BACKGROUND: Research has indicated that the disease burden of alopecia areata (AA) in China exceeds the global average. Therefore, accurate and updated epidemiological information is crucial for policymakers. In this study, we aimed to comprehensively assess the disease burden of AA in China. METHODS: The following four key indicators were utilized: the prevalence of cases; disability-adjusted life-years (DALYs); the age-standardized prevalence rate (ASPR); and the age-standardized DALY rate (ASDR) of AA according to the Global Burden of Disease (GBD) study 2021. We analyzed the epidemiological burden of AA in China during 2021, examined changes between 1990 and 2021, and performed a Bayesian age-period-cohort analysis to predict trends over the course of the next decade (2022-2030). Additionally, a Gaussian process regression model was applied to estimate the relationship between the gross domestic product (GDP) and the ASPR and ASDR of AA at the provincial level between 1992 and 2021. RESULTS: In 2021, the estimated number of patients with AA in China was approximately 3.49 million (95% uncertainty interval [UI], 3.37-3.62 million); of these patients, 1.20 million (95% UI, 1.16-1.25 million) were male and 2.29 million (95% UI, 2.20-2.37 million) were female. This large number of patients with AA resulted in a total of 114,431.25 DALYs (95% UI, 74,780.27-160,318.96 DALYs). Additionally, the ASPR and ASDR were 224.61 per 100,000 population (95% UI, 216.73-232.65 per 100,000 population) and 7.41 per 100,000 population (95% UI, 4.85-10.44 per 100,000 population), respectively; both of these rates were higher than the global averages. The most affected demographic groups were young and female individuals 25-39 years of age. Slight regional disparities were observed, with the northern and central regions of China bearing comparatively higher burdens. Between 1990 and 2021, the health loss and disease burden caused by AA in China remained relatively stable. The ASPR and ASDR of AA increased with the GDP when the annual GDP was less than 2 trillion Chinese yuan; however, a downward trend was observed as the GDP surpassed 2 trillion Chinese yuan. A slight upward trend in the disease burden of AA in China is predicted to occur over the next decade. CONCLUSIONS AA continues to be a public health concern in China that shows no signs of declining. Targeted efforts for young individuals and females are necessary because they experience a disproportionately high burden of AA.
Humans ; China/epidemiology* ; Alopecia Areata/epidemiology* ; Global Burden of Disease ; Female ; Male ; Adult ; Disability-Adjusted Life Years ; Middle Aged ; Prevalence ; Adolescent ; Young Adult ; Bayes Theorem ; Child ; Quality-Adjusted Life Years ; Child, Preschool

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*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective To investigate the acute toxicity,irritation,and other effects of Shexiang Anhe hemorrhoid ointment on hemorrhoid-phased model rats by examining the TLR4/p38 MAPK/NF-κB signaling pathway.Methods Sixteen New Zealand rabbits were randomly divided into an intact skin Shexiang Anhe hemorrhoid ointment group,intact skin control group,broken skin Shexiang Anhe hemorrhoid ointment group,and broken skin control group,with four rabbits in each group.In the experimental group,20 g of Shexiang Anhe hemorrhoid ointment(1 g/mL)was evenly applied to an area on the rabbits depleted of hair,and an equal volume of solvent(mixture of glycerol,lanolin,and water)was evenly applied to the area on the backs of the rabbits in the control group once a day for 14 days.Another 40 rats were taken and randomly divided into a normal group,model group,Maillard group,and hemorrhoid cream group,with 10 animals in each group.The cream was applied once a day for 14 days.The acute toxicity of the cream in the intact and broken skin of rabbits was observed by hematoxylin and eosin staining and other method after treatment.In situ photographs were taken of the perianal tissues of rats with hemorrhoids to observe the efficacy of Shexiang Anhe hemorrhoid ointment,and the length and width of the ulcers were measured with vernier calipers to calculate the area.Quantitative real time polymerase chain reaction was used to detect the expression of TLR4,p38 MAPK,and NF-κB mRNA in the perianal tissues of the rats.Results Compared with rabbits in the control groups with intact or broken skin,rabbits in the administered group showed no significant difference in body mass.The mean values for the irritation evaluation points for Shexiang Anhe hemorrhoid ointment on rabbits with broken skin for 1 h,24 h,48 h,and 72 h were 1.5,1,0.5,and 0.25,respectively,showing there was no obvious skin irritation.In the hemorrhoidal rats,Shexiang Anhe hemorrhoid ointment treatment significantly reduced hemorrhoid symptoms after 14 days administration;the ulcer area was significantly smaller(P＜0.05)and TLR4,p38 MAPK,and NF-κB mRNA levels were significantly lower compared with the findings in the model group(P＜0.05).Conclusions Shexiang Anhe hemorrhoid ointment is a safe topical treatment with minimal acute toxicity and irritation to the skin and achieved good efficacy in the treatment of hemorrhoidal rats.Its mechanism of action may be related to the inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway.

Objective:To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model.Methods:A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect.Results:① Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×10 9/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio ( OR) = 3.063, 95% confidence interval (95% CI) was 1.200-7.819], blood purification catheter function ( OR = 4.429, 95% CI was 1.270-15.451), blood flow rate ( OR = 0.928, 95% CI was 0.900-0.957), and frequency of blood pump stops ( OR = 1.339, 95% CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95% CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. ② External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95% CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. Conclusion:The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective To construct an intervention programme for breastfeeding among mothers of infants with congenital heart disease and to verify its effect.Methods Taking the capability-opportunity-motivation-behaviour model as the theoretical basis,the first draft of the intervention programme was formed through literature search and semi-structured interviews,and 8 experts in the relevant fields were selected to conduct expert validation and determine the content of the program.By the consecutive sampling method,infants and their mothers who attended the cardiothoracic disease clinic of a tertiary-level children's specialist hospital in Shanghai from 4 May to 24 June 2023,with a day-old age of≤14 d and a confirmed diagnosis of CHD,were selected as the study subjects.They were divided into an experimental group and a control group,with 16 cases in each group,by the method of randomized grouping by district.The experimental group received breastfeeding intervention for mothers of infants with CHD on the basis of routine care;the control group received routine care and basic disease education and breastfeeding counselling.At 1 and 3 months of the infants with CHD,the 2 groups were compared in terms of exclusive breastfeeding rate,daily human milk as a percentage of total feeds,weight for age Z-score and height for age Z-score.Results A total of 1 round of expert validation was conducted,with a valid questionnaire recovery rate of 100％and an expert authority coefficient of 0.94.The breastfeeding intervention programme for mothers of infants with CHD is a comprehensive approach that encompasses 3 key dimensions,including capability,opportunity,and motivation.The programme is designed to enhance mothers'ability to recognize feeding signals,master breastfeeding techniques,and maintain successful breastfeeding practices.It also addresses common breastfeeding challenges and provides effective solutions.Additionally,it includes strategies for breastmilk management and fosters family support for breastfeeding.The programme offers medical information support on breastfeeding and aims to elevate mothers'understanding of its benefits.It involves systematic monitoring and recording of breastfeeding volumes,as well as thorough assessments and guidance on infant growth and development,including but not limited to the 10 specific entries related to the infant's progress.The results of the generalized estimating equations and repeated measures analysis of variance revealed statistically significant between-group differences(P＜0.05)in the rates of exclusive breastfeeding,the proportion of daily human milk as a percentage of total feeds,and the weight-for-age(WAZ)and height-for-age(HAZ)z-scores of infants across the 2 groups at various time points.The results of simple effect analysis showed that the differences in exclusive breastfeeding rate,the proportion of daily human milk as a percentage of total feeds,WAZ and HAZ between the 2 groups before intervention were not statistically significant(P＞0.05).At the age of 3 months of the infants after the intervention,the rate of exclusive breastfeeding in the experimental group was higher than that in the control group,and the difference was statistically significant(P=0.003).The proportion of daily human milk as a percentage of total feeds for infants in the intervention group at 1 and 3 months of age was higher than that in the control group,with a statistically significant difference(P＜0.05).At 3 months of age,WAZ of the experimental group was higher than that of the control group,and the difference was statistically significant(P=0.037);HAZ of the experimental group was higher than that of the control group at 1 and 3 months of age after intervention,and the difference was statistically significant(P＜0.05).Conclusion The breastfeeding intervention programme for mothers of infants with CHD,constructed on the basis of the COM-B model in this study,was comprehensive,feasible and acceptable.Implementation of the programme has potential positive effects on increasing exclusive breastfeeding rates and the daily human milk as a percentage of total feeds,and may also have a positive impact on WAZ and HAZ of infants.