Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

In the development of traditional Chinese medicine(TCM), the concept of "preventive treatment of disease" has a long history and plays a crucial role in bridging the past and the future. With the continuous growth of public health needs and the ongoing transformation of the registration management of TCM, its position in the research and development of new drugs has become increasingly significant. As one of the important sources of new drug innovation, the new TCM for "preventive treatment of diseases" represents a new thinking proposed based on the current routine registration and research and development. The research and development of TCM for "preventive treatment of diseases" mainly cover four stages: prevention(before the onset of disease), early intervention(when the disease is about to occur), interruption and reversal(when the disease has already occurred), and prevention of recurrence after recovery(after the disease). This study aims to comprehensively analyze the positioning, key points, and difficulties in the research and development of TCM for "preventive treatment of diseases" and explore effective paths to promote the innovative development of TCM through relevant cases. The research and development of new TCM for "preventive treatment of disease" require researchers to seize the opportunities for innovation before the start of the research and development, accurately grasp the key issues at different stages, and pay attention to the full lifecycle evaluation of the drugs. Meanwhile, in the design of the research plan, the optimal effectiveness evaluation indicators should be explored; key and difficult areas such as chronic diseases and rare diseases should be taken seriously, and the limitations of new drug development only based on the diagnosed diseases should be broken, so as to cater to more patients. In addition, through relevant representative cases in China and abroad, the unique advantages of TCM for "preventive treatment of diseases" should be fully leveraged. By learning from the past, all aspects of key points in the evaluation of new drug research and development should be strengthened. Finally, this study proposed that TCM for "preventive treatment of diseases" can employ novel methods and advanced technologies such as new biomarkers and innovative clinical design protocols, as well as new perspectives on disease research and health management. This can provide new paths for the innovation of TCM and public health management.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pharmacy Research

Objective:To prepare mesenchymal stem cells with antioxidant capacity (AO-MSC ) from human umbilical cords and evaluate its cell biological properties.Methods:In control group,mesenchymal stem cells (MSC) were isolated by digesting human umbilical cord Wharton's Jelly tissues with 0.2％ collagenase Ⅱ,and the released cells were collected and cultured in an animal serum-free culture medium.In AO-MSC group,incompletely collagenase Ⅱ-digested tissue debris were allowed to adhere to flusk flat bottoms and the AO-MSC was harvested by adherent culture. The conventional digestion and culture method was used as control.MSC colony forming ability was evaluated by fibroblast colony forming assay (CFU-F).MSC proliferative capacity was evaluated by CCK-8 assay.The MSC surface markers were detected by using flow cytometry and immunofluorescence staining.The adipogenic and osteogenic capacity of MSC was evaluated by multi-differentiation in vitro,and the mRNA expression of genes that control adipogenic and osteogenic differentiation was detected by real-time fluorescence quantitative PCR (RT-qPCR );Moreover,the mRNA expression of antioxidant substances such as SOD-1,GSH,GAT,and NQO1 in MSC was also evaluated by RT-qPCR.Results:The AO-MSC isolated by this strategy reached a confluence of 80％-90％ at around 18 days and grew in a swirling pattern.Flow cytometry and immunofluorescence staining assays showed that CD73,CD29,CD105,CD90 were highly expressed and CD31,CD45,HLA-DR were scarcely expressed in AO-MSC.AO-MSC exhibited stronger self-renewal and differentiation ability compared to MSC.However,the in vitro adipogenic-osteogenic capacity of MSC in the control group was stronger than that of AO-MSC.RT-qPCR assay showed that AO-MSC expressed higher mRNA levels of antioxidant substances compared to MSC.Conclusion:Human AO-MSC is successfully prepared from human umbilical cord without animal serum.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

The rise in global life expectancy has led to an increase in the older population, presenting significant challenges in managing infectious diseases. Aging affects the innate and adaptive immune systems, resulting in chronic low-grade inflammation (inflammaging) and immune function decline (immunosenescence). These changes would impair defense mechanisms, increase susceptibility to infections and reduce vaccine efficacy in older adults. Cellular senescence exacerbates these issues by releasing pro-inflammatory factors, further perpetuating chronic inflammation. Moreover, comorbidities, such as cardiovascular disease and diabetes, which are common in older adults, amplify immune dysfunction, while immunosuppressive medications further complicate responses to infections. This review explores the molecular and cellular mechanisms driving inflammaging and immunosenescence, focusing on genomic instability, telomere attrition, and mitochondrial dysfunction. Additionally, we discussed how aging-associated immune alterations influence responses to bacterial, viral, and parasitic infections and evaluated emerging antiaging strategies, aimed at mitigating these effects to improve health outcomes in the aging population.
Humans ; Aging/physiology* ; Communicable Diseases/immunology* ; Immunosenescence/physiology* ; Inflammation/immunology* ; Genomic Instability

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Humans ; Mice ; Animals ; Caco-2 Cells ; beta Catenin/metabolism* ; Culture Media, Conditioned/pharmacology* ; Tight Junctions/metabolism* ; Intestinal Mucosa ; Inflammatory Bowel Diseases ; Tight Junction Proteins/metabolism* ; Inflammation/metabolism* ; Fibroblasts/metabolism* ; Mice, Inbred C57BL ; Glycoproteins/metabolism* ; Wnt Proteins/pharmacology* ; Frizzled Receptors/metabolism*

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
Child ; Male ; Humans ; Female ; Child, Preschool ; Adolescent ; Crohn Disease ; Inflammatory Bowel Diseases ; Colon ; Inflammation ; Colonoscopy ; Glycoproteins ; Wnt Proteins

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.
Humans ; Sleep Initiation and Maintenance Disorders/therapy* ; Transcranial Magnetic Stimulation ; Brain-Derived Neurotrophic Factor ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; gamma-Aminobutyric Acid ; Depressive Disorder