BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Male ; Rats ; Gastrointestinal Microbiome/genetics* ; Chromatography, High Pressure Liquid ; Humans ; Mass Spectrometry ; RNA, Ribosomal, 16S/genetics* ; Bacteria/drug effects*

Based on the similarity of chemical constituents between Panax notoginseng flowers and rhizomes, this study investigated their lipid-lowering effects and impacts on the intestinal flora of rats. The main components of P. notoginseng flowers and rhizomes were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) to compare their chemical similarities. A hyperlipidemia rat model was induced using a high-fat diet. After successful modeling, the rats were divided into the blank control group, blank administration group(0.090 g·kg~(-1)), model group, low-(0.045 g·kg~(-1)), medium-(0.090 g·kg~(-1)), high-dose(0.180 g·kg~(-1)) P. notoginseng flower group, P. notoginseng rhizome group(0.270 g·kg~(-1)), and simvastatin group(0.900 mg·kg~(-1)). After modeling, the rats were given intragastric administration for 3 weeks, once daily, while their body weight was recorded regularly. Before the last administration, fresh feces were collected for analysis of changes in intestinal flora using 16S rDNA high-throughput sequencing technology. One hour after the last administration, the rats were anesthetized with 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Serum biochemical indexes were detected using an automatic biochemical analyzer. Organs(heart, liver, spleen, lung, and kidney) were harvested, and organ index were calculated. Liver tissue pathology was assessed through HE staining and oil red O staining. The results indicated that there were 33 identical chemical constituents in P. notoginseng flowers and rhizomes, accounting for 75.00% of the total constituents. After treatment, high-dose P. notoginseng flower group and P. notoginseng rhizome group exhibited similar effects on body weight, serum biochemical indexes, and liver histopathological conditions. Compared with model control group, the abundance of Firmicutes and Actinobacteria increased in high-dose P. notoginseng flower and rhizome groups, while the abundance of Bacteroidetes and Thermodesulfobacteria decreased. Cluster analysis showed no significant difference between the two groups. Both P. notoginseng flowers and rhizomes possess similar chemical components and lipid-lowering effects, and they can regulate the intestinal flora imbalance caused by hyperlipidemia, indicating their potential for use in hyperlipidemia treatment.
Animals ; Hyperlipidemias/microbiology* ; Panax notoginseng/chemistry* ; Rats ; Rhizome/chemistry* ; Male ; Flowers/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/administration & dosage* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Liver/drug effects*

This study aims to investigate the scientificity and efficacy of the compatibility of Jinlingzi San from pharmacokinetics. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was utilized to determine the plasma concentrations of the active components: toosendanin, tetrahydropalmatine A, and tetrahydropalmatine B at various time points following the gavage of Jinlingzi San and its single medicines in rats. Subsequently, WinNonlin was employed to calculate pertinent pharmacokinetic parameters. The pharmacokinetic parameters in rat plasma were compared between the single medicines and the compound formula of Jinlingzi San. It was discovered that the area under the curve(AUC_(all)) and peak concentrations(C_(max)) of tetrahydropalmatine A, and tetrahydropalmatine B were significantly elevated in the compound formula group compared with the single medicine groups. Conversely, the AUC_(all )and C_(max) of toosendanin notably decreased. Furthermore, the compound formula group had longer mean residence time(MRT) and lower apparent clearance(CL/F) of all three active ingredients than the single medicine groups(P<0.05). These findings indicated that Jinlingzi San enhanced the absorption of tetrahydropalmatine A and tetrahydropalmatine B in vivo, facilitating their pharmacological actions. Concurrently, it inhibited the absorption of toosendanin, thereby preventing potential toxic reactions. Moreover, the compatibility prolonged the residence time of the active ingredients in the body. This study provides a reference for exploring the compatibility rationality of Jinlingzi San.
Animals ; Rats ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Chromatography, Liquid/methods* ; Berberine Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*