Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

Objective:To analyze the efficacy and safety of low-dose azacitidine in the treatment of senile myelodys-plastic syndromes(MDS).Methods:A total of 92 elderly MDS patients who were initially diagnosed in the Huaibei Miners General Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2018 to June 2022 were randomly divided into the observation group and the control group with 46 patients in each group.The observation group received a low dose of azacitidine 100 mg/d,dl-7,28 days as a course of treatment,6 courses in total,and the control group received a standard dose of azacitidine 75 mg(m2·d),d1-7,28 days as a course of treatment,a total of 6 courses of treatment.The clinical efficacy,overall survival(OS)and adverse reactions of the two groups of patients were observed.Results:There was no statistically significant difference in the clinical data between the two groups(P＞0.05).After treatment,the hemoglobin and platelet levels of the two groups of patients were significantly higher than before treatment in each group(P＜0.05).There was no statistically significant difference in leukocyte,hemoglobin and platelet levels between patients in the observation group and control group(P＞0.05).The number of cases with complete remission,partial remission,hematological remission,disease stabilization and disease progression in the observation group were 4,10,22,6 and 4,respectively,with a total effective rate of 78.26％.The numbers of cases with complete remission,partial remission,hematological remission,disease stabilization and disease progression in control group were 8,12,18,4 and 4,respectively,with a total effective rate of 82.61％.The total effective rate of patients in the observation group was slightly lower than that of the control group(x2=0.457,P=0.254).There was no significant difference between the two treatment schemes in the treatment of patients with blood transfusion dependence and patients with low risk,medium risk and high risk(P＞0.05).It takes 4 and 6 courses of treatment to achieve the best treatment response in the control group and observation group respectively.There was no significant difference in OS between the two groups(P＞0.05).In the observation group,there were 4,6 and 2 cases of infection,Ⅲ-Ⅳ degree myelosuppression and gastrointestinal reaction,respectively,with the incidence rate of adverse events being 26.09％.In the control group,there were 6,16 and 6 cases of infection,Ⅲ-Ⅳ degree myelosuppression and gastrointestinal reaction,respectively,with the adverse event rate was 60.87％.The incidence of adverse events in the control group was significantly higher than that in the observation group(x2=7.095,P=0.036).Conclusion:Elderly patients with MDS have poor tolerance to chemotherapy.Reducing azacitidine in the treatment of elderly MDS patients shows good efficacy and safety.

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Quality Control ; Big Data ; Algorithms

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Calreticulin/genetics* ; DNA Methylation ; Female ; Humans ; Janus Kinase 2/genetics* ; Mutation ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera/genetics*

ObjectiveThe purpose of this study is to analyze the intraoperative and postoperative conditions of pediatric laparoscopy in fertility preservation in pubertal and prepubertal patients with β-thalassemia major （TM） and to further explore the prospects of pediatric laparoscopy in fertility preservation surgery. MethodsTotally 13 pubertal and prepubertal patients with β-TM who underwent ovarian tissue cryopreservation （OTC） combined with in vitro maturation （IVM） for fertility preservation through pediatric laparoscopic acquisition of ovarian tissue before hematopoietic stem cell transplantation were analyzed. ResultsAll 13 children underwent laparoscopic unilateral oophorectomy， with an average operative time of （58.31±20.25） minutes and an average intraoperative bleeding of （2.46±1.13） mL. All 13 children had no postoperative complications and an average hospital stay of （3.62±1.33） days. All children had ovarian tissue available for cryopreservation； the average pieces of ovarian tissue frozen was 7.77±2.31. Eleven of them also had mature oocytes available for cryopreservation； the average number of oocytes frozen was 4.92±4.27. ConclusionPediatric laparoscopic is a safe and effective fertility-preserving procedure that can be strongly promoted in pubertal and prepubertal patients with β-TM.

We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

ObjectiveTo investigate the value of micro- dissection testicular sperm extraction (micro-TESE) in the treatment of non-obstructive azoospermia (NOA) in patients with the history of secondary testicular injury.

METHODSTotally, 121 NOA patients with the history of secondary testicular injury underwent micro-TESE in our hospital from September 2014 to December 2017. We analyzed the correlation of the sperm retrieval rate with the causes of testicular injury and compared the outcomes of the ICSI cycles with the sperm retrieved from the NOA males by micro-TESE (the micro-TESE group) and those with the sperm ejaculated from severe oligospermia patients (sperm concentration <1×10⁶/ml, the ejaculate group). Comparisons were also made between the two groups in the female age, two-pronucleus (2PN) fertilization rate, transferrable embryos on day 3 (D3), D3 high- quality embryos, D14 blood HCG positive rate, embryo implantation rate, and clinical pregnancy rate.

RESULTSTesticular sperm were successfully retrieved by micro-TESE in 86.0% of the patients (104/121), of whom 98.4% had the history of orchitis, 75.5% had been treated surgically for cryptorchidism, and 63.6% had received chemo- or radiotherapy. No statistically significant differences were observed between the micro-TESE and ejaculate groups in the 2PN fertilization rate (59.4% vs 69.3%, P > 0.05), D14 blood HCG positive rate (44.6% vs 57.9%, P > 0.05), embryo implantation rate (31.8 %% vs 32.6%, P > 0.05) and clinical pregnancy rate (41.5% vs 48.7%, P > 0.05). However, the rate D3 transferrable embryos was significantly lower in the micro-TESE than in the ejaculate group (40.5% vs 52.2%,P < 0.05), and so was that of D3 high-quality embryos (32.5% vs 42.1%, P < 0.05).

CONCLUSIONSMicro-TESE can be applied as the first choice for NOA patients with the history of secondary testicular injury, but more effective strategies are to be explored for the improvement of ICSI outcomes with the sperm retrieved by micro- TESE.