Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective To explore the application effect of recombinant human granulocyte colony stimulating factor(rhG-CSF)in the treatment of chemotherapy-induced oral mucositis in children.Methods Totally 60 children with chemotherapy-induced oral mucositis who underwent chemotherapy in the tumor surgery of our hospital from January 2020 to June 2022 were randomly divided into two groups,30 cases each.The control group was given physiological saline oral care,and the experimental group was given rhG-CSF oral care.Compare the intervention effect,oral mucositis grading,quality of life[short form of health survey(SF-36)]and nursing satisfaction of parents of the two groups.Results The total effective rate of the experimental group was higher than that of the control group(P<0.05).After 5 days of intervention,the score of oral mucositis in the experimental group was better than that in the control group(P<0.05).After 5 days of intervention,the SF-36 score of children in the two groups was higher than that before intervention,and that in the experimental group was higher than that in the control group(P<0.05).The parents'satisfaction in the experimental group was higher than that in the control group(P<0.05).Conclusion rhG-CSF oral care can effectively improve the intervention effect of chemotherapy-induced oral mucositis in children,reduce the grade of oral mucositis,improve the quality of life of children,and improve the nursing satisfaction of parents of children.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease （CKD） and the effect of the therapy on the neutrophil-to-lymphocyte ratio （NLR） as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories， while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment， the clinical efficacy was assessed based on the changes in traditional Chinese medicine （TCM） symptom scores， renal function indicators， and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment （P<0.01）， and the decreases were more significant in the observation group than in the control group （P<0.05）. The total response rate of TCM symptoms in the observation group was 79.31% （23/29）， which was higher than that （62.96%， 17/27） in the control group （Z=0.604，P<0.05）. ② After treatment， the observation group showed declined serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， and cystatin C （Cys C） and increased glomerular filtration rate （GFR） （P<0.01）， and the control group showed lowered SCr level and increased GFR （P<0.05）. The observation group had lower SCr level and higher GFR than the control group after treatment （P<0.05）. The total response rate of renal function in the observation group was 79.31% （23/29）， which was higher than that （55.56%， 15/27） in the control group （Z=1.127，P<0.01）. ③ The NLR in the observation group decreased after treatment （P<0.05）， and it was lower than that in the control group （P<0.05）. ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.

ObjectiveTo observe the clinical efficacy and safety of Chaihu Shugansan combined with Xuanfu Daizhetang （CHSG-XFDZ） in the management of Barrett's esophagus （BE） with liver-stomach disharmony. MethodA randomized， parallel， controlled， double-blind clinical trial was conducted. BE patients who met the inclusion criteria were randomized into an observation group and a control group， with 34 patients in each group. The observation group was treated with CHSG-XFDZ combined with omeprazole capsules， and the control group was treated with CHSG-XFDZ mimetic combined with omeprazole capsules. Both groups were treated for 12 weeks. The traditional Chinese medicine （TCM） symptom scores， response rate， BE lesion area， BE pathological changes， and bile acid profile were taken as the indicators to jointly evaluate the clinical efficacy and safety of the two groups. ResultA total of 62 patients who completed the trial were included for statistical analysis， including 32 in the observation group and 30 in the control group. There were no statistically significant differences in baseline demographics or disease characteristics between two groups， which suggested that the two groups were comparable. The total response rate in the observation group was 93.7% （30/32）， which was higher than that （60.0%， 18/30） in the control group （χ²=24.766， P<0.05）. After treatment， the response rate regarding the pathological changes in the observation group was 62.5% （20/32）， which was higher than that （23.3%， 7/30） in the control group （χ²=10.270， P<0.05）. The response rate regarding the BE lesion area change in the observation group was 21.9% （7/32）， which had no statistically significant difference from that （6.7%， 2/30） in the control group， which indicated that the advantages of the two regimens were not obvious in terms of reducing the area of BE lesions. Compared with the control group after treatment， the observation group regulated the bile acid profile， which pointed out the direction for further exploring the mechanism of CHSG-XFDZ in treating BE. Neither group showcased adverse reactions with clinical significance during the treatment period. ConclusionCHSG-XFDZ outperformed the control group in terms of alleviating TCM symptoms， ameliorating pathological changes， and improving the bile acid profile in the BE patients with liver-stomach disharmony. It demonstrates certain potential in reducing the lesion area. This formula is safe and effective in treating BE patients with liver-stomach disharmony and deserves further clinical research and widespread application.

BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.

BACKGROUND:Ischemic postconditioning is one of the effective ways to reduce ischemia-reperfusion injury and has been more and more widely used in clinical practice in recent years,but its specific molecular mechanism has yet to be studied. OBJECTIVE:To investigate the role and mechanism of piRNA-005854 in the aging cardiomyocytes caused by hypoxic postconditioning. METHODS:In vitro,cardiomyocytes were administered 8 mg/mL D-galactose for 9 days to induce their aging.β-Galactosidase staining was used to observe the aging of cardiomyocytes.Senescent cells were treated with hypoxia/reoxygenation and hypoxic postconditioning.ELISA was utilized to detect changes in myocardial injury markers creatine kinase isoenzyme MB and lactate dehydrogenase levels.Western blot assay was applied to detect the expression changes of autophagy-related proteins LC3II,p62,ULK1 and phosphorylated ULK1 in aging cardiomyocytes.qRT-PCR was employed to determine the expression level of piRNA-005854.piRNA-005854 inhibitor and piRNA-005854 mimics were transferred into aging cardiomyocytes and followed with hypoxic postconditioning.Western blot assay was used to examine the expression of LC3II,p62,ULK1 and phosphorylated ULK1. RESULTS AND CONCLUSION:(1)D-galactose induced obvious senescence of cardiomyocytes 9 days later.(2)Compared with the normoxia group,creatine kinase isoenzyme MB and lactate dehydrogenase levels increased in the hypoxia/reoxygenation group(P<0.01);LC3 II/I expression was increased;p62 expression was decreased;ULK1 phosphorylation level was increased,and piRNA-005854 expression was increased(P<0.01).(3)Compared with the hypoxia/reoxygenation group,creatine kinase isoenzyme MB and lactate dehydrogenase levels significantly reduced in the hypoxic postconditioning group(P<0.01);LC3 II/I expression significantly decreased(P<0.05);p62 expression increased(P<0.01);ULK1 phosphorylation level decreased(P<0.05),and piRNA-005854 expression decreased(P<0.01).(4)After transfection of piRNA-005854 inhibitor,LC3II/I expression was decreased(P<0.01);the expression of p62 was increased significantly(P<0.05);the phosphorylation level of ULK1 was decreased significantly(P<0.01).After transfection of piRNA-005854 mimics,LC3II/I expression was increased significantly;the expression of p62 was decreased,and the phosphorylation level of ULK1 was increased significantly(P<0.01).(5)The results show that piRNA-005854-mediated reduction of ULK1-dependent autophagy level is a possible mechanism that hypoxic postconditioning exerts its protective effect on aging cardiomyocytes.