Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification / 中国中药杂志

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

Preparation and evaluation of Indigo Naturalis dry suspension based on powder surface modification / 药学学报

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m2·g-1 and 12.512 m2·g-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.

Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients.@*METHODS@#The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro.@*RESULTS@#The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01).@*CONCLUSION@#The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

Chronic psychological stress aggravates intestinal barrier damage and promotes enteritis development through inhibiting Wnt/β-catenin pathway / 中华微生物学和免疫学杂志

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

Effect of cerebrotein hydrolysate-on intestinal microflora regulation of mice with Parkinson's disease / 解剖学报

Objective To investigate the neuroprotective effect and mechanism of cerebrotein hydrolysate- (CH-) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson's disease (PD) mice. Methods Totally 36 healthy male C57BL/6 mice were randomly divided into control group(Ctrl), model group(MPTP) and CH- group. MPTP was used to induce PD model in mice, and CH- was injected intraperitoneally for intervention. The behavioral function of mice was detected by pole test, the expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry, and the composition and diversity of intestinal microflora were detected by gene sequencing and bioinformatics analysis. Results Compared with the control group, MPTP induced behavioral deficits in PD mice after modeling (P<0.05), after CH- treatment, the behavioral defects of PD mice were improved compared with MPTP group (P<0.05). Immunohistochemical result showed that MPTP decreased the expression of the rate-limiting enzyme TH in dopamine synthesis, and increased the expression of TH after CH- treatment. The result of microbial diversity showed that the intestinal microflora diversity of mice decreased after MPTP treatment (P<0.05). At the “phylum” level, the number of Epsilonbacteraeota and Deferribacteres decreased sharply, while the number of Verrucomicrobia increased significantly. At the level of “family”, the number of Desulfovibrionaceae, Lachnospiraceae, Helicobacteraceae and Rikenellaceae decreased, while the number of Akkermansiaceae and Erysipelotrichaceae increased, suggesting that the original homeostasis of intestinal microflora was destroyed. After CH- treatment, the number of intestinal microflora tended to be normal, which reduced the abundance of pathogenic microbiota and increased the relative abundance of beneficial bacteria. Conclusion CH- can improve the composition of intestinal microflora and the behavioral function of PD mice by decreasing the abundance of pathogenic microbiota and increasing the relative abundance of beneficial bacteria.

Species and population density of malaria vector Anopheles in Sichuan Province from 2011 to 2021 / 中国血吸虫病防治杂志

Objective To investigate the distribution of malaria vector Anopheles in Sichuan Province from 2011 to 2021, so as to provide the scientific evidence for improving the surveillance of malaria vector Anopheles and preventing re-establishment of imported malaria in Sichuan Province. Methods The density and species of Anopheles mosquitoes were investigated using human-bait trapping and light trapping techniques in malaria vector surveillance sites of Sichuan Province from 2011 to 2021. The number, population and density of captured Anopheles mosquitoes were collected and descriptively analyzed, and the geographical distribution map of malaria vectors was plotted using the software ArcGIS 10.7 in Sichuan Province. Results A total of 152 243 Anopheles mosquitoes were captured in malaria vector surveillance sites of Sichuan Province from 2011 to 2021, including 150 987 An. sinensis (99.18%) and 1 256 An. anthropophagus (0.82%), and no other Anopheles species were captured. The annual densities of An. sinensis and An. anthropophagus were 0.64 to 1.27 mosquitoes/(person-hour) and 0 to 0.07 mosquitoes/(person-hour) by the human-bait trapping technique, and 6.46 to 26.50 mosquitoes/(light-night) and 0 to 0.82 mosquitoes/(light-night) by the light trapping technique in malaria vector surveillance sites of Sichuan Province from 2011 to 2021. A relatively higher density of An. anthropophagus was seen in Renshou County, Jianyang City, Weiyuan County and Mabian Yi Autonomous County [> 0.40 mosquitoes/(person-hour)] by the human-bait trapping technique, and in Cuiping District and Gaoxian County in Yibin City [> 1.00 mosquito/(light-night)] by the light trapping technique in Sichuan Province from 2011 to 2018, with no An. anthropophagus captured from 2019 to 2021, and a relatively higher density of An. sinensis was detected in Emeishan City, Lushan County, Luojiang District, Tongchuan District and Zhaohua District [> 4.00 mosquitoes/(person-hour)] by the human-bait trapping technique, and in Huili County, Yuexi County, Dechang County, Langzhong City, Pingchang County and Xuanhan County [> 40.00 mosquitoes/(light-night)] by the light trapping technique in Sichuan Province from 2011 to 2021. Conclusions Malaria vectors were still widespread in Sichuan Province from 2011 to 2021, and An. sinensis was the dominant species of malaria vectors. There is still a risk of local re-establishment of imported malaria in Sichuan Province, and it is needed to continue to improve the surveillance of imported malaria cases and malaria vectors.

Factors affecting pulmonary arterial pressure in response to high-altitude hypoxic stress / 生理学报

The alteration of pulmonary artery pressure is an important physiological indicator to reflect the organism's adaptation to acclimatization or the pathological injury in response to high-altitude hypoxic environment. The effects of hypoxic stress at different altitudes for different time on pulmonary artery pressure are different. There are many factors involved in the changes of pulmonary artery pressure, such as the contraction of pulmonary arterial smooth muscle, hemodynamic changes, abnormal regulation of vascular activity and abnormal changes of cardiopulmonary function. Understanding of the regulatory factors of pulmonary artery pressure in hypoxic environment is crucial in clarifying the relevant mechanisms of hypoxic adaptation, acclimatization, prevention, diagnosis, treatment and prognosis of acute and chronic high-altitude diseases. In recent years, great progress has been made in the study regarding the factors affecting pulmonary artery pressure in response to high-altitude hypoxic stress. In this review, we discuss the regulatory factors and intervention measures of pulmonary arterial hypertension induced by hypoxia from the aspects of hemodynamics of circulatory system, vasoactive state and changes of cardiopulmonary function.

Research progress on the effect of mitochondrial and endoplasmic reticulum stress caused by hypoxia during pregnancy on preeclampsia and intrauterine growth restriction / 生理学报

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.

Network Meta-analysis of acupuncture and moxibustion for allergic rhinitis / 中国针灸

OBJECTIVE@#To review the therapeutic effect of acupuncture and moxibustion on allergic rhinitis based on the network Meta-analysis.@*METHODS@#The randomized controlled trials of acupuncture and moxibustion for allergic rhinitis were retrieved from the databases, starting from the date of establishment to August 17, 2020, i.e. the PubMed, EMbase, Cochrane Library, CNKI, Wanfang and VIP. The traditional Meta-analysis and network Meta-analysis were performed by RevMan5.3 and GeMTC0.14.3.@*RESULTS@#A total of 50 RCTs were included, including 4260 patients, involving 5 kinds of acupuncture and moxibustion therapies, such as acupuncture, moxibustion, acupoint application, acupoint thread-embedding and auricular point therapy.①In term of total effective rate, acupuncture, moxibustion and acupoint thread-embedding were superior to western medication and auricular point therapy (@*CONCLUSION@#The therapeutic effect of acupuncture and moxibustion on allergic rhinitis is better than western medication, and acupoint thread-embedding has the best curative effect.

A case report of HLRCC syndrome combined Ⅳ inferior vena cava tumor thrombus / 中华泌尿外科杂志

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a rare hereditary disease and characterized by cutaneous leiomyoma, uterine leiomyoma and/or renal cell carcinoma, but rarely associated with vena cava embolism. We treated 1 case of HLRCC syndrome patients with inferior vena cava tumor emboli (Mayo grade Ⅳ), confirmed after genetic testing, the patient and her family refused further treatment. The patient died after two months of follow-up after discharge.

Analysis of laboratory re-examination results in Sichuan Provincial Malaria Diagnostic Reference Laboratory from 2014 to 2020 / 中国血吸虫病防治杂志

Objective To re-examine the diagnosis results of reported malaria cases in Sichuan Province from 2014 to 2020, so as to assess the malaria diagnostic capability of Sichuan Provincial Malaria Diagnostic Reference Laboratory. Methods The blood and blood smear samples from reported malaria cases were collected by Sichuan Provincial Malaria Diagnostic Reference Laboratory from 2014 to 2020, and subjected to re-examinations using microscopy and nested PCR assay. The re-examination results were compared. Results A total of 1 710 samples from reported malaria cases were re-examined by Sichuan Provincial Malaria Diagnostic Reference Laboratory from 2014 to 2020, and 1 634 samples were identified positive, with a positive coincidence rate of 95.56% (1 634/1 710) and a 92.29% (1 508/1 634) total coincidence rate of the Plasmodium species. The coincidence rates with P. falciparum, P. vivax, P. malariae and P. ovale were 99.48% (961/966), 97.07% (430/443), 83.05% (98/118) and 67.86% (19/28), respectively, and the coincidence rate was 91.81% (1 513/1 648) between microscopic and nested-PCR results. Conclusions The capability of microscopists remains weak at grassroot medical institutions in Sichuan Province. Further training is required among microscopists to improve the malaria surveillance capability in Sichuan Province during the post-elimination stage.

A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases

Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.

A Case of Human Hepatic Alveolar Echinococcosis Accompanied by Lung and Brain Metastases

Alveolar echinococcosis (AE) is considered as a fatal zoonosis caused by the larvae of Echinococcus multilocularis. The lungs and brain are the most common metastatic organs. We report a human case of hepatic alveolar echinococcosis accompanied by lung and brain metastasis. In particular, the patient had a history of tuberculosis and the lung lesions were easily misdiagnosed as lung abscesses. The lesions of liver and lung underwent radical resection and confirmed as alveolar echinococcosis by pathological examination. The patient had no surgical complications after operation and was discharged after symptomatic treatment. Unfortunately, the patient later developed multiple intracerebral AE metastases. We required the patient to take albendazole orally for life and follow up.

The ABCG2 mRNA Synthesized in vitro Promoted Uric Acid Excretion in Mice / 中国生物化学与分子生物学报

Hyperuricemia is a chronic metabolic disease caused by the accumulation of uric acid in the body caused by purine metabolism disorder. In recent years, the incidence of hyperuricemia has increased and the age of onset is showing a younger trend. Finding effective therapeutic targets and treatment methods is a hot spot of current research. The urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is mainly expressed in the kidney and promotes uric acid excretion. In this study, ABCG2 mRNA was synthesized in vitro and transfected into hyperuricemia model mice to observe its effect on mouse uric acid levels. Firstly, the DNA template of ABCG2 mRNA was chemically synthesized, and then transcribed into mRNA in vitro, followed by modification and transfection into mouse TCMK-1 renal tubular epithelial cells. Finally, the protein expression in the cells was detected by Western blot. The results showed that the amount of protein expression in TCMK-1 cells was positively correlated with the amount of transfected mRNA (P < 0. 01), indicating a successful transfection. In animal experiments, twenty-four SPF mice were randomly divided into four groups (n = 6): control group, hyperuricemia model group, benzbromarone group [20 mg/(kg•d)] and mRNA group [2 mg/(kg•3d)]. The mice have been modeled and treated for 28 days. During this period, the body weight and growth status of the mice were monitored daily. After the treatment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen and liver xanthine oxidase were analyzed. The results showed that compared with the model group of mice, mRNA treatment can significantly reduce the levels of serum uric acid (100. 38 ± 10. 94), blood urea nitrogen (6. 30 ± 1. 10), and serum creatinine (30. 86 ± 5. 78, P<0. 05 or P<0. 01). It can also increase the level of urine uric acid (617. 48 ± 50. 34, P<0. 05) in mice and promote the excretion of uric acid. But it has no significant effect on the activity of xanthine oxidase (26. 19 ± 2. 58) in the liver. The pathological changes of mice kidney were observed by HE staining. The results showed that compared with mice in the model group, pathological damages such as renal tubular cell edema and inflammatory cell infiltration in the mRNA treatment group were significantly improved. The relative expression of mRNA in mice kidney was detected by qRT-PCR, and the protein expression of ABCG2 in mice kidney was detected by immunohistochemistry and Western blot. The results showed that the relative expression of ABCG2 mRNA and its protein were significantly up-regulated in the kidney tissues of mice in the mRNA group (P < 0. 01), indicating that the transfection was successful in vivo. In conclusion, ABCG2 mRNA synthetized and modified in vitro can be successfully expressed in hyperuricemia mice and promote excretion of uric acid and other organic ions, as well as improvement of renal injury in mice. These results provide experimental basis for the clinical application of ABCG2 as a target for the treatment of hyperuricemia related diseases.

Investigation on reproductive characteristics of Polygonatum cyrtonema / 中国中药杂志

The study is aimed to investigate the reproductive biology characteristics of Polygonatum cyrtonema, especially including phenology, flower bud differentiation, flowering timing, floral traits, pollen vigor and stigma receptivity. The results showed that P. cyrtonema forms inflorescence before the leaves spread. In the wild, P. cyrtonema is mainly pollinated by insects such as bumblebees, with a seed setting rate of 65.12%. The seed setting rate of indoor single plant isolation or self-pollination enclosed by parchment paper bag is 0, indicating that it is self-incompatible. In Lin'an city, seedlings begin to emerge from mid-March to early April(the temperature is higher than 7.5 ℃), buds begin to emerge from the end of March to mid-April, and then undergo the full bloom stage from mid-to-late April, and the final flowering stage from the end of April to mid-May. The whole flowering period lasts 36 to 45 days. There are obvious differences in the phenology of different provenances. The flowers come into bloom from the base to the top along the aboveground main axis, which usually contain 4-22 inflorescences with(2-) 4-10(-21) flowers per inflorescence. The flowering pe-riod for a single plant is 26-38 days. The single flower lasts about 20-25 days from budding to opening and withers 2 days after pollination, and then the ovary will gradually expand. If unpollinated, it will continue to bloom for 3-5 days and then wither. Flower development period is significantly related to pollen vigor and stigma remittance. The pollen viability is the highest when the flower is fully opened with anthers gathering on the stigma, and the receptivity is the strongest when the stigma protrudes out of the perianth and secretes mucus. The fruits and seeds ripen in October, and proper shading can ensure the smooth development and maturity of the seeds. This study provides a basis for the hybrid breeding and seed production of P. cyrtonema.

Factors related to postoperative adjuvant therapy of locally advanced cervical cancer and building of a nomogram prediction model / 国际肿瘤学杂志

Objective:To explore the related factors of postoperative adjuvant therapy for cervical cancer stagedⅠB1-ⅡA2 [according to 2018 International Federation of Gynecology and Obstetrics (FIGO) staging standard], and to establish a nomogram model to predict the risk of postoperative adjuvant therapy for locally advanced cervical cancer.Methods:A total of 714 patients with cervical squamous cell cancer staged FIGO ⅠB1-ⅡA2 treated by surgery in Anhui Provincial Hospital were selected as the research objects from January 2009 to December 2019, and their clinicopathological data were analyzed. Multiple logistic regression analysis was used to determine the influencing factors, and a nomogram model was established to predict the risk of postoperative adjuvant treatment of cervical cancer. The predictive performance of the model was evaluated with the consistency index (C-index), and the compliance of the model was evaluated with the calibration curve.Results:Univariate analysis suggested that postoperative adjuvant therapy for cervical cancer was associated with gravidity ( χ2=11.506, P=0.001), underlying disease (hypertension or diabetes) ( χ2=7.668, P=0.006), squamous cell cancer antigen (SCC-AG) level ( χ2=19.392, P<0.001), imaging risk factors ( χ2=16.392, P<0.001), FIGO stage ( χ2=25.686, P<0.001), tumor size ( χ2=9.392, P=0.025) and surgical path ( χ2=16.590, P<0.001). Multivariate logistic regression analysis suggested that the number of pregnancy >2 times ( OR=1.951, 95% CI: 1.355-2.808, P<0.001), SCC-Ag ≥1.5 μg/L ( OR=2.021, 95% CI: 1.444-2.829, P<0.001), FIGO stage ⅠB3-ⅡA2 [ⅠB3 ( OR=1.933, 95% CI: 1.139-3.282, P=0.015); ⅡA1 ( OR=2.723, 95% CI: 1.556-4.765, P<0.001); ⅡA2 ( OR=3.159, 95% CI: 1.502-6.646, P=0.002)], with underlying disease (hypertension or diabetes) ( OR=1.867, 95% CI: 1.051-3.318, P=0.033), imaging risk factors ( OR=1.997, 95% CI: 1.127-3.537, P=0.018), without neoadjuvant therapy [preoperative neoadjuvant therapy for 1 cycle ( OR=0.402, 95% CI: 0.207-0.783, P=0.007)] and laparoscopic surgery ( OR=2.177, 95% CI: 1.524-3.112, P<0.001) were independent influencing factors for postoperative adjuvant treatment of cervical cancer. Based on the screened variables, the nomogram model to predict the risk of postoperative adjuvant treatment for cervical cancer has good predictive performance (C-index was 0.702) and compliance. Conclusion:The number of pregnancy >2 times, SCC-Ag ≥1.5 μg/L, FIGO stage ⅠB3-ⅡA2, with underlying disease (hypertension or diabetes), imaging risk factors, without neoadjuvant therapy, and laparoscopic surgery are independent influencing factors for postoperative adjuvant treatment of cervical cancer. A nomogram model has been constructed to predict the risk of postoperative adjuvant therapy for locally advanced cerrical cancer, and it can provide evidence for clinical treatment selection.

Relationship between dengue viral load and clinical characteristics / 预防医学

Objective@#To determine the relationship between dengue virus load and clinical characteristics, so as to provide basis for dengue fever prevention and treatment.@*Methods @#The dengue viral load and typing of 120 patients in Gongshu District of Hangzhou from June to November 2017 were detected by real-time fluorescent quantitative RT-PCR;the clinical indicators of these dengue patients were collected and their correlation with the viral load was analyzed.@*Results@#The DNA detection of dengue virus in 120 patients showed that they were all typeⅡ. The median dengue virus load was 3.91×104 copies/mL. All the patients had fever, the average peak temperature was（38.96 ± 0.69）℃. There were 102（85.00%）cases with asthenia;116（96.67%）cases with white blood cell count（WBC）less than 4× 109/L;119（99.17%）cases with platelet count（PLT）less than 100×109/L;114（95.00%）cases with glutamic oxaloacetate transaminase（GOT）more than 40 U/L;81（67.50%）cases with glutamic pyruvate transaminase（GPT）more than 52 U/L;58（48.33%）cases with creatine kinase（CK）more than 210 U/L. There was no significant correlation of dengue virus load with length of hospitalization, peak temperature,duration of fever, WBC,PLT, GOT, GPT and CK（P>0.05）. There were 75（62.50%）severe patients, and their median viral load was 9.29×104copies/mL, which was higher than 5.33×103copies/mL in non-severe patients（P<0.05）. @*Conclusion @#The dengue virus load is not related with length of hospitalization,peak temperature,WBC,PLT,GOT,GPT and CK,but with the severity of the disease.

Value of molecular genetics combined with bone marrow imaging detection in the prognosis judgement of acute myeloid leukemia with normal karyotype / 白血病·淋巴瘤

Objective To investigate the value of NPM1 and FLT3 gene mutation combined with bone marrow imaging detection in the prognosis judgement of initial treatment cytogenetically normal acute myeloid leukemia (CN-AML). Methods The clinical data of 100 patients (non-M3 type) with primary and initial treatment CN-AML from January 2010 to January 2014 in the Peace Hospital Affiliated of Changzhi Medical College were retrospectively analyzed. All patients were enrolled in the bone marrow imaging examination on the end day of induction treatment or the first day after the end of induction treatment (T time point). Univariate and multivariate prognostic analyses were performed on AML patients according to FLT3 and NPM1 gene status, bone marrow juvenile cell ratio at T time point. Results A total of 100 patients included 36 cases with FLT3 gene mutation and 44 cases with NPM1 gene mutation. The complete remission (CR) rate of CN-AML patients was 13.9% (5/36) and 71.9% (46/64), respectively (P< 0.01), 2-year recurrence-free survival (RFS) rate was 5.6% and 59.8%, respectively (P< 0.01), 2-year overall survival (OS) rate was 15.6% and 66.2%, respectively in FLT3+group and FLT3-group (P<0.01). The median RFS and median OS time in FLT3+ group was 6.9 months and 9.4 months, respectively, and the median RFS and median OS time in FLT3-group had not yet reached. There were no significant differences of all the indexes between the two groups (all P< 0.01). And there were no significant differences in CR rate, 2-year RFS rate and 2-year OS rate between NPM1+group and NPM1-group (all P＞0.05). The CR rate, 2-year RFS rate and 2-year OS rate in NPM1+ FLT3-group were better than those in NPM1- FLT3-, NPM1-FLT3+and NPM1+FLT3+groups; NPM1-FLT3+and NPM1+FLT3+groups had the worst prognosis, and there were no statistical differences in the CR rate, RFS and OS time between the two groups (all P＞ 0.05). The prognosis of the patients in bone marrow juvenile cell ratio < 0.05 group at T time point was better than that in ratio ≥0.05 group (all P< 0.05). CN-AML patients were classified into the good prognosis group (NPM1-FLT3-), the medium prognosis group (NPM1+FLT3-), and the poor prognosis group (NPM1-FLT3+and NPM1+FLT3+) according to the FLT3 and NPM1 genes. The good prognosis group+the ratio of bone marrow juvenile cells at T time point<0.05 group, the good prognosis group+the ratio of bone marrow juvenile cells at T time point≥0.05 group, the medium prognosis group + the ratio of bone marrow juvenile cells at T time point < 0.05 group had no statistical differences in CR rate, 2-year RFS rate and 2-year OS rate (all P ＞0.05). The medium prognosis group + the ratio of bone marrow juvenile cells at T time point ≥0.05 group, the poor prognosis group+the ratio of bone marrow juvenile cells at T time point<0.05 group had the equivalent prognosis, and the average prognosis was moderate; the poor prognosis group + the ratio of bone marrow juvenile cells at T time point ≥ 0.05 group had the worst prognosis. According to Cox multivariate regression analysis, FLT3 gene mutation and the ratio of bone marrow juvenile cells at T time point were independent influencing factors for RFS and OS in CN-AML patients (all P< 0.05). NPM1 was an independent prognosis factor affecting RFS and OS of FLT3-patients (all P < 0.05). Conclusions After induction chemotherapy, the responsiveness and sensitivity of AML patients to chemotherapy regimen can be assessed early and objectively according to molecular genetics and the ratio of bone marrow juvenile cells at T time point, which has a certain value in the prognosis judgement.

Hypoxia inducing factor related genetic adaptation in high-altitude and pharmacological modulation / 药学学报

Adaptation to hypoxia of the plateau environment has been a focus of scientific research in decades. The geographical distributions of such living environment include the Qinghai-Tibet Plateau, Andean Plateau in South America and Ethiopian Plateau. Over the past century, the unique features of physiological adaptation to high-altitude chronic hypoxia have been documented scientifically. The genetic studies of hypoxic adaptation in the past decade have revealed genetic bases of human high-altitude adaptation, with a close relationship to the hypoxia inducible factor (HIF) pathway and hypoxia response elements (HREs). Interestingly, the genetic pattern of adaptation to hypoxia is not the same among the three plateau populations. Tibetan has developed the best high-altitude adaptation, with modification of the HIF pathway as the key genetic element. Due to the wide range of HIF pathways, HIFs could regulate hundreds of downstream genes and are closely related to various diseases such as cancer, inflammation, ischemia, acute organ damage and infection, etc. The treatment researches of these diseases through HIFs-related regulations have led to the development of stabilizers and inhibitors of HIF pathway. We review here the adaptive responses of the three plateau populations to the hypoxic environment, and the genetic mechanism of HIF and HREs in the different ethnic high-altitude populations. Classes of HIF inhibitors, such as PI3K and/or mammalian target of rapamycin (mTOR) inhibitors, DNA-binding inhibitors, histone deacetylase inhibitors, heat-shock protein 90 inhibitors, cardiac glycosides, transcription inhibitors, topoisomerase inhibitors, and HIF activators including 2-OG mimics, Fe2+ chelators, prolyl hydroxylase (PHD) active-site blockers and CUL2 deneddylators have been presented with the drug examples. In addition, the top 3 chemical-disease and chemical-gene (protein) co-occurrences have been presented from the Pubmed literature search. The review could serve as references for research of hypoxia adaptation and HIF-related diseases.