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.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.

Objective To observe the clinical effect and safety of camrelizumab combined with albumin-bound paclitaxel and cisplatin in preoperative neoadjuvant chemotherapy for patients with stage Ⅲa non-small cell lung cancer(NSCLC).Methods Patients with stage Ⅲ a NSCLC were divided into the treatment group and the control group.The control group was treated with intravenous infusion of 130 mg·m-2 of paclitaxel injection on day 1 and day 8,and intravenous infusion of 75 mg·m-2 of cisplatin injection on day 1.In addition to the treatment of control group,the treatment group was treated with intravenous infusion of 200 mg of camrelizumab injection on day 1.Both groups were given 2 cycles of treatment.Clinical efficacy,tumor markers,tumor metastasis markers,T lymphocyte subsets,and safety were compared between the two groups.Results After treatment,the objective remission rate(ORR)of the treatment group and the control group was 69.64％(39 cases/56 cases)and 38.98％(23 cases/59 cases),respectively;the disease control rate(DCR)was 89.29％(50 cases/56 cases)and 72.88％(43 cases/59 cases),respectively;cytokeratin-19-fragment(Cyfra21-1)levels were(3.47±0.86)and(4.01±1.24)ng·mL-1;carcinoembryonic antigen(CEA)levels were(4.55±0.93)and(5.26±1.04)ng·mL-1;neuron-specific enolase(NSE)levels were(16.38±2.51)and(19.02±2.95)ng·mL-1;basic fibroblast growth factor(bFGF)levels were(15.82±2.34)and(18.64±2.59)μg·L-1;carbohydrate antigen 15-3(CA15-3)levels were(22.54±3.10)and(29.41±3.82)ng·mL-1;CD4+/CD8+were 1.42±0.51 and 1.30±0.32.The above indexes were significantly different between the control group and the treatment group(all P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly neutropenia,thrombocytopenia,alopecia,gastrointestinal reaction and radiation pneumonia.There were no significant difference in the incidence of adverse drug reactions between the two groups(all P＞0.05).Conclusion Camrelizumab combined with albumin-bound paclitaxel and cisplatin is effective in the treatment of patients with stage Ⅲa NSCLC.

Objective To explore the distribution patterns of tongue and pulse manifestations and traditional Chinese medicine(TCM)syndrome elements in ischemic stroke(IS)patients of different genders and ages,thus to provide approaches for the prevention and treatment of stroke with TCM.Methods The criteria of six syndrome elements in Diagnostic Scale of Syndrome Elements in Ischemic Stroke were used for the comprehensive identification of syndrome elements in 5 254 cases of inpatients confirmed as IS at the first visit in Shenzhen Traditional Chinese Medicine Hospital from 2017 to 2023.Moreover,the tongue proper,tongue coating,and whose pulse manifestations ranking in the top five in terms of the frequency of occurrence were collected for comparison and analysis.Results(1)For the distribution of TCM syndrome elements in 5 254 cases of IS patients,phlegm-dampness syndrome was the most common syndrome type(3 544 cases,67.5%),and then came qi deficiency syndrome(653 cases,12.4%)and yin deficiency syndrome(453 cases,8.6%).There were statistically significant differences in the distribution of phlegm-dampness syndrome,internal heat syndrome,and yin deficiency syndrome between the male and the female(P＜0.01).And the distribution of phlegm-dampness syndrome,qi deficiency syndrome,internal wind syndrome,and internal heat syndrome in the youth differed from that in the middle-aged and elderly(P＜0.01).(2)The tongue and pulse manifestations in IS patients with the leading six detection rates which ranked in descending order of frequency of occurrence were as follows:dull tongue(1 993 cases,37.9%),dark red tongue(1 907 cases,36.3%),thin and white coating(1 885 cases,35.9%),wiry and slippery pulse(1 714 cases,32.6%),white and greasy coating(1 679 cases,32.0%),and wiry and thready pulse(1 609 cases,30.6%).The detection rates of tongue and pulse manifestations such as light red tongue,thin and white coating in the youth group were significantly higher than those in the middle-aged and elderly group,and the detection rates of dark red tongue,and tooth-marked tongue in the middle-aged and elderly group were significantly higher than those in the youth group,the differences all being statistically significant(P＜0.05).The female patients had higher detection rates of dull tongue,thin and white coating,thin and yellow coating,wiry and thready pulse,and deep and thready pulse than male patients,while the male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,yellow and thick-greasy coating,white and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the females,and the differences were all statistically significant(P＜0.05 or P＜0.01).Higher detection rate of thin and white coating was shown in the youth female than that in the youth male,while higher detection rate of wiry and slippery pulse was shown in the youth male than that in the youth female,and the differences were all statistically significant(P＜0.05 or P＜0.01).The middle-aged and elderly female patients had higher detection rates of dull tongue,thin and white coating,wiry and thready pulse,and deep and thready pulse than the middle-aged and elderly male patients,while the middle-aged and elderly male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,white and thick-greasy coating,yellow and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the middle-aged and elderly female patients,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Phlegm-dampness syndrome,qi deficiency syndrome,and yin deficiency syndrome exert a significant effect on IS,and phlegm-dampness syndrome is the most common syndrome type.Factors such as gender and age have influences on the distribution of TCM syndrome in patients with IS.

AIM: To evaluate the application of single-pass four-throw releasable suture drainage tube ligation technique in Ahmed glaucoma valve(AGV)implantation.METHODS: A total of 78 patients(78 eyes)with refractory glaucoma who underwent AGV implantation in the People's Hospital of Leshan from May 2020 to January 2022 were retrospectively analyzed. According to the treatment, the patients were divided into the modified AGV implantation group, with 43 patients(43 eyes)treated by modified AGV implantation, ligating the drainage tube with single-pass four-throw releasable suture, and the traditional AGV implantation group, with 35 patients(35 eyes)treated by traditional AGV implantation. Followed-up for 6mo, the intraocular pressure(IOP), success rate and complications were observed at 1d, 1 and 2wk and 1 and 6mo after operation.RESULTS: Postoperative IOP at all follow-up visits was significantly lower than that before surgery in both groups(all P<0.05). There was no significant difference in IOP between groups at all follow-up visits(all P>0.05). The incidence of shallow anterior chamber was 5% in the modified AGV implantation group and 23% in the traditional AGV implantation group at 1wk after surgery(P<0.05). At 6mo after operation, the overall success rate was 98% in modified AGV implantation group and 89% in the traditional AGV implantation group(P>0.05).CONCLUSION:During AGV implantation, ligation of drainage tube with single-pass four-throw releasable suture can effectively reduce IOP and reduce the incidence of shallow anterior chamber in early postoperative stage. Furthermore, the technique is safe and efficacious.

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ² test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ²=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ²=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.
Infant ; Female ; Male ; Humans ; Child ; Retrospective Studies ; China/epidemiology* ; Hospitalization ; Community-Acquired Infections/therapy* ; Hospitals, Pediatric ; Pneumonia/therapy*