Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.

ObjectiveTo investigate related factors for severe acute pancreatitis (SAP) with sepsis. MethodsA retrospective analysis was performed for the clinical data of 178 SAP patients who were admitted from January 2007 to March 2020, and according to the presence or absence of sepsis, they were divided into sepsis group with 56 patients and non-sepsis group with 122 patients. The t-test was used for comparison of continuous data between the two groups, and the chi-square test was used for comparison of categorical data between the two groups. A logistic regression model was used for multivariate analyses. ResultsThe incidence rate of sepsis was 31.46% in SAP patients. The univariate analysis showed that there were significant differences between the patients without sepsis and those with sepsis in APACHEⅡ score, blood glucose, blood calcium, serum total cholesterol, serum triglyceride, blood urea nitrogen, serum creatinine, serum albumin, admission to the intensive care unit, hypoxemia, deep venous catheterization, mechanical ventilation, surgical procedure, blood purification, indwelling urinary catheterization, and extent of pancreatic necrosis (all P＜0.05). The multivariate analysis showed that APACHEⅡ score (odds ratio ［OR］=6.748, 95% confidence interval ［CI］: 2.191-20.788, P＜0.05), hypoxemia (OR=3.383, 95% CI: 1.112-10.293, P＜0.05), blood glucose (OR=5.288, 95%CI: 1.176-23.781, P＜0.05), extent of pancreatic necrosis (OR=5.523, 95%CI: 1.575-19.360, P＜0.05), and serum creatinine (OR=5.012, 95%CI: 1.345-18.762, P＜0.05) were independent risk factors for infectious SAP with sepsis, while laparoscopic removal of focal necrotic tissue (OR=0.250, 95%CI: 0.066-0951, P＜0.05) was an independent protective factor against SAP with sepsis. ConclusionThere are several important measures to reduce SAP with sepsis, including blood glucose control, protection of the functions of important organs such as lungs and kidneys, application of minimally invasive surgery to remove focal necrotic tissue, and emphasis on the treatment of critically ill patients with a high degree of pancreatic necrosis.

Objective:To investigate the clinical application value of blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) to the protection of language function in patients with unilateral frontal and temporal lobes glioma receiving postoperative intensity modulation radiation therapy (IMRT).Methods:A total of 27 patients with unilateral frontal and temporal lobe gliomas were treated with postoperative radiotherapy. The planning CT and BOLD-fMRI were performed before radiotherapy, and the language functional areas were delineated based on the fused images of 3D T1 and CT. IMRT technology was used to develop radiotherapy plans with and without language function area protection, naming conventional and protective radiotherapy plans respectively. The maximum radiation dose ( Dmax), average radiation dose ( Dmean), target conformal (CI) and dose uniformity (HI) of PTV of the two plans were compared and analyzed to ensure that the protective radiotherapy plan could meet the radiotherapy standard. Then, the Dmax and Dmean of the language function area were compared and analyzed to evaluate whether the Dmax and Dmean of the language function area were decreased in the protective radiotherapy plan. Results:There were no significant differences in CI, HI, Dmax and Dmean of PTV between the conventional radiotherapy plan and protective radiotherapy plan ( P>0.05). There were statistically significant differences in Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) between the conventional radiotherapy plan and protective radiotherapy plan ( t=3.073-12.707, P<0.05). Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) were decreased in the protective radiotherapy plan compared with the conventional radiotherapy plan, and the decrease was significant in the healthy side. Conclusions:BOLD-fMRI combined with IMRT can not only guarantee the target dose of patients with glioma receiving postoperative radiotherapy, but also reduces the radiation dose to the language function area. Chinese reading task and paragraph comprehension task are the stimulation mode of language function in patients after brain tumor surgery. These tasks are simple and the effect is accurate.

Objective:To study the factors related to infection by multiple drug-resistant bacteria (MDROs) in patients with infectious pancreatic necrosis (IPN).Methods:A retrospective study was conducted on the clinical data of 134 IPN patients with definitive etiologies treated in the Department of General Surgery, the Third Affiliated Hospital of Guizhou Medical University from January 2009 to February 2020. There were 85 males and 49 females. The age was (46.69±14.11) years. The IPN patients were divided into the multiple and the non-multiple MDROs infection groups based on drug resistance of pathogens in drainage fluid. The difference between the two groups of patients, including the number of antibacterial drugs used, the number of combined antibacterial drugs, the length of ICU stay, and other related factors were analyzed. Univariate and multivariate analyses were performed.Results:Among the 134 patients with IPN, 41 (30.60%) had complex MDROs infection and 93 (69.40%) had non complex MDROs infection. Univariate analysis showed that the course of disease, APACHE II score, extrapancreatic infection, number of surgical operations, time from onset to operation, patency of drainage tube, length of ICU stay, time of using antibiotics, number of changing courses of antibiotics, number of combined antibiotics, blood glucose and glycosylated hemoglobin were related to occurrence of multiple MDROs (all P<0.05); Multivariate analysis showed that glycated hemoglobin ( OR=3.957, 95% CI: 1.073-14.600), time from onset to operation ( OR=6.086, 95% CI: 1.263-29.325), number of changing courses of antibiotics ( OR=3.560, 95% CI: 1.077-11.772), number of combined antibiotics ( OR=3.560, 95% CI: 1.077-11.772), length of ICU stay ( OR=3.590, 95% CI: 1.126-11.448) were independent risk factors of MDROs infection in IPN patients ( P<0.05). Conclusion:Early debridement of infective foci, good control of blood glucose, reduced length of ICU stay, rational use of antibiotics to avoid unnecessary changing courses of antibiotics, appropriate use of combination of antibiotics could reduce the number of MDROs infection in IPN patients.

Objective:To explore the correlation of cognitive impairment with abnormal brain regions having low-frequency fluctuation (ALFF) by resting-state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with mild hepatic encephalopathy (MHE).Methods:Fifty-nine patients (28 patients with chronic cirrhosis and 31 patients with MHE, according to results of digital symbol test [DST] scores/digital connection test A [NCT-A] scores) admitted to our hospital from March 2018 to January 2020 were enrolled; 33 healthy control subjects matched in gender, age and years of education were chosen as controls. Resting-state BOLD-fMRI was performed in all subjects, and the original images were processed to obtain ALFF brain map. Statistical methods were used to obtain the brain regions with different ALFF values in the three groups, and the brain regions enjoying correlations between ALFF values and venous blood ammonia content/DST scores/NCFA scores in patients from the MHE group.Results:As compared with the control group, patients in the MHE group exhibited significantly lower ALFF values in the right central posterior gyrus, bilateral cuneiform lobe, left lateral occipital gyrus, left occipital gyrus, and left pars opercularis, and significantly increased ALFF values in the right thalamus, left parahippocampal gyrus and surrounding ventricle (bilateral caudate nucleus head)( P<0.05). Bivariate correlation analysis suggested that ALFF values were negatively correlated with blood ammonia in the left pars opercularis, left margin superior gyrus, bilateral precuneus, left superior temporal gyrus, right middle frontal gyrus and surrounding area, and right insula ( P<0.05); ALFF values were positively correlated with DST scores in left medial cingulate gyrus and right cerebellar hemisphere; ALFF values in the left frontal lobe and left posterior cerebellar lobe were positively correlated with NCT-A scores, and ALFF values in the left parahippocampal gyrus were negatively correlated with NCT-A scores ( P<0.05). Conclusion:The ALFF differences in multiple brain regions of patients with MHE may be related to cognitive impairment.

Agricultural activities, including stock-farming, planting industry, and fish aquaculture, can affect the physicochemical and biological characters of freshwater lakes. However, the effects of pollution producing by agricultural activities on microbial ecosystem of lakes remain unclear. Hence, in this work, we selected Honghu Lake as a typical lake that is influenced by agriculture activities. We collected water and sediment samples from 18 sites, which span a wide range of areas from impacted and less-impacted areas. We performed a geospatial analysis on the composition of microbial communities associated with physicochemical properties and antibiotic pollution of samples. The co-occurrence networks of water and sediment were also built and analyzed. Our results showed that the microbial communities of impacted and less-impacted samples of water were largely driven by the concentrations of TN, TP, NO-N, and NO-N, while those of sediment were affected by the concentrations of Sed-OM and Sed-TN. Antibiotics have also played important roles in shaping these microbial communities: the concentrations of oxytetracycline and tetracycline clearly reflected the variance in taxonomic diversity and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Furthermore, for samples from both water and sediment, large differences of network topology structures between impacted and less-impacted were also observed. Our results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu Lake.
Agriculture ; Animals ; Anti-Bacterial Agents ; analysis ; China ; Eutrophication ; Geologic Sediments ; chemistry ; microbiology ; Lakes ; chemistry ; microbiology ; Microbiota ; Risk Factors ; Water Pollutants, Chemical ; analysis

Objective To analyze the magnetic resonance imaging (MRI) images of patients with adult Japanese encephalitis (JE),and to investigate the diagnostic value of MRI for the disease.Methods Thirty-two adult JE patients who underwent cranial MRI at General Hospital of Ningxia Medical University between August 2016 and September 2018 were enrolled.All patients had disease onset between August and September and they aged 17 to 83 years old.The clinical data,laboratory results,MRI signal characteristics of each scanning sequence and the distribution of the brain lesions were retrospectively analyzed.Results Of the 32 adult JE patients,29 (90.6％)cases had acute onset,28 (87.5％) cases had unconsciousness and cognitive impairment,26 (81.2％) cases had intracranial hypertension,3 (9.4％) cases had meningeal irritation,3 (9.4％) cases had Parkinson-like symptoms,10 (31.2％) cases had epilepsy,and 15 (46.9％) cases had decreased muscle strength.Twenty patients were positive for JE virus-specific IgM antibodies.Twenty-eight patients underwent cerebrospinal fluid examination,15 (53.6％) cases showed intracranial pressure ≥180 mmH2O (1 mmH2O =0.009 8 kPa),7 (25％) cases developed lymphocyte reaction,and 16 (57.1％) cases showed mixed cell reaction.Twenty-three cases (71.9％) showed lesions of brain on MRI,including thalamus (17 cases,73.9％),hippocampus (13 cases,56.5％),cerebral peduncle (6 cases,26.1％),cortical and subcortical (4 cases,17.4％),basal ganglia (2 cases,8.7％),brainstem (1 case,4.3％) and splenium of corpus callosum (1 case,4.3％).Positive T1 weight image (T1WI) and T2 weight image (T2WI) results were found in 21 patients,respectively,23 patients had positive T2-fluid attenuated inversion recovery (FLAIR) images,and 20 patients had positive diffusion weighted imaging (DWI) images.Among them,T2-FLAIR and DWI images showed more lesions,wider range of lesions and clearer boundary of cortical involvement range than T1WI and T2WI images.Conclusions Bilateral thalamus and hippocampus are often involved in adult JE.T2-FLAIR and DWI sequences are more sensitive to detect lesions.Combining MRI images with epidemiological characteristics,clinical manifestations,and laboratory tests is of great assistance for early diagnosis of JE.

Objective To explore the application effect of growth hormone in patients ≥35 years old with diminished ovarian reserve (DOR),and to analyze pregnancy outcome.Methods A total of 120 cases with diminished ovarian reserve (≥35 years old) in our hospital were randomly divided into observation group and control group,each group of 60 cases.The control group was given conventional treatment,while the observation group added growth hormone.Changes of follicle stimulatng homone (FSH) and luteinizing hormone (LH),FSH/LH,serum estradiol (E2) level were compared between the two groups before and after treatment,along with the pregnancy outcome of two groups such as normal fertilization rate,excellent embryo rate,quantity of egg,cleavage rate,cycle cancellation rate.Results After treatment,the FSH and FSH/LH of the observation group were significantly lower than those of the control group,the serum E2 was significantly higher than that of the control group (P ＜ 0.05);the normal fertilization rate,cleavage rate and excellent embryo rate in the observation group were 53.96％,86.67％ and 35.38％ respectively,which were significantly higher than those of 33.58％,71.11％ and 15.63％ in the control group (P ＜ 0.05);the cycle cancellation rate of the observation group was 6.67％,which was significantly lower than that of 21.67％ in the control group (P ＜ 0.05);the biochemical pregnancy rate and clinical pregnancy rate of the observation group were 38.33％ and 28.33％,which were significantly higher than those of 20％ and 13.33％ in the control group (P ＜ O.05).Conclusions Diminished ovarian reserve in patients ≥35 years old with growth hormone therapy,can promote the improvement of ovarian function,the biochemical pregnancy rate and clinical pregnancy rate,it is worthy of clinical promotion.

Objective Based on Chinese guidelines for the management of ischemic stroke, a standardized stroke management program was performed to provide intensive education and training for medical physicians, aiming to enhance their knowledge and ability for ischemic stroke prevention and treatment, thereby reducing patients′ in-hospital cost and length of stay, and improving patients′ clinical prognosis. Methods This study was conducted in 20 general hospitals throughout Hainan province. A total of 163 physicians from 20 hospitals involved in the management of stroke patients were trained by highly experienced physicians based on the Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2014 and the Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack 2014. Prior to and post the standardized stroke management training, the data of 3218 and 3367 patients with ischemic stroke were respectively collected. Quality of life assessments including the Barthel index (BI) and the modified Rankin Scale (mRS) score of all patients were recorded at baseline and after discharge. The length of stay and in-hospital cost were directly collected from the hospital information system. Results Physicians′ knowledge and ability manifested as testing scores were significantly improved after training (78.2 ± 15.5 vs 55.6 ± 10.7, t=69.1, P<0.01). The average length of stay of post-training patients was significantly shorter than that of pre-training patients ((8.7 ± 0.9) vs (11.7 ± 1.5) days, t=97.9, P<0.01). The average in-hospital cost of post-training patients was significantly less than that of pre-training patients ((7681.7 ± 1397.7) vs (11846.2 ± 2514.6) Yuan, t=82.5, P<0.01). Both BI (68.2 ± 3.2 vs 43.5 ± 5.3, t=227.7, P<0.01) and mRS score (2.74±0.51 vs 3.65±0.71, t=59.5, P<0.01) were significantly improved for post-training patients. Multivariate linear regression analysis illustrated that standardized stroke management was negatively associated with in-hospital cost (r=-0.461, P<0.01), length of stay (r=-0.357, P<0.01) and mRS score (r=-0.298, P<0.01), and was positively associated with levels of BI (r=0.376, P<0.01). Conclusion Standardized stroke management program might be a cost-effective choice for the management of ischemic stroke as it reduces the in-hospital cost and improves patients′BI and mRS levels.