To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Objective:To discuss the anti-tumor effect of low dose of methotrexate(MTX)combined with sorafenib(SFN)on the human osteosarcoma(OS),and to clarify the possible mechanism.Methods:Four types of human OS cells(143B cells,HOS cells,U2OS cells,and MG63 cells)were cultured in vitro.Western blotting method was used to detect the expression levels of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor 2(VEGFR2)proteins in the above four kinds of cells.The human OS xenograft model was established in the nude mice,and 20 successfully modeled BALB/C nude mice were randomly divided into control group(given 2％dimethyl sulfoxide+98％corn oil),low dose of MTX group(given 2 mng·kg-1 MTX),SFN group(given 15 mng·kg-1 SFN),and combined drug group(given 2 mng·kg-1 MTX+15 mng·kg-1 SFN);there were 5 mice in each group.The tumor volumes of the mice in various groups were detected and tumor growth curves were plotted;HE staining was used to observe the morphology of tumor tissue of the mice in various groups;immunohistochemistry was used to detect the positive expression rates of VEGFR2,proliferation marker Ki-67,and hypoxia-inducible factor-1(HIF-1)proteins in tumor tissue of the mice in various groups.The human OS 143B cells were divided into 0,0.125,0.250,0.500,1.000,2.000,and 4.000 μmol·L-1 MTX groups(given 0,0.125,0.250,0.500,1.000,2.000,and 4.000 μmol·L-1 MTX,respectively).CCK-8 method was used to detect the proliferation rates of the 143B cells in various groups,and half inhibityory concentration(IC50)was calculated;the concentration of MTX that had no effect on 143B cell survival was selected as low dose of MTX.The human OS 143B cells were divided into control and low dose of MTX groups(given 0 and 0.250 μmol·L-1 MTX).ELISA method was used to detect the levels of VEGF in the 143B cells in various groups.Results:Compared with 143B cells,the expression levels of VEGF and VEGFR2 proteins in the HOS cells,U2OS cells,and MG63 cells were significantly increased(P＜0.001).In the xenograft model,compared with control group,the tumor volumes of the mice in SFN group,and combined drug group were decreased(P＜0.001);compared with low dose of MTX group and SFN group,the tumor volume of the mice in combined drug group was decreased(P＜0.01).The immunohistochemical results showed that compared with control group,the positive expression rates of Ki-67,VEGFR2,and HIF-1 proteins in tumor tissue of the mice in combined drug group were significantly decreased(P＜0.05).The CCK-8 results showed that there was no change in the proliferation of the 143B cells treated with 0.25 μmol·L-1 MTX.The ELISA results showed that compared with control group,the level of VEGF in the 143B cells in MTX group was signyicantly decreased(P＜0.05).Conclusion:Low dose of MTX enhances the anti-tumor effect of SFN on the human OS,which may be due to the inhibition of VEGF secretion by the OS cells,thereby enhancing the anti-tumor effect of SFN on the human OS.

Objective To investigate the occurrence risk for common complications of internal jugular vein(IJV)and subclavian vein(SCV)catheterization,and provide reference for the prevention and treatment of common com-plications during clinical intravenous infusion therapy.Methods Data from China National Knowledge Infrastruc-ture(CNKI),Wanfang Database,VIP Database,Embase(via OVID),PubMed,Cochrane Library,CINAHL,Web of Science,and ScienceDirect were retrieved,with the search period from database establishment to August 3,2023.Prospective cohort and experimental studies on common complications in patients with IJV and SCV cathete-rization were collected.Meta-analysis on the extracted data was performed with RevMan 5.3 software.Results A total of 29 studies involving 14 096 patients were included in the analysis,including 6 355 patients with SCV cathe-terization(SCV group)and 7 741 patients with IJV catheterization(IJV group).Meta-analysis results showed that the occurrence risk for hemopneumothorax(OR=0.23,95％CI[0.14-0.37])and catheter tip ectopic(OR=0.16,95％CI[0.03-0.85])in SCV group was higher than that in IJV group,and the occurrence risk for central venous catheter-related deep venous thrombosis in IJV group was higher than that in SCV group(OR=2.35,95％CI[1.31-4.21]),with statistically significant differences(all P＜0.01).There were no statistical differences in the occurrence risk of vascular catheter-related bloodstream infection(CRBSI),catheter blockage,and catheter local he-matoma between the two groups(all P＞0.05),there was difference in the combined result of subgroup analysis re-garding catheter bacterial colonization.Conclusion Compared with IJV,patients in SCV group have a higher risk of developing hemopneumothorax and catheter tip ectopic,while patients with catheterization in IJV group have a high-er risk of deep veinous thrombosis.There are no significant differences in the occurrence risk for CRBSI,catheter blockage,and catheter local hematoma between two groups of patients.It is suggested that patient's own conditions and the accessibility of deep vein catheterization should be considered more when selecting the site of deep venous catheterization.

Hemolymphangioma is an extremely rare lymphatic and vascular malformation, recognized as a benign lesion notable for its prolonged clinical course. The digestive tract mainly occurs in the esophagus and colorectum, the small intestine is rarely reported. Here, we report a case of small intestinal hemangiolymphangioma primarily manifesting as gastrointestinal bleeding, with the aim of providing a reference for clinical diagnosis and treatment.

Objective:To evaluate the role of cannabinoid receptor 1 (CB1) in the spinal membrane in electroacupuncture (EA)-induced alleviation of morphine-triggered opioid-induced hyperalgesia (OIH) and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups ( n=12 each) using a random number table method: normal saline group (NS group), morphine group (M group), morphine+ EA group (ME group), and morphine+ EA+ CB1 antagonist group (MEA group). The OIH model was established by intrathecal injection of morphine 15 μg (10 μl) twice a day for 7 consecutive days. The equal volume of normal saline 10 μl was given instead in NS group. EA of the " Yanglingquan" (GB34) and " Zusanli" (ST36) acupoints lasting 30 min was performed after the first administration of medication each day, with a current intensity of 2 mA and frequency of 2 Hz in ME group. In MEA group, morphine (15 μg) and CB1 antagonist AM251 30 μg (10 μl) were intrathecally injected twice a day for 7 consecutive days, with other treatments similar to those previously described in ME group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before administration (T 0) and on days 1, 3, 5 and 7 after administration (T 1-4). Rats were deeply anesthetized and sacrificed at T 3, 4 after administration, and the L 4-6 spinal cord tissues were collected for determination of the expression of membrane CB1, ERK1/2 and p-ERK1/2 by Western blot. Results:Compared with NS group, the MWT was significantly decreased and the TWL was shortened at T 3, 4 in M, ME and MEA groups, the expression of spinal membrane CB1 and p-ERK1/2 was significantly up-regulated at T 4 after administration in M group, and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with M group, the MWT was significantly increased and the TWL was prolonged at T 3, 4, and the expression of p-ERK1/2 was down-regulated at T 4 after administration in ME group ( P<0.05), no significant change was found in MWT or TWL at T 3, 4 in MEA group ( P>0.05), and the expression of spinal membrane CB1 was significantly up-regulated at T 3, 4 after administration in ME and MEA groups ( P<0.05). Compared with ME group, the MWT was significantly decreased and the TWL was shortened at T 3, 4, and the expression of spinal membrane CB1 and p-ERK1/2 was up-regulated at T 4 after administration in MEA group ( P<0.05). Conclusions:Up-regulation of spinal membrane CB1 expression is involved in EA-mediated alleviation of morphine-induced OIH, which is associated with the inhibition of ERK1/2 phosphorylation in rats.