OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective:To evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To evaluate the efficacy and clinical application value of mouse nerve growth factor combined with neostigmine in the treatment of nerve injury in patients bitten by Bungarus multicinctus by a prospective single-blind controlled clinical study.Methods:In June 2020, a prospective, single-blindness, randomized grouping method was used to select patients with bungarus multicinctus saurogobio dabryi subsp. dabryi bite injuries admitted to the Emergency Department of Ganzhou People's Hospital in Jiangxi Province as the study subjects. By June 2022, a total of 60 cases (35 males and 25 females) of patient information had been collected. The patients were divided into two groups <4 h and ≥4 h after being bitten by bungarus multicinctus. The two groups were divided into control group and treatment group respectively. The treatment group was given an intramuscular injection of neostigmine 1mg q8 h and mouse nerve growth factor 18 μg/d based on conventional treatment. The control group was only given conventional treatment. Myasthenia Gravis Composite Scale (MGC) scores were performed for all patients at admission, 4 hours, 8 hours, and 24 hours. Muscle strength was continuously assessed and the recovery time of muscle strength was recorded. Quantitative data comparisons between groups at admission were analyzed using one-way ANOVA, while qualitative data comparisons were conducted using χ2 tests. Variables showing intergroup differences in baseline measurements (Parazacco spilurus subsp. spilurus) were treated as covariates, with treatment outcomes post-admission compared via analysis of covariance (ANCOVA). Pairwise comparisons of quantitative data between groups employed the Bonferroni method. Baseline quantitative data correlation analysis utilized Pearson correlation, followed by partial correlation analysis after controlling for grouping variables.Results:The MGS scores of the treatment group in both the ≥4 h and <4 h patient groups were lower than those of the control group at the same time points ( P<0.05). After adjusting for the influence of MGS scores at admission, the muscle strength recovery time in the ≥4 h treatment group was significantly shorter compared to the control group, with a statistically significant difference ( P<0.001). MGS scores at 4 h, 8 h, and 24 h after admission were positively correlated with muscle strength recovery time ( r=0.540, 0.720, 0.640, respectively, P<0.001). Muscle strength recovery time was positively correlated with disease duration ( r=0.910, P<0.001). Disease duration was positively correlated with MGS scores at admission ( r=0.908, P<0.001) and with muscle strength recovery time ( r=0.757, P<0.001). After controlling for grouping, the correlation coefficient increased, showing a strong correlation ( r=0.892, P<0.001) . Conclusion:The combination of mouse nerve growth factor and neostigmine can shorten the time of muscle weakness after the bite of Bungarus multicinctus, promote the recovery of injured nerves, and improve the clinical symptoms caused by nerve snake venom.

Objective:To investigate the risk factors associated with one-year mortality following surgery for intertrochanteric fractures in elderly patients and develop a survival prediction model.Methods:A retrospective analysis was conducted on clinical data from 532 elderly patients with intertrochanteric fractures admitted to the People's Hospital of Xinjiang Uygur Autonomous Region and the People's Hospital of Xinyang between January 2020 and September 2022.Patient demographics, laboratory indicators, and surgical variables were documented.The primary outcome assessed was the one-year mortality rate.Risk factors were identified through univariate and multivariate Cox regression analyses, leading to the development of a prognostic model.The model's predictive performance was evaluated using the Concordance Index(C-Index), time-dependent receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).Results:Multivariate Cox regression analysis identified several key factors associated with one-year mortality after intertrochanteric fractures in elderly patients.These factors included the modified five-item frailty index( OR=1.338, 95% CI: 1.147-1.561, P<0.001), ICU admission( OR=1.694, 95% CI: 1.230-2.333, P=0.001), preoperative hemoglobin levels( OR=1.281, 95% CI: 1.016-1.616, P=0.036), surgical waiting time( OR=1.570, 95% CI: 1.063-2.319, P=0.023), and age( OR=2.196, 95% CI: 1.712-2.816, P<0.001).The prediction model showed good consistency with a C-Index of 0.769(95% CI: 0.723-0.818)in the modeling group and 0.715(95% CI: 0.612-0.750)in the validation group.Time-dependent ROC areas under the curve were 0.802(95% CI: 0.722-0.850)and 0.718(95% CI: 0.640-0.808)for the modeling and validation groups, respectively.Calibration curves for both groups indicated a good model fit, and decision curve analysis demonstrated a positive net benefit, highlighting the clinical applicability of the model. Conclusions:The modified five-item frailty index, ICU admission, preoperative hemoglobin, surgical waiting time, and age independently predict one-year mortality after surgery for intertrochanteric fractures in elderly patients.This prognostic model, utilizing these factors, shows high predictive accuracy, assisting clinicians in quick personalized assessments and setting informed expectations in clinical practice.

The patient was diagnosed with "motor retardation for 3 years" in the neurology department of our hospital,accompanied by static tremors and ataxia. Physical examination showed that there was a tendency to decrease for amplitude of repetitive finger movements of the left hand and the left hand clenched fist and toe tapping movements were slightly slower. The left heel knee tibia test and rotation test were not accurate,and the father and elder sister had similar symptoms. After admission,laboratory tests such as urinary tract ultrasound and residual urine in the bladder were completed,and the tests did not reveal any significant abnormalities. Brain MRI shows scattered non-specific white matter changes in the left parietal lobe. Levodopa challenge test was positive. The patient was then suspected to have Parkinsonism. considering that the patient has a family history. Genetic testing was ordered and the results showed abnormal amplification of the ATXN2 gene CAG sequence. Therefore,the final diagnosis was spinocerebellar ataxia type 2. The patient's symptoms are stable and there is no progression during the follow-up. SCA2 should be considered in the case of Parkinsonism accompanied by ataxia and a family history to avoid misdiagnosis and missed diagnosis.

The patient was diagnosed with "motor retardation for 3 years" in the neurology department of our hospital,accompanied by static tremors and ataxia. Physical examination showed that there was a tendency to decrease for amplitude of repetitive finger movements of the left hand and the left hand clenched fist and toe tapping movements were slightly slower. The left heel knee tibia test and rotation test were not accurate,and the father and elder sister had similar symptoms. After admission,laboratory tests such as urinary tract ultrasound and residual urine in the bladder were completed,and the tests did not reveal any significant abnormalities. Brain MRI shows scattered non-specific white matter changes in the left parietal lobe. Levodopa challenge test was positive. The patient was then suspected to have Parkinsonism. considering that the patient has a family history. Genetic testing was ordered and the results showed abnormal amplification of the ATXN2 gene CAG sequence. Therefore,the final diagnosis was spinocerebellar ataxia type 2. The patient's symptoms are stable and there is no progression during the follow-up. SCA2 should be considered in the case of Parkinsonism accompanied by ataxia and a family history to avoid misdiagnosis and missed diagnosis.

Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite, SN-38. Unfortunately, the limited utility of irinotecan is attributed to its pH-dependent stability, short half-life and dose-limiting toxicity. To address this problem, a novel trivalent PEGylated prodrug (PEG-[Irinotecan]₃) has been synthesized and its full-profile pharmacokinetics, antitumor activity and toxicity compared with those of irinotecan. The results show that after intravenous administration to rats, PEG-[Irinotecan]₃ undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]_3‒x (x = 1,2) and PEG-[linker] during which time the released irinotecan undergoes conversion to SN-38. As compared with conventional irinotecan, PEG-[Irinotecan]₃ displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life. In a colorectal cancer-bearing model in nude mice, the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]₃ were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan. In summary, PEG-[Irinotecan]₃ displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan]₃ is a superior anticancer drug to irinotecan and it has entered the phase II trial stage.

Objective: To carry out a investigation on molecular epidemiological features of tick-borne Brucella in Xinjiang Uygur Autonomous Region (Xinjiang), and to provide a scientific basis for formulation of effective preventive and control measures. Methods: In 2016-2018, parasitic ticks (including engorged females) were collected on the body surface of livestock in 10 counties (cities) along the border of Xinjiang. The free-living ticks were collected by flagging method in Alashankou. The engorged female was placed in a breathable insect tube for spawning, each egg batch was divided into two parts: one part was tick eggs, while the second part was allowed further larval development. All ticks were identified by molecular biology (16S rRNA) identification. Tick DNA was extracted, PCR was performed based on Brucella omp22 and IS711, and amplification products were sequenced and analyzed by BLAST. Results: A total of 1 084 ticks were collected in 11 counties (cities), of them 747 were parasitic ticks (including 34 engorged females) and 337 were free-living ticks. Based on 16S rRNA identification, 1 084 ticks belonged to 4 genera and 5 species, and the proportions of Dermacentor nuttalli, Dermacentor marginatus, Haemaphysalis punctata, Hyalomma asiaticum and Rhipicephalus turanicus were 29.43% (319/1 084), 16.51% (179/1 084), 10.42%(113/1 084), 37.27% (404/1 084), and 6.37% (69/1 084), respectively. A total of 214 Brucella-positive nucleic acid samples were detected, the positive rate was 19.74%. The parasitic ticks' positive rate was 25.30% (189/747), and the free-living ticks' positive rate was 7.42% (25/337), parasitic ticks' positive rate was higher than that of free-living ticks (χ²=46.873, P < 0.05). Two Brucella melitensis nucleic acid samples were detected in 34 "engorged females-tick eggs" developmental stage, and one Brucella melitensis nucleic acid sample was detected in 22 "tick eggs-larvae" developmental stage. Conclusions Brucella is widely distributed in parasitic ticks and free-living ticks in Xinjiang border areas, and the parasitic ticks' positive rate is obviously higher than that of free-living ticks. The Brucella melitensis has potential transovarian transmission and transstadial transmission in ticks. In the prevention and control of livestock brucellosis, the work of killing ticks should be strengthened, including parasitic ticks on the body surface and free-living ticks in the environment.

BACKGROUND:A short-peptide small molecule hydrogel (SMH) developed in the previous study has more obvious advantages than other hydrogels to improve local microenvironment, carry bioactive substances and interfere with stem cell signal transduction pathways. OBJECTIVE:To explore the effect of SMHs on bone marrow mesenchymal stem cells (BMSCs) proliferation, apoptosis and differentiation into myocardial cells. METHODS: (1) Passage 9 rat BMSCs in vitro were divided into control group and experimental group, followed by routine culture and culture in SMHs, respectively. At 7 days of culture, cell proliferation and apoptosis were detected. Cells in the two groups were exposed to anaerobic environment for 12 hours, and expression levels of Bcl-2, Bax and Caspase-3 in BMSCs were detected. (2) Passage 9 BMSCs were divided into four groups and then cultured in 5-azacytidine, SMHs, SMHs+5-azacytidine, and L-DMEM (normal control), respectively. After 4 weeks of induction, expression of CTnT, desmin and Cx-43 proteins was detected and expression levels of early cardiac transcription factors, NKX2.5 and GATA-4, were also measured. RESULTS AND CONCLUSION: (1) Compared with the control group, better proliferation and lower apoptosis of BMSCs were found in the experimental group. Under anaerobic conditions, the number of survival cells was reduced in both groups, but less apoptosis or necrosis was found in the experimental group than the control group (P < 0.05). Moreover, the level of Bcl-2 was higher in the experimental group than the control group (P < 0.01), while the levels of Bax and Caspases-3 protiens were lower in the experimental group than the control group (P < 0.01). (2) NKx2.5 and GATA-4 mRNA expression was found in both 5-azacytidine and SMHs+5-azacytidine groups, and moreover, the mRNA levels of early cardiac transcription factors were significantly higher in the SMHs+5-azacytidine group than in the 5-azacytidine group (P < 0.05). In the normal control group, cTnT expressed negatively, and desmin and Cx-43 expressed weakly. The expression of cTnT, desmin and Cx-43 proteins was higher in the SMHs+5-azacytidine group than in the 5-azacytidine and SMHs groups, while there was no significant difference between the latter two groups. To conclude, SMHs as a culture medium is conducive to the proliferation of BMSCs, reduces cell apoptosis, and promotes myocardial differentiation of BMSCs.