Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.

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.

Slag is a typical metallurgical solid waste,mainly composed of magnesium oxide,iron oxide,alumina oxide and other metal oxides.The rapid quantitative analysis of slag components is helpful to determine the content of valuable elements or components in slag,and then choose a suitable resource utilization way to achieve efficient utilization and reduce environmental pollution.In this study,a quantitative analysis method of Fe,Si and Ti in slag was proposed based on laser induced breakdown spectroscopy(LIBS)combined with machine learning algorithm.Firstly,LIBS spectra of slag samples were collected,and the characteristic spectral lines of related elements were identified through the National Institute of Standards and Technology(NIST)database.Then,the influence of different spectral preprocessing methods on the predictive performance of PLS model was investigated,and the combined performance of spectral preprocessing methods was discussed.On this basis,a mixed variable selection algorithm combining variable importance in projection(VIP)and grey wolf algorithm(GWO)was proposed to screen LIBS spectral characteristic variables of slag samples.Based on cross-validation,the parameters,thresholds,input variables and model parameters of the preprocessing method and feature screening method were optimized.A quantitative analysis model of Fe,Si and Ti in slag based on LIBS technique was established based on the optimized parameters and input variables.The results showed that the optimized model had better prediction performance than the original spectral model,with R2p of 0.9525,0.9604 and 0.9972,and RMSEp of 0.0461,0.0141 and 0.1963,respectively.It was proved that LIBS combined with machine learning algorithm provided a feasible method for the field rapid detection of slag elements.The research is expected to provide some theoretical basis and technical reference for the resource utilization of metallurgical solid waste.

Objective:To investigate the demand and influencing factors of home care social support services for the elderly with dementia in urban areas, and provide a decision-making basis for improving home care social support services for the elderly with dementia.Methods:This was a cross-sectional study. From March 2021 to March 2022, 386 family caregivers of elderly people with dementia were randomly selected from tertiary hospitals in four central urban areas of Wuhan by stratified sampling method. A questionnaire was used to investigate the current situation and attributes of the demand for home care social support services for the elderly with dementia in urban areas. The importance of the demand for home care social support services for the elderly with dementia in urban areas was calculated by the Better-Worse coefficient method and sensitivity formula method. The optimal scale regression model was used to analyze the influencing factors and influencing forces of independent variables on service demand.Results:The score of social support service demand for home care was (88.6 ± 29.71) points. The Better coefficient of demand for all social support services was greater than the absolute value of the Worse coefficient. One requirement (pressure ulcer prevention and treatment guidance) was a one-dimensional attribute, and the remaining 29 items were charm attributes. The top 6 items in importance ranking were 2 items of informational support (pressure ulcer prevention and treatment guidance; telephone counselling guidance for family caregivers), 1 items of instrumental support (financial assistance for family caregivers) and 3 items of social companionship support(cultural recreation/physical activity activities, door-to-door accompaniment, accompany the elderly to social activities). Optimal scale regression model test: all four models of social support service demand were statistically significant ( F values were 2.75-4.23, all P <0.01). The gender, education level, number of children of the elderly with dementia, age,education level, self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and the elderly with dementia were the influencing factors of self-esteem support (all P<0.05). The educational level, marital status, type of dementia of the elderly with dementia, educational level, self rated physical condition of family caregivers, the average monthly income of the family, and the relationship between family caregivers and the elderly with dementia were the influencing factors of informational support (all P <0.05). The educational level and type of dementia of the elderly with dementia, the educational level, self rated physical condition of family caregivers, and the average monthly income of families were the influencing factors of social companionship support (all P <0.05). The type of dementia of the elderly with dementia, the self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and elderly relatives were the influencing factors of instrumental support (all P <0.05). Five times for caregiver human resources, 3 times for family economic resources and 3 times for the elderly with dementia, and 1 time for relatives resource factors were the top 3 times of independent variable influence force entered the ranking. Conclusions:The demand for social support services for home care of the elderly with dementia is low, with the characteristics of expectant tendency and centralized demand. The provision of home-based care social support services should give priority to meeting the needs of "pressure ulcer prevention and treatment guidance", and provide financial assistance, counseling and guidance, social companionship and other services as much as possible. Caregiver human resources are the key factors affecting home care social support services, family economic resources and the elderly with dementia are important factors, it is recommended to fully tap the potential of relatives resources and community resources.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

AIM: To summarize the clinical features of the 24h intraocular pressure data and the water drinking test(WDT)results in patients with primary open angle glaucoma(POAG)and ocular hypertension(OHT), and analyze the correlation.METHODS: To collect the data of 87 cases(174 eyes)with POAG and OHT, who had completed 24h intraocular pressure(IOP)(measured every 2h)and WDT(drink 1 000mL water off within 5min and then measure every 15min within 1h)in the ophthalmology department of Shenzhen University General Hospital from December 2019 to March 2022. They were divided into three groups, with 33 cases(66 eyes)in high tension glaucoma(HTG)group, 28 cases(56 eyes)in normal tension glaucoma(NTG)group and 26 cases(52 eyes)in OHT group. The clinical features of 24h IOP and WDT among the patients in three groups were summarized, and Spearman correlation was used to analyze the peak and fluctuation values of IOP.RESULTS: Clinical features among the patients in three groups:(1)the proportion of peak IOP of HTG, NTG and OHT group:(2:00-6:00 a.m.): 40.9%, 23.2% and 26.9%;(8:00-12:00 a.m.): 34.8%, 46.4% and 55.8%;(14:00-18:00 p.m.): 18.2%, 21.4% and 11.5%;(20:00-24:00 p.m.): 6.1%, 8.9% and 5.8%. Valley proportion among groups: early morning: 21.2%, 25.0% and 30.8%; morning: 22.7%, 10.7% and 13.5%; afternoon: 19.7%, 17.9% and 17.3%; evening: 36.4%, 46.4% and 38.5%. The proportion of 24h IOP fluctuation <6mmHg: 9.1%, 62.5% and 17.3%; 6-<8mmHg: 24.2%, 32.1% and 40.4%; ≥8mmHg: 66.7%, 5.4% and 42.3%.(2)WDT: The proportion of the three groups that could reach peak IOP within 30min was 81.8%, 76.8% and 80.8%, respectively. The proportion of IOP fluctuations in the three groups <6mmHg: 10.6%, 78.6% and 38.5%; 6-<8mmHg: 22.7%, 16.1% and 28.8%; ≥8mmHg: 66.7%, 5.4% and 32.7%.(3)the proportions of WDT peak higher than 24h peak IOP in the three groups were 80.3%, 80.4% and 80.8%. Correlation: the peak values of 24h IOP were positively correlated with the peak values of WDT(all P<0.01), the fluctuation of 24h IOP was positively correlated with the fluctuation of WDT in HTG and OHT group(P<0.01, P<0.05), while it showed no significant correlation in NTG group(P>0.05).CONCLUSION: Diurnal measurements of IOP during office hours(08:00 a.m.-18:00 p.m.)may fail to capture the peak values and underestimate IOP fluctuations. The 24h IOP fluctuation ≥HTG group of 8mmHg>OHT group>NTG group. The peak WDT in over 75% patients could be achieved within 30min, and it was higher than 24h peak IOP of over 80% patients. There was a positive correlation between the 24h IOP fluctuations and the WDT fluctuations in HTG and OHT patients. Therefore, WDT has clinical significance in assessing fluctuations in patients' IOP.