ObjectiveTo establish a tumor prognostic risk assessment model related to target genes of the miR-34 family. MethodsTarget genes of the miR-34 family were screened， and the scores of miR-34 target genes were assessed in 16 tumor types. Univariate Cox regression analysis was used to identify the tumor type with the strongest correlation between miR-34 target gene scores and overall survival （OS）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to elucidate the functional roles and signaling pathways of miR-34 target genes. A prognostic risk model based on the miR-34 target genes was constructed using univariate Cox and LASSO regression analyses. Quantitative real-time PCR （qPCR） and dual-luciferase reporter assays were conducted to validate whether the target genes bind to miR-34 and measure their RNA expression levels in the relevant tumors. Additionally， the risk score was integrated with other clinical indicators to develop a nomogram prediction model for patient survival. ResultsA total of 65 target genes of the miR-34 family were screened. The cancer type exhibiting stronger correlation between the target gene scores and OS was lung adenocarcinoma （P = 0.003， HR= 5.150）. Furthermore， miR-34 target genes were predominantly enriched in oxidative stress pathways and various tumor-related processes. Three genes， LDHA， GALNT7， and SATB2， were identified as core components of the prognostic analysis model for lung adenocarcinoma. Additionally， the constructed nomogram model demonstrated robust predictive performance. ConclusionThe risk model and prognosis model of lung adenocarcinoma constructed based on the key target genes of miR-34 have good predictive performance.

Objective Study on the effect of DNA methyltransferase 3A(DNMT3A),fat atypical cadherin 1(FAT1),and interleukin-7 receptor(IL-7R)gene mutations on the prognosis of patients with myelodysplastic syndrome(MDS)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)treatment with normal karyotype.Methods A single-center retrospective cohort method was used to analyze the clinical data of 380 patients with MDS with normal karyotype who received allo-HSCT to the Department of Hematology,Handan First Hospital from January 2021 to December 2023.Next-generation sequencing(NGS)was used to analyze the gene mutation profile of patients.According to the gene sequencing results,patients with any gene mutation in DNMT3A,FAT1 and IL-7R were classified as mutant group(n=61),and the remaining patients without the above mutation were included in the wild type group(n=319).The clinical characteristics of mutant and wild type patients were analyzed.Kaplan-Meier method was used to analyze the cumulative survival of mutant and wild-type patients,and Log Rank test was used to compare the differences between groups.According to the follow-up outcome,the patients were divided into death group(n=130)and survival group(n=250).Univariate and multivariate COX regression analysis of the factors affecting the overall survival time of MDS patients after allo-HSCT treatment.Results Among 380 patients with normal MDS,16.05%(61/380)were mutant.Compared with the wild type,the mutant's age years old,mean platelet volume(MPA)and IL-6 levels were significantly increased,and the differences were statistically significant(t=7.320,23.774,17.838,all P<0.05).There was no significant difference in overall survival(OS)rate between mutant group and wild-type group patients(59.02%vs 67.08%),and the difference was statistically significant(Log rank χ2=1.610,P>0.05).Age,sex,IL-6,DIF gene mutation,MPV,and bone marrow original cell ratio were the factors influencing the overall survival time of MDS patients after allo-HSCT treatment(t/χ2=5.286～42.498,all P＜0.05).COX regression analysis showed that bone marrow original cell ratio≥50%was an independent risk factor for overall survival of MDS patients after allo-HSCT treatment(95%CI:1.046～2.829,HR=1.734,P=0.026).Conclusion DNMT3A,FAT1 and IL-7R gene mutations have no significant effect on the overall survival of MDS patients with normal karyotype treated with allo-HSCT,and the proportion of bone marrow original cells is higher than 50%as an independent risk factor.

Objective Study on the effect of DNA methyltransferase 3A(DNMT3A),fat atypical cadherin 1(FAT1),and interleukin-7 receptor(IL-7R)gene mutations on the prognosis of patients with myelodysplastic syndrome(MDS)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)treatment with normal karyotype.Methods A single-center retrospective cohort method was used to analyze the clinical data of 380 patients with MDS with normal karyotype who received allo-HSCT to the Department of Hematology,Handan First Hospital from January 2021 to December 2023.Next-generation sequencing(NGS)was used to analyze the gene mutation profile of patients.According to the gene sequencing results,patients with any gene mutation in DNMT3A,FAT1 and IL-7R were classified as mutant group(n=61),and the remaining patients without the above mutation were included in the wild type group(n=319).The clinical characteristics of mutant and wild type patients were analyzed.Kaplan-Meier method was used to analyze the cumulative survival of mutant and wild-type patients,and Log Rank test was used to compare the differences between groups.According to the follow-up outcome,the patients were divided into death group(n=130)and survival group(n=250).Univariate and multivariate COX regression analysis of the factors affecting the overall survival time of MDS patients after allo-HSCT treatment.Results Among 380 patients with normal MDS,16.05%(61/380)were mutant.Compared with the wild type,the mutant's age years old,mean platelet volume(MPA)and IL-6 levels were significantly increased,and the differences were statistically significant(t=7.320,23.774,17.838,all P<0.05).There was no significant difference in overall survival(OS)rate between mutant group and wild-type group patients(59.02%vs 67.08%),and the difference was statistically significant(Log rank χ2=1.610,P>0.05).Age,sex,IL-6,DIF gene mutation,MPV,and bone marrow original cell ratio were the factors influencing the overall survival time of MDS patients after allo-HSCT treatment(t/χ2=5.286～42.498,all P＜0.05).COX regression analysis showed that bone marrow original cell ratio≥50%was an independent risk factor for overall survival of MDS patients after allo-HSCT treatment(95%CI:1.046～2.829,HR=1.734,P=0.026).Conclusion DNMT3A,FAT1 and IL-7R gene mutations have no significant effect on the overall survival of MDS patients with normal karyotype treated with allo-HSCT,and the proportion of bone marrow original cells is higher than 50%as an independent risk factor.

Objective To explore the mechanism of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]in renal interstitial fibrosis mediated by nuclear factor κB(NF-κB)and inflammatory cytokines.Methods Taking the renal interstitial fibrosis model induced by transforming growth factor-β1(TGF-β1)as the research object,they were divided into blank group(HK-2 cells+complete culture medium),model group(5ng/ml TGF-β1 stimulated HK-2 cells for 48 hours),intervention group A[with 10-7mol/L 1,25(OH)2D3 intervention for 24 hours on the basis of model group],intervention group B[with 10-7mol/L 1,25(OH)2D3 intervention for 48 hours on the basis of model group]and intervention group C[with 10-7mol/L 1,25(OH)2D3 intervention for 72 hours on the basis of model group].The cell morphology,activity,protein expression and inflammatory factor levels of each group were observed and compared.Results The cell viability of model group was significantly lower than that of blank group(P＜0.05),the cell viability of intervention groups A,B and C was significantly higher than that of model group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and smooth muscle actin α(α-SMA),as well as the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)in model group were significantly higher than those in blank group,while the protein expression of E-cadherin was significantly lower than that in blank group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and α-SMA,as well as the levels of IL-6 and TNF-α in intervention groups A,B and C were significantly lower than those in model group,while protein expression of E-cadherin was significantly higher than that in model group(P＜0.05).Among them,the change in intervention group A was the most significant.Conclusion 1,25(OH)2D3 can alleviate renal interstitial fibrosis by regulating the NF-κB signaling pathway and inflammatory cytokines,and 24 hours may be the optimal intervention time window.

Catalpol,the primary active component of Rehmannia glutinosa,exhibits potent antioxidant and anti-inflammatory effects and regulatory effects on glucose and lipid metabolism.This article systematically reviews recent studies on the impact of catalpol in addressing glycolipid metabolic disorders and related diseases and the underlying mechainsms.Catalpol can correct glucose and lipid metabolism imbalances to prevent the development and progression of diabetes complications including macrovascular and microvascu-lar diseases,through modulating the adenosine 5'-monophosphate-activated protein kinase signaling pathway to regulate lipogenesis and fat oxidation and altering the phosphorylation of forkhead transcription factor 1 and glycogen synthase kinase 3 to influence glyco-gen synthesis and breakdown.Catalpol plays a protective role in the cardio-cerebrovascular system,renal function,and retinal struc-ture and function through mediating signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B and oxidized low-density lipoprotein/lectin-like oxidized low-density lipoprotein receptor-1.By suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and endoplasmic reticulum stress,catalpol can alleviate inflammatory responses,thereby mitigat-ing inflammation-induced insulin resistance and glycolipid metabolic disorders.

Objective To explore the mechanism of 1,25-dihydroxy vitamin D3[1,25(OH)2D3]in renal interstitial fibrosis mediated by nuclear factor κB(NF-κB)and inflammatory cytokines.Methods Taking the renal interstitial fibrosis model induced by transforming growth factor-β1(TGF-β1)as the research object,they were divided into blank group(HK-2 cells+complete culture medium),model group(5ng/ml TGF-β1 stimulated HK-2 cells for 48 hours),intervention group A[with 10-7mol/L 1,25(OH)2D3 intervention for 24 hours on the basis of model group],intervention group B[with 10-7mol/L 1,25(OH)2D3 intervention for 48 hours on the basis of model group]and intervention group C[with 10-7mol/L 1,25(OH)2D3 intervention for 72 hours on the basis of model group].The cell morphology,activity,protein expression and inflammatory factor levels of each group were observed and compared.Results The cell viability of model group was significantly lower than that of blank group(P＜0.05),the cell viability of intervention groups A,B and C was significantly higher than that of model group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and smooth muscle actin α(α-SMA),as well as the levels of interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)in model group were significantly higher than those in blank group,while the protein expression of E-cadherin was significantly lower than that in blank group(P＜0.05).The protein expressions of p-NF-κBp65/NF-κBp65 and α-SMA,as well as the levels of IL-6 and TNF-α in intervention groups A,B and C were significantly lower than those in model group,while protein expression of E-cadherin was significantly higher than that in model group(P＜0.05).Among them,the change in intervention group A was the most significant.Conclusion 1,25(OH)2D3 can alleviate renal interstitial fibrosis by regulating the NF-κB signaling pathway and inflammatory cytokines,and 24 hours may be the optimal intervention time window.

OBJECTIVE: To summarize the clinical features, surgical methods, and prognosis of bucket-handle meniscal tears (BHMTs), and provide guidance for clinical treatment. METHODS: The clinical data of 91 BHMTs patients (91 knees), who met the selection criteria and were admitted between January 2015 and January 2021, was retrospectively analyzed. There were 68 males and 23 females. Age ranged from 16 to 58 years with an average of 34.4 years. The injury was caused by sports in 68 cases, traffic accident in 15 cases, and falls or sprains in 8 cases. There were 49 cases of left knee injury and 42 cases of right knee injury. The time from the onset of symptoms to the admission ranged from 1 day to 13 months (median, 18 days), including >1 month in 35 cases and ≤1 month in 56 cases. Medial BHMTs occurred in 52 cases and lateral BHMTs in 39 cases. There were 36 cases with ACL rupture and 12 cases with discoid meniscus. The knee extension was limited more than 10° in 55 cases. According to the condition of meniscus injury, the meniscus suture with Inside-out combined with All-inside techniques (54 cases) or meniscoplasty (37 cases) under arthroscopy were selected. ACL reconstruction was performed in all patients with ACL rupture with autogenous hamstring tendon. Postoperative complications were observed. International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner score were used to evaluate knee function, and clinical failure was recorded. RESULTS: Two patients developed intermuscular venous thrombosis, which improved after oral anticoagulant therapy. No vascular injury, postoperative infection, joint stiffness, or other complications occurred in all patients. All patients were followed up 24-95 months, with a median of 64 months. A total of 12 cases (13.19%) failed the operation and were re-operated or given oral anti-inflammatory analgesics and rehabilitation therapy. At last follow-up, IKDC score and Lysholm score of 91 patients significantly increased when compared with those before operation ( P<0.05), while Tegner score significantly decreased ( P<0.05). The above indexes of patients treated with meniscus suture and meniscoplasty were also significantly different from those before operation ( P<0.05). CONCLUSION BHMTs occurs mostly in young men and is one of the important reasons for the limitation of knee extension after trauma. Arthroscopic meniscus suture and meniscoplasty can obtain good effectiveness according to individual conditions of patients. But the latter can better preserve the shape and function of meniscus, and theoretically can obtain better long-term outcomes, which needs to be confirmed by further research with larger sample size.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Treatment Outcome ; Retrospective Studies ; Meniscus ; Knee Joint/surgery* ; Menisci, Tibial/surgery* ; Knee Injuries/diagnosis* ; Rupture ; Tibial Meniscus Injuries/surgery* ; Arthroscopy/methods* ; Anterior Cruciate Ligament Injuries/surgery*

To explore the incidence and grade of acute gastrointestinal injury（AGI）in patients with acute stroke，and the influence of gastrointestinal disorders on the mortality of stroke. Methods A total of 103 patients were recruited. According to the National Institutes of Health Stroke Scale（NIHSS）scores，they were divided into two groups：severe stroke patients（n=52）and mild to moderate stroke patients（n=51）.The incidence of gastrointestinal complications in the two groups are calculated. AGI classification was performed according to gastrointestinal symptoms. Binary logistic analysis was used to analyze the influencing factors of gastrointestinal failure in stroke patients，and KM curve was used to evaluate the effect of AGI classification on 28-day mortality in stroke patients. Results The incidence of gastrointestinal complications was 91.3%. There was no significant difference in the incidence of gastrointestinal disorders in the mild to moderate stroke and severe stroke groups（74.5% vs 75.0%，P>0.05）；The severe stroke group showed a higher incidence of gastrointestinal failure（7.8% vs 25.0%，P<0.05）. Multivariate logistic regression analysis showed：elevated NIHSS score was a risk factor for gastrointestinal failure after stroke（P<0.05）.Combining gastrointestinal failure significantly increased the 28-day mortality of stroke patients（χ2=53.08，P<0.001）. Conclusion Gastrointestinal complications are common in patients with acute stroke. NIHSS score is positively correlated with gastrointestinal failure. And patients with gastrointestinal failure have a worse prognosis.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.