Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally， the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group. MethodsThis study was conducted in the Chongming area of Shanghai， China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index（SMI） was measured by bioelectrical impedance analysis（BIA）， and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis， chi-square test， and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass. ResultsIn terms of food intake categories， compared with the long-lived elderly people with normal muscle mass， the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. In terms of the nutrient intake， compared with the long-lived elderly people with normal muscle mass， the intake of total energy， carbohydrate， dietary fiber， vitamin D， folic acid， phosphorus， potassium， magnesium， iron， and manganese in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. After continuous adjustment for the covariates， multivariate logistic regression analysis found that the intake levels of folic acid and dietary fiber were important factors influencing skeletal muscle mass， Individuals with lower intake levels of folic acid and dietary fiber are at a higher risk of low muscle mass in long-lived elderly individuals ［OR_{folic acid T1}， _{dietary fiber T1} （95%CI）： 2.90 （1.11‒7.61）； 4.09 （1.53‒10.91）］. ConclusionThe consumption of cereals that include a variety of beans and vegetables was noticeably lower in the long-lived elderly individuals with lower muscle mass when compared to those with normal muscle mass. Furthermore， low levels of folic acid and dietary fiber intake are associated with an increased risk of low skeletal muscle mass.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To analyze the epidemic characteristics of brucellosis in China from 2004 to 2018, in order to understand the development trend of brucellosis.Methods:The surveillance data of brucellosis in China from 2004 to 2018 were collected from National Public Health Science Data Center. Joinpoint regression was used to analyze the trend of brucellosis incidence in China and various provinces. Overall trends were estimated by the average annual percentage change (AAPC). Seasonal and trend decomposition using loess (STL) was used to analyze the seasonal characteristics of brucellosis in China and various provinces. The age-related thermodynamic diagram of incidence rate was used to analyze the characteristics of age-onset changes.Results:From 2004 to 2018, a total of 524 980 brucellosis cases and 16 deaths were reported nationwide, with a incidence rate of 2.61/100 000 and a case fatality rate of (3.05 × 10 -3)%. The incidence of brucellosis in China was on the rise (AAPC = 11.58%, 95% CI: 7.91% - 15.25%, P < 0.001). There was no significant trend of change in Inner Mongolia Autonomous Region, Shanxi and Shaanxi provinces ( P > 0.05). Tibet Autonomous Region showed a downward trend (AAPC = - 55.19%, P < 0.001). All other provinces were showing an upward trend (AAPC > 0, P < 0.05). The peak incidence in China occurred from April to June. In terms of provinces, the peak incidence in Hainan, Sichuan, Guizhou, Fujian and Anhui provinces occurred from April to August, the peak incidence in Chongqing and Shanghai cities occurred from June to August, and the peak incidence in other provinces was generally from April to June. There were reports of brucellosis cases in all age groups nationwide, and the age distribution showed an inverted "V" shape. The peak incidence occurred in the 50 - 54 years old (5.43/100 000), followed by the 60 - 64 years old (4.94/100 000). From 2004 to 2018, the top 3 age groups of incidence rate changed from 40 - 44, 50 - 54 and 35 - 39 years old in 2004 to 50 - 54, 60 - 64 and 55 - 59 years old in 2018. Conclusions:The incidence of brucellosis is on the rise nationwide and in most provinces from 2004 to 2018. The high incidence age is gradually changing to the elderly population.

Objective:To explore the effects of online mindfulness-based stress reduction(MBSR)on the anxiety and depression status,and quality of life in the caregivers of patients with severe mental disorders.Methods:Ninety-three caregivers for patients with schizophrenia or bipolar disorder,who were hospitalized in Yunnan Provincial Mental Hospital in March 2021,were enrolled and randomly divided into control group(n=47)and MBSR intervention group(n=46).Both groups received basic health education and rehabilitation skill training,while the intervention group received additional online MBSR for 8 weeks.The anxiety and depression status,and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS)and the 36-item Short Form Health Survey(SF-36)before and 8 weeks after intervention,respectively.Results:Thirteen caregivers dropped out of the study,and 80 subjects(40 in each group)were included in the final analysis.At the baseline,there were no significant differences in SAS,SDS and SF-36 scores between two groups(all P>0.05).Compared with the baseline,SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention(both P<0.01)and were significantly lower than those in the control group(both P<0.01).There were no significant changes in the control group(all P>0.05).Except the physiological function dimension,the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention(all P<0.05),and were significantly higher than those in the control group(all P<0.01).There were no significant changes in the control group before and after intervention(all P>0.05).Conclusion:Online MBSR can reduce the anxiety and depression levels,improve the quality of life in the caregivers of patients with severe mental disorders.

Objective:To learn about the age, period, birth cohort characteristics, and incidence trends of hemorrhagic fever with renal syndrome (HFRS) nationwide.Methods:HFRS monitoring data from 2004 to 2018 were collected from the National Public Health Science Data Center (https://www.phsciencedata.cn/). The trend of incidence rate of HFRS was analyzed by joinpoint regression, and the linear trend was estimated by annual percentage change (APC) and average annual percentage change (AAPC). Bayesian Age-Period-Cohort (BAPC) analysis of the effects of age, period, and birth cohort on HFRS cases was conducted, with age, period, and birth cohort used as reference for the 40 - 44 age group, 2011, and 1968, respectively, the RR and 95% CI were calculated. Results:From 2004 to 2018, a total of 190 197 HFRS cases were reported nationwide, with an average annual incidence rate of 0.95/100 000. Among them, the highest incidence rate of HFRS was 1.93/100 000 in 2004. Since 2007, it had continued to fluctuate below 1.00/100 000, ranging from 0.66/100 000 to 0.99/100 000. Joinpoint regression fitting results showed that the overall incidence of HFRS in China was declining (AAPC = - 7.33%, 95% CI: - 8.07% - - 6.58%, P < 0.001); the APCs from 2004 to 2007, 2007 to 2009, and 2012 to 2016 were - 32.00%, - 8.74%, and - 9.02%, respectively, all showed a downward trend( P < 0.05); the APCs from 2009 to 2012 and from 2016 to 2018 were 14.69% and 11.38%, respectively, both showed an upward trend ( P < 0.05). HFRS cases were reported in all age groups, and the reported incidence rate showed a unimodal distribution with age. Among them, the highest incidence rate was in the 50 - 54 age group (1.75/100 000), and the lowest incidence rate was in the 0 - 4 age group (0.03/100 000); the proportion of cases in the age group of 60 years and above increased from 9.75% in 2004 to 25.90% in 2018, showed an increasing trend year by year (χ 2trend = 9 210.90, P<0.001). The analysis results of the BAPC model showed that in the age effect analysis, compared with the reference age group, there was no significant difference in the incidence risk among the age groups of 15 - 79 years old ( P > 0.05), while the incidence risk was lower in the age groups of 14 years old and below, and 80 years old and above ( RR < 1, P < 0.05). In the analysis of period effects, compared with the reference year, the incidence risk was higher from 2004 to 2006 and from 2012 to 2014 ( RR > 1 , P < 0.05), and lower from 2008 to 2010 and from 2017 to 2018 ( RR < 1, P < 0.05); the overall trend was consistent with the descriptive analysis of onset period. In the analysis of birth cohort effect, compared with the reference cohort, the population born between 1920 - 1935 and 1970 - 2018 had lower incidence risk ( RR < 1, P < 0.05); but the risk of disease in the population born after 2003 showed an upward trend. Conclusions:The HFRS epidemic in China has decreased from 2004 to 2018, but the downward trend in recent years is not significant. The incidence risk has increased among people born after 2003. The population aged 60 and above is a key group for further controlling the HFRS epidemic in China.