OBJECTIVE: To observe the distribution characteristics of sensitization areas on the body surface in the rat models with functional constipation and diarrhea, explore the regulatory patterns of electroacupuncture (EA) of different intensities at "Tianshu" (ST25) on distal colon motility, and clarify the roles of the neurons of different subtypes in the enteric nervous system (ENS) displayed in the regulatory effect. METHODS: Of 90 SD male rats of SPF grade, 15 rats were randomized into a normal group, a constipation group and a diarrhea group, 5 rats in each one. The stool form and fecal water content, as well as the distribution of the Evans blue (EB) extravasation on the body surface after the intravenous injection with EB on the tails were observed. Eighteen rats were randomized into a normal +2 mA group, a normal +4 mA group and a normal + 6 mA group, 6 rats in each one. Using physiological signal acquisition system, the area under the curve and the average amplitude of colon peristalsis were recorded and analyzed, and the immediate effect on distal colon peristalsis observed after EA with different intensities at "Tianshu" (ST25). Thirty rats were randomized into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea +6 mA group, 6 rats in each one, so as to observe the cumulative effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Twelve rats were randomized into a constipation +2 mA group and a diarrhea +6 mA group, 6 rats in each one, to observe the immediate effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Fifteen rats were randomly divided into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea + 6 mA group, 3 rats in each one. Using the whole-mount staining technique, the expression of vesicular acetylcholine transporter (VAChT)-positive neurons and nitric oxide synthase (nNOS)-positive neurons in ENS was detected. According to the group divisions, the functional constipation models were established by intragastric administration of loperamide hydrochloride (10 mg/kg, once daily, for consecutive 7 days), and the functional diarrhea models were prepared by intragastric administration of folium sennae decoction (10 mL/kg, once daily, for consecutive 2 days). The interventions were delivered with EA of different intensities (the electric current of 2, 4 or 6 mA) at bilateral "Tianshu" (ST25), separately, with the continuous wave and the frequency of 10 Hz used. RESULTS: Compared with the normal group, the fecal amount was decreased, and the fecal water content was reduced in the rats of the constipation group (P<0.001); and loose stool was presented and the fecal water content increased in rats of the diarrhea group (P<0.001). EB extravasation on the body surface happened in the region from T₆ to S₂ of the rats in the constipation and diarrhea groups, and it was more concentrated in the lower abdominal and the lower back regions from T₁₀ to L₃. Compared with the indexes before EA, in the normal +2 mA group and the normal +4 mA group, the areas under the curve and the average amplitude of the distal colon peristalsis were higher during EA delivery (P<0.01, P<0.05), showing a stimulatory immediate effect; and the post-effect was obtained after EA at 2 mA. Whereas, these two indexes were declined during EA in the rats of the normal +6 mA group (P<0.001), showing an inhibitory immediate effect. After many interventions with EA, when compared with those before EA, the above two indexes rose in the constipation +2 mA group (P<0.05, P<0.01), and they were dropped in the diarrhea +6 mA group (P<0.01, P<0.05). The area under the curve of the colon peristalsis in the constipation +2 mA group was higher than that of the constipation group (P<0.001), and that in the diarrhea +6 mA group was lower compared with that in the diarrhea group (P<0.001). The stimulatory effect of EA on colon motility in the constipation +2 mA group was stronger than that of the normal + 2 mA group (P<0.05), and its inhibitory effect was not different statistically in comparison between the normal +6 mA group and the diarrhea +6 mA group (P>0.05). In ENS of the distal colon, after EA at 2 mA, the proportion of VAChT-positive neurons was higher than that of the activated nNOS-positive neurons (P<0.001); and after EA at 6 mA, the activated nNOS-positive neurons were dominant (P<0.001). CONCLUSION In the functional constipation and diarrhea rat models, the sensitization areas on the body surface are centralized in the lower abdominal and the lower back regions of T₁₀ to L₃. Electroacupuncture at "Tianshu" (ST25) has a bidirectional regulatory effect on distal colon motility, and this effect is coordinated with the intensity of electroacupuncture, and may be mediated by ENS neurons of different subtypes.
Animals ; Electroacupuncture ; Male ; Rats ; Colon/innervation* ; Acupuncture Points ; Rats, Sprague-Dawley ; Constipation/physiopathology* ; Gastrointestinal Motility ; Humans ; Diarrhea/physiopathology*

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.