLRP3),Caspase-1,GSDMD]in myocardial tissue were analyzed using Western blotting.The contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in serum and myocardial tissues were measured using ELISA.Results(1)The weight of control group mice increased steadily within 2 weeks.In W2 group,there was no significant weight change within 2 weeks,while in W4 and W6 groups,the body weights were higher than their initial values from the 2nd to 6th week.Compared with control group,the body weights of W2,W4,and W6 groups were lower than those of control group in the 1st and 2nd week,with statistically significant differences(P<0.05).The activity levels of the mice in W2,W4,and W6 groups initially increased and then decreased,with their fur becoming dull and falling out,and their mental state deteriorating.(2)In control group,cardiomyocytes were neatly arranged,and the nuclear morphology was normal.Compared with control group,in W2 group,cardiomyocyte arrangement was less regular,and capillary congestion was increased.In W4 group,the vascular congestion in the myocardium was significantly increased,the interstitial tissue was hyperplastic,and vacuolization appeared around the nuclei.In W6 group,the myocardial interstitium was loose,fat infiltration was increased,vacuolization around the nuclei was increased,and myocardial fibers were swollen,and the arrangement was disordered.(3)GSDMD was mainly located in the cytoplasm of cardiomyocytes.Compared with control group,the expression levels of NLRP3,Caspase-1,and GSDMD proteins in W2,W4,and W6 groups were significantly increased,and the expression levels were in the order of W6 group>W4 group>W2 group,with significant differences(P<0.05).(4)Compared to control group,the levels of IL-1β in serum and myocardial tissues of W2,W4,and W6 groups were significantly increased.In serum,the level of IL-1β in W6 group was higher than those in W2 and W4 groups,and in myocardial tissue,the levels in W4 and W6 groups were higher than those in the W2 group,with significant differences(P<0.05).There were no significant differences in IL-1β levels in serum among W2 and W4 groups,nor were there significant differences in myocardial tissue between W4 and W6 groups(P>0.05).Compared with control group,the levels of IL-18 in serum and myocardial tissue of W4 and W6 groups were significantly increased(P<0.05).In serum,the levels of IL-18 in W4 and W6 groups were higher than that in W2 group,and in myocardial tissue,the level in W6 group was higher than those in W2 and W4 groups,with the differences being statistically significant(P<0.05).Conclusions Overwork can cause structural damage to mouse myocardial tissue,increase the expression of pyroptosis proteins NLRP3,Caspase-1,GSDMD,and aggravate myocardial inflammatory responses in overworked mice.Cardiomyocyte pyroptosis may be one of the factors contributing to sudden cardiac death induced by overwork.

Objective:To apply statistical process control (SPC) techniques to the quality assurance of non-normal radiotherapy plans through Johnson transformation, establishing patient-specific tolerance and action limits based on treatment sites and dose/distance assessment criteria, thereby enhancing the intensity-modulated radiation therapy (IMRT) verification accuracy and dose delivery precision.Methods:In this study, 951 gamma analysis data of patient-specific quality assurance (PSQA) executed on the Halcyon accelerator platform were selected and categorized into six groups based on treatment sites, including brain (102 cases), head and neck (100 cases), breast (229 cases), lung (154 cases), esophagus (223 cases), and pelvic (143 cases) groups. The six groups of data were statistically analyzed through Anderson-Darling normality tests ( α = 0.05) using Minitab 21 software. Non-normal data were transformed into normal data through Johnson transformation and then were used to establish treatment site-specific tolerance and action limits, which were compared with the Shewhart control charts based on normal distributions. Results:The PSQA result of the six groups all exhibited non-normal distributions ( P < 0.05). Through Johnson transformation, the tolerance and action limits for the head and neck, breast, lung, esophagus, and pelvic areas under the 3%/2 mm criterion ranged from 95.13% to 96.16% and 94.19% to 95.91%, respectively. In contrast, the tolerance and action limits ranged from 91.15% to 94.86% and 89.94% to 94.78% under the 2%/2 mm criterion. Directly applying Shewhart control charts without normality assumptions yielded higher tolerance limits compared to the application of Johnson transformation, increasing the false positive rate in the non-normal PSQA process. Conclusions:Applying the SPC techniques directly to a non-normal process can lead to an increased false alarm rate and wrong process interpretation. The SPC techniques combined with Johnson transformation enable more effective monitoring of a non-normal PSQA process, facilitating timely identification of potential factors that may lead to an out-of-control process based on the treatment site-specific limits.

OBJECTIVE To observe the effects of measures dominated by intensifying link quality on prevention and control of carbapenem-resistant Klebsiella pneumoniae(CRKP)among general ICU patients.METHODS The conventional intervention measures were taken from Jan.2016 to Oct.2020,which was assigned as the pre-inter-vention period;the intervention measures dominated by enhancement of link quality were taken for the general ICU patients(the study group)from Nov.2020 to Oct.2021,which was set as the intervention period,the inter-vention measures were taken for the neurosurgery ICU patients and the surgery ICU patients(the control group).A two-group interrupted time series of a quasi-experimental study was analyzed,and whether or not the intervention measures could reduce the incidence of CRKP hospital-associated infection among the general ICU patients was evaluated.RESULTS A total of 23 713 case-times of patients from three ICU wards were enrolled in the study.The incidence of CRKP hospital-associated infection among the general ICU patients was 4.49 cases per thousand patient-days during intervention period,3.71 cases per thousand patient-days during pre-intervention pe-riod,and there was no significant difference(u=-1.412,P=0.079);it was lower than 7.06 cases per thousand patient-days during nearly one year before the intervention period(from Nov.2019 to Oct.2020),and there was significant difference(u=3.128,P=0.002).The result of analysis of the interrupted time series showed that there was significant difference in the slope change between the study group and the control group after the inter-vention(P=0.035),indicating that the intervention measures could reduce the incidence of CRKP hospital-associ-ated infection in the study group,and there was significant difference in the changing trend between the study group and the control group.CONCLUSIONS The prevention and control measures for CRKP dominated by the link quality management can effectively reduce the incidence of CRKP hospital-associated infection among the gen-eral ICU patients.The prevention and control strategies may provide reference for prevention and control of CRKP in ICUs of other medical institutions.

Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.