Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib / 中国药房

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Mechanism of ginkgo flavonoid aglycone against doxorubicin-induced cardiotoxicity / 中国药房

OBJECTIVE To investigate the potential mechanism of the effect of ginkgo flavone aglycone （GA） against doxorubicin （DOX）-induced cardiotoxicity. METHODS The male ICR mice were randomized into control group （CON group）， model group （DOX group） and GA+DOX group （GDOX group）， with 12 mice in each group. The DOX group was injected with DOX solution at a dose of 3 mg/kg via tail vein every other day， and the GDOX group was given GA suspension intragastrically at a dose of 100 mg/kg every day+DOX solution at a dose of 3 mg/kg via tail vein every other day， for 15 consecutive days. After the end of administration， the serum levels of aspartate aminotransferase（AST）， creatine kinase（CK）， creatine kinase isoenzyme（CK- MB） and lactate dehydrogenase（LDH） in mice were detected in each group. Based on the metabolomics method， UHPLC-Q- Exactive Orbitrap HRMS method was used； based on principal component analysis （PCA） and orthogonal partial least squares- discriminant analysis （OPLS-DA）， the differentially expressed metabolites （DEMs） were screened using the criteria of variable importance in the projection≥1， fold change of peak area＞1 and P＜0.05； biological analysis was conducted based on databases such as HMDB and PubChem. RESULTS Compared with CON group， serum levels of AST， CK， CK-MB and LDH were increased significantly in DOX group （P＜0.05）； compared with DOX group， the serum levels of the above indicators （except for CK-MB） were decreased significantly in GDOX group （P＜0.05）. PCA and OPLS-DA showed that myocardial tissue samples of CON group， DOX group and GDOX group were isolated completely. After database matching， 37 common DEMs were identified， among which 17 DEMs were significantly up-regulated in the DOX group and significantly down- regulated in the GDOX group， and 8 DEMs were significantly down-regulated in the DOX group and significantly up-regulated in the GDOX group； pathway enrichment involved the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism， linoleic acid metabolism， taurine and hypotaurine metabolism； the key metabolites in the above pathways included docosahexaenoic acid， arachidonic acid， phosphatidylcholine （16∶0/18∶3） and taurine. CONCLUSIONS GA may regulate the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism and other metabolic pathways by acting on the core metabolites such as docosahexaenoic acid and arachidonic acid， thus alleviating the cardiotoxic effects of DOX.

Mechanism Exploration of TG Regulating PI3K/Akt to Improve Insulin Resistance in Liver of T2DM Rats Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangzhi pills on the improvement of insulin resistance （IR） in the liver with type 2 diabetes （T2DM） by regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway based on differential genes and its possible molecular mechanism. MethodT2DM rat models were prepared by high fat （HFD） diet combined with streptozotocin （STZ） intraperitoneal injection. The experiment was divided into blank group， model group， metformin hydrochloride group （0.18 g·kg-1）， Tangzhi pills high （1.08 g·kg-1）， medium （0.54 g·kg-1） and low （0.27 g·kg-1） dose groups. Rat serum， liver， and pancreatic tissue were collected， and the pathological tissue of the liver and pancreas was observed using hematoxylin-eosin （HE） staining. The fasting blood glucose level （FBG） was detected， and oral glucose tolerance （OGTT） tests were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS） and glycated hemoglobin （GHb） levels in rats. IR homeostasis model index （HOMA-IR）， β cellular homeostasis index （HOMA-β）， and insulin sensitivity index （ISI） were calculated. Biochemical methods were used to determine the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL-C）， and high-density lipoprotein （HDL-C） in rat serum. Transcriptomics obtained differentially expressed mRNA from liver tissue and enriched differentially expressed pathways. Real-time reverse transcriptase polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of cyclic adenylate responsive element binding protein 3-like protein 2 antibody （CREB3l2）， B-lymphocyte tumor 2 （Bcl-2）， Toll-like receptor 2 （TLR2）， cyclin-dependent kinase inhibitor 1A （CDNK1A）， and DNA damage induced transcription factor 4-like protein （DDIT4） in liver tissue. Western blot was used to detect the protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， glucose transporter 4 （GLUT4）， insulin receptor （INSR）， and insulin receptor substrate 2 （IRS2）. ResultThe pharmacodynamic experiment results showed that compared with model group， Tangzhi pills groups repaired liver and pancreatic tissue to varying degrees， reduced blood sugar （P<0.01）， and promoted a decrease in serum FINS， GHb， and HOMA-IR （P<0.05， P<0.01）. In addition， HOMA-β and ISI increased （P<0.05， P<0.01）. The levels of TC， TG， and LDL-C decreased （P<0.05， P<0.01）， while the levels of HDL-C increased （P<0.05， P<0.01）. The transcriptomics experimental results confirmed that the PI3K/Akt signaling pathway was significantly expressed in both the blank group and model group， as well as in the high-dose Tangzhi pills group and model group. CDNK1A， DDIT4， CREB3l2， Bcl-2， and TLR2 were significantly differentially expressed mRNA during TG intervention in T2DM. Compared with the model group， the protein expression of p-PI3K， p-Akt， GLUT4， INSR， and IRS2 increased in all Tangzhi pills groups （P<0.01）. The mRNA expression of CREB3l2， Bcl-2， and TLR2 increased （P<0.01）， while that of CDNK1A and DDIT4 decreased （P<0.01）. ConclusionTangzhi pills may regulate the PI3K/Akt signaling pathway based on the differential mRNA expression of CREB3l2， Bcl-2， TLR2， CDNK1A， and DDIT4， thereby improving IR in the liver with T2DM.

Risk factors for delayed bleeding after intestinal polypectomy in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics and risk factors of delayed bleeding after intestinal polypectomy in children, and to provide a theoretical basis for clinical surgical intervention of intestinal polyps.@*METHODS@#A retrospective analysis was conducted on the clinical data of 2 456 children with intestinal polyps who underwent endoscopic high-frequency electrocoagulation loop resection in the Endoscopy Center of Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. According to the presence or absence of delayed bleeding after surgery, they were divided into bleeding group with 79 children and non-bleeding group with 2 377 children. A multivariate logistic regression analysis was used to investigate the risk factors for delayed bleeding. The receiver operating characteristic (ROC) curve was used to investigate the value of various indicators in predicting delayed bleeding.@*RESULTS@#Of all 2 456 children, 79 (3.22%) experienced delayed bleeding, among whom 5 children with severe delayed bleeding underwent emergency colonoscopy for hemostasis and 74 received conservative treatment, and successful hemostasis was achieved for all children. There were significant differences between the bleeding and non-bleeding groups in age, body mass index, constipation rate, location of lesion, time of endoscopic procedure, resection method (P<0.05). Children with a diameter of polyps of 6-10 mm and >20 mm were more likely to develop delayed bleeding after resection (P<0.05). The multivariate logistic regression analysis showed that endoscopic operation time, polyp diameter, and resection method were significantly associated with delayed bleeding (P<0.05). The ROC curve analysis showed that the endoscopic operation time, polyp diameter, and resection method had a good value in predicting delayed bleeding after intestinal polypectomy, with an area under the ROC curve of 0.706, 0.688, and 0.627, respectively.@*CONCLUSIONS@#Endoscopic high-frequency electrocoagulation loop resection has a lower incidence of delayed bleeding in children with intestinal polyps, and the endoscopic operation time, polyp diameter, and resection method are closely associated with the occurrence of postoperative delayed bleeding.

Clinical analysis of cervical lesions in 1 337 postmenopausal women diagnosed during screening / 中华老年医学杂志

Objective:To screen and diagnose cervical lesions in middle-aged and elderly postmenopausal women and analyze the characteristics of cervical lesions in middle-aged and elderly women.Methods:A retrospective analysis was conducted on the screening data of 1 337 postmenopausal women aged between 50 and 86 years who visited the outpatient clinics of the gynecology department of Beijing Hospital between January, 2015 and December, 2019.Participants were divided into groups based on age, with 787 in the 50-59 years old group, 483 in the 60-69 years old group, 60 in the 70-79 years old group, and 7 in the 80-89 years old group.Exfoliated cervical cells were collected, and high-risk human papillomavirus(HPV)detection and liquid-based cervical cytology examination were performed to confirm the diagnosis based on the pathological results of cervical biopsy.Cervical lesions were analyzed.Results:53.0%(708)of the 1 337 enrolled patients made their hospital visits because of symptoms.There were 666 patients(49.8%)with cervical lesions, including 357 with low-grade squamous intraepithelial lesions(LSIL), 252 with high-grade squamous intraepithelial lesions(HSIL)and 57(4.3%)with cervical cancer.The 70-79 group showed the highest incidence of HSIL at 30.0%(18/60), while the 50~59 group had the highest incidence of LSIL at 30.6%(241/787), and there were significant differences in different types of cervical lesions between different age groups( χ2=28.919, P<0.01). Liquid-based cervical cytology examination revealed a positive rate of 51.6%(166/322)for LSIL, a positive rate of 70.8%(143/202)for HSIL, and a rate of 71.4%(25/35)for cervical cancer.There were significant differences in LSIL, HSIL and other above-mentioned positive rates of lesions( P<0.05). In the cervical malignancy group, cytological high-grade squamous epithelial lesions made up 51.4%(18/35). Intraepithelial lesions or cancerous lesions represented 29.2%(59/202)in the HSIL group.The rate of intraepithelial lesions or cancerous lesions in the LSIL group was 48.4%(156/322), with statistically significance in these differences( χ2=118.806, P<0.01). Chronic cervicitis was found in 52.9%(109)of 206 patients with atypical squamous cells and positive HPV, and in 76.2%(16)of 21 patients without HPV.HPV examination was completed in 1 301 patients, with 69.4%(903)having infections by one HPV strain and 30.6%(398)having infections by mixed HPV strains.Biopsy results showed that the rates of HPV infections in LSIL, HSIL and cancer patients were 84.6%(302/357), 95.9(185/193)and 100%(54/54), respectively, and the differences in these pathological results were statistically significant( P<0.01). HPV16 was the most common subtype in single HPV strain infections.The most common subtypes of HPV infections in cervical lesions with HSIL and above were HPV16 and HPV18.The agreement rate was 52.4%(187/357)for LSIL, 60.7%(153/252)for HSIL, and 64.9%(37/57)for cervical cancer between diagnoses based on cervical biopsy and those based on colposcopy.As the severity of lesions increased, the accuracy of colposcopy also increased.Differences between colposcopic diagnosis and pathological diagnosis on different types of cervical lesions were statistically significant( χ2=550.382, P<0.01).1 310 patients underwent endocervical curettage, identifying 120 cases of HSIL and 39 cases of cervical cancer, with a detection rate of 55.8%(159/285). Conclusions:The incidence of cervical cancer is high in elderly women.The incidences of high-grade lesions and cervical cancer in patients with atypical squamous cells plus HPV infections in the cervix are also high.Postmenopausal patients with cervical lesions are mainly infected by a single HPV subtype, with subtype 16 being the most common one.With increasing severity of lesions, the accuracy of colposcopy-based diagnosis increases and the rate of missed diagnosis decreases.Cervical curettage is an important means to reduce missed diagnosis with colposcopy.

Meta-analysis of Radiomics to predict the efficacy of non-surgical treatment for esophageal cancer / 国际外科学杂志

Objective:To evaluate the value of radiomics in predicting the efficacy of non-operative treatment of esophageal cancer by meta-analysis.Methods:Search terms included "Esophageal Neoplasms", "Esophageal Neoplasms", "Neoplasm, Esophageal", "Esophagus Neoplasm", "Esophagus Neoplasm", "Neoplasm, Esophagus", "Neoplasms, Esophagus", "Neoplasms, Esophageal", "Cancer of Esophagus", "Cancer of the Esophagus", "Esophagus Cancer", "Cancer, Esophagus", "Cancers, Esophagus", "Esophagus Cancers", "Esophageal Cancer", "Cancer, Esophageal", "Cancers, Esophageal", "Esophageal Cancers" and "radiomics", "radiomics features", "radiomic", "texture", "texture analysis", "textural analysis", "histogram", "machine learning", "artificial intelligence", both in English and corresponding Chinese. The Chinese and English literatures related to radiomics prediction of the efficacy of non-surgical treatment of esophageal cancer published in PubMed, Web of Science, Embase, China National Knowledge Internet, Wanfang Medical Online and VIP Chinese Journal Service Platform from the establishment of the database to November 2022 were searched, and screening, quality evaluation and data extraction were carried out. Meta analysis was performed by using Stata 15.1, Meta-disc 1.4 and Review Manager 5.3 software.Results:Seventeen literatures of Chinese and English with 1389 patients with esophageal cancer who received non-surgical treatment were included. There was no significant threshold effect in predicting the effect of non-operative treatment of esophageal cancer by radiomics ( r=0.103, P=0.694), and there was high heterogeneity ( I2>50%). The combined sensitivity of all included literatures was 0.86 (95% CI: 0.81-0.89), specificity was 0.81 (95% CI: 0.76-0.85), positive likelihood ratio was 4.4 (95% CI: 3.5-5.6), and negative likelihood ratio was 0.18 (95% CI: 0.13-0.24). The diagnostic odds ratio was 25 (95% CI: 16-39) and the AUC was 0.90 (95% CI: 0.87-0.92). Conclusions:Radiomics can better predict the efficacy of non-surgical treatment of esophageal cancer, MRI and PET/CT radiomics has higher accuracy in predicting the efficacy of esophageal cancer, and machine learning can also improve the accuracy of prediction. It is helpful to make individualized treatment plan and improve the efficiency of treatment by effectively predicting the curative effect of patients with esophageal cancer before treatment.

Construction of Literature Knowledge Ontology for Traditional Chinese Medicine Clinical Trials： A Review / 中国实验方剂学杂志

ObjectiveTo effectively organize the interdisciplinary knowledge of traditional Chinese medicine （TCM） and evidence-based medicine contained in the clinical trial literature of TCM and facilitate the processing and mapping of multi-source data， this paper organized the knowledge of clinical trial literature of TCM by ontology modeling. MethodThe seven-step method and skeleton method were used to develop the ontology. After the structure and language characteristics of TCM clinical trial literature were analyzed， the ontological and non-ontological resources such as top-level framework of Scientific Evidence and Provenance Information Ontology （SEPIO） and TCM language system （TCMLS） were reused to determine the domain concepts and attribute relationship. Finally， the core concepts and attribute relationship such as disease， syndrome， symptom， grouping， intervention measures， outcome indicators and literature quality information were determined. ResultThe information contained in the clinical trial literature of TCM was divided into five categories. According to the Cochrane risk of bias assessment tool and CONSORT 2010 statement， the literature quality evaluation information was mapped to the ontology， and a total of 68 categories， 8 object attributes， and 38 data attributes were established， which basically realized the structured expression of clinical trial literature. ConclusionThe ontology of TCM clinical trial literature constructed in this study can well organize， utilize， and present the construction and association of internal knowledge system in TCM clinical trial literature， underpinning the reasoning of strength of evidence and information of diagnosis and treatment in the future.

Epidemiological characteristics and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City / 中国血吸虫病防治杂志

Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.

Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis.@*METHODS@#The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed.@*RESULTS@#The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L.@*CONCLUSION@#High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

The Role of miR-21 in Skin-related Diseases and Wound Healing / 中国生物化学与分子生物学报

microRNA-21(miR-21) is an endogenous non-coding RNA and plays a key regulatory role in the process of cell proliferation and differentiation. In recent years, miR-21, as a widely studied miRNA, has attracted much attention for its role in skin- related diseases and wound healing. The study shows that miR-21, as a " broad factor", affects the proliferation, apoptosis, migration and invasion of different cells (keratinocytes, T cells, fibroblasts, etc.) by inhibiting the transcription and translation of different target genes (PTEN, TIMP, PDCD4, etc.) . At the same time, it plays a crucial role in skin tumors, skin immune diseases, skin inflammatory diseases, skin wounds and scar tissue formation by promoting inflammation through different signaling pathways. In this study, we reviewed the regulatory roles of miR-21 in different skin diseases (melanoma, cutaneous squamous cell carcinoma, T-cell lymphoma, psoriasis, scleroderma, etc.) and wound healing, aiming at deepening the understanding of miR-21 molecule in skin-related diseases and wound healing. The potential of miR-21 as a biomarker for skin disease diagnosis and its ability to evaluate the efficacy of drugs were also discussed. miR-21 is expected to become a new target of skin disease and wound healing, which may provide a new direction for clinical research.

Relationship between Fok polymorphism of vitamin-D receptor gene and hypertensive disorder complicating pregnancy in Han nationality of Qinghai province / 解剖学报

[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (

Clinical efficacy and anti-inflammation/anti-fibrosis effect of tripterygium glycosides in the treatment of diabetic nephropathy / 中国临床药理学与治疗学

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ

Research progress of JAK/STAT signaling pathway in the intervention of diabetic microvascular complications / 中国临床药理学与治疗学

Diabetic microvascular complications are the main reason for the high mortality of diabetic patients. There is still a great shortage of existing therapeutic drugs, so there is an urgent need for more effective new drugs. Janus kinase/signal transducer and activator of transcription (JAK/STAT) is involved in the progression of diabetic microvascular complications, which can be improved by regulating this pathway. Therefore, this article reviews the progress of JAK/STAT in diabetic microvascular complications (diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy), and summarizes the potential drugs that intervene JAK/ stat to improve diabetic microvascular complications in recent years from three aspects of therapeutic drugs, preclinical drugs, and traditional Chinese medicine, in order to provide ideas for drug development and treatment of diabetic microvascular complications.

Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes / 中华妇产科杂志

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Study on incidence and disease burden of foreign body in eyes in 1990 and 2019 of China / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the incidence and disease burden of foreign body in eyes in 1990 and 2019 of China.METHODS: Using the global burden of disease database in 2019, the incidence and disability adjusted life years(DALY)of foreign body in eyes in 1990 and 2019 of China were analyzed among the total population and different age groups of China.RESULTS: In 2019, the number of cases of foreign body in eyes in China was 11.2535 million, and the incidence was 79.12/10 000. The number and incidence of foreign body in eyes in 2019 decreased 12.87% and 27.49% respectively compared with those in 1990. In 2019, the DALY of foreign body in eyes in China was 181 200 person-years, and the DALY of foreign body in eyes in 2019 increased by 6.14% compared with 1990. In 2019, the age groups with the highest number of cases, incidence and DALY were all 20-54 years old, which were 8 012 600, 103.97/10 000 and 102 500 person-years, respectively. From 1990 to 2019, the incidence of foreign body in eyes in China showed a decreasing trend, average annual percentage change(AAPC)=-1.2%(95%CI: -1.8～-0.7, P&#x0026;#x003C;0.05), and DALY rate also showed a decreasing trend, AAPC=-0.6%(95%CI:-2.1～0, P&#x0026;#x003C;0.05). From 1990 to 2019, the incidence and DALY rate of foreign body in eyes in China and the World showed a downward trend. In 2019, the incidence and DALY rate of foreign body in eyes in China were significantly higher than those in the World and regions with different sociodemographic index(SDI).CONCLUSION: Although the incidence and DALY rates of foreign body in eyes in China have been decreasing in recent years, China has a large population base and the burden of foreign body in eyes is still large in the World. Active preventive measures should be taken to reduce the disease burden of foreign body in eyes.

Optimized pathway to schistosomiasis elimination in China: a scrutiny using a marginal benefit approach / 中国血吸虫病防治杂志

Following concerted efforts for over 7 decades, great achievements have been gained in the national schistosomiasis control program of China. Currently, China is moving towards the stage of schistosomiasis elimination, when the major task is to make full use of available resources to improve schistosomiasis surveillance and response to sustainably consolidate gained schistosomiasis control achievements and prevent re-emerging schistosomiasis. There is therefore an urgent need for optimization of interventions for schistosomiasis elimination. Based on analysis of socioeconomic features at different stages of the national schistosomiasis control program in China, this review discusses the relationship between the needs of assessment of schistosomiasis elimination interventions and the optimized strategy of schistosomiasis elimination at different stages of the national schistosomiasis control program using a marginal benefit approach and proposes the optimized schistosomiasis elimination strategy that allows the highest marginal benefit with currently available schistosomiasis elimination costs, so as to provide the optimal strategic pathway to schistosomiasis elimination and facilitate the achievement of the targets set in Healthy China 2030.

Recent progress in delivery systems for photosensitizers and anti-cancer photodynamic therapy / 药学学报

Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.

Polysaccharide of Balanophora involucrata Hook. f. attenuates cell ferroptosis in rats with experimental liver injury through SLC7A11/GPX4 pathway / 药学学报

Polysaccharide of Balanophora involucrata Hook. f. (BPS), the major component of Balanophora involucrata Hook. f., was confirmed the protective effect on liver injury in our previous study. This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) pathway. The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines. Rats were given intraperitoneal injection of (D-galactosamine, D-GalN) solution (800 mg·kg-1) one time to establish the acute liver injury model. The results showed aspartate amino transferase (AST), alanine aminotransferase (ALT) and 4-hydroxynonenal (4-HNE) levels in serum were decreased, and the contents of reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA) and lipid peroxide (LPO) in liver tissues also decreased and glutathione (GSH) level increased after BPS administration with 200 mg·kg-1. Besides, BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue. In conclusion, BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway. The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

Expression of IGLL1 Gene and Its Clinical Significance in Pediatric T-ALL / 中国实验血液学杂志

OBJECTIVE@#To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.@*METHODS@#A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.@*RESULTS@#The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.@*CONCLUSION@#In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.