ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing， investigate there biological characteristics， and screen effective fungicides， so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges， white， short， velvety aerial hyphae， and pale purple undersides. Macroconidia were colorless， sickle-shaped， with 3-5 septa， while microconidia were transparent， elliptical， aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support， which， combined with morphological characteristics， identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar （MBA） with glucose as the carbon source， beef extract and yeast powder as nitrogen sources， 28 ℃， pH 7.0， and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar （PDA） with glucose as the carbon source， beef extract as the nitrogen source， 28 ℃， pH 7.0， and complete darkness. Among chemical fungicides， phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

Microplastics and nanoplastics (MPs/NPs) are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals (EDCs), raising significant concerns about their impact on human health. Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems, influencing germ cells, embryo development, and progeny. Additionally, studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo, inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation. Considering these adverse effects, identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important. Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects. Among these, anthocyanins, natural colorants responsible for the vibrant hues of fruits and flowers, exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, and anti-neoplastic properties. Moreover, anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity. Cyanidin-3-glucoside (C3G), one of the most extensively studied anthocyanins, shows promise in reducing reproductive toxicity, particularly in females, and in protecting male reproductive organs, including the testis and epididymis. This protective effect is believed to result from its interaction with steroid receptors, specifically the androgen and estrogen receptors (ERs). These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs. This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health, especially concerning reproductive health.

The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 over-expression or activation is sufficient to induce tumor initiation,recurrence,and therapeutic resistance.However,CDK12 may also exert tumor-suppressive functions in a context-dependent manner.Therefore,caution is warranted when targeting CDK12 in future clinical trials.A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance pre-cision oncology.This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer.Subsequently,we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts.Finally,we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology,offering insights into future directions for innovative cancer treatment strategies.

Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health,Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems,influencing germ cells,embryo development,and progeny.Additionally,studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo,inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation,Considering these adverse effects,identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important.Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects.Among these,anthocyanins,natural colorants responsible for the vibrant hues of fruits and flowers,exhibit a wide range of biological activities,including antioxidant,anti-inflammatory,and anti-neoplastic properties.Moreover,anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity.Cyanidin-3-glucoside(C3G),one of the most extensively studied anthocyanins,shows promise in reducing reproductive toxicity,particularly in females,and in protecting male reproductive organs,including the testis and epididymis.This protective effect is believed to result from its interaction with steroid receptors,specifically the androgen and estrogen receptors(ERs).These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs.This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health,especially concerning reproductive health.

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Recommendation formation is a key component of clinical practice guidelines for Chinese patent medicine （CPM）， and should encompass the determination of the strength and direction of the recommendation， the rationale for the recommendation， and the methodology for implementing the recommendation. Recommendations can be formed through formal consensus and informal consensus. The strength and direction of recommendations for CPM guidelines should be determined by considering the quality of evidence for CPMs， the priority of the clinical questions， the pros and cons of efficacy and adverse effects， patient acceptance， the feasibility of the recommendation and the availability of resources， social fairness， economic benefits， and other influencing factors. In order to better guide guideline developers to consider these factors more rationally， this article provideed a detailed explanation of each factor in the context of the characteristics of TCM.