Objective To explore the effect of proprioceptive neuromuscular facilitation (PNF) on balance function of stroke patients in community. Methods 204 stroke patients in community were divided into control group (n=98) and observation group (n=106). The control group accepted routine rehabilitation and the observation group received PNF additionally. Fugl-Meyer Assessment of lower extremities (FMA), Berg Balance Scale (BBS) and static balance locator were used to evaluate the motor and balance function before and 3 months after treatment. Results The scores of FMA and BBS were higher after treatment than before (P<0.05) in both groups, and were higher in observation group than in control group (P<0.05). The length of path (L), covered area (A) and L/A were less in observation than in control group (P<0.05) both in the eye-open and eye-closed modes. Conclusion PNF can improve the lower extremities motor and balance function of stroke patients in community.

Objective To investigate the application of colostomy care products in managing the leakage around PTCD drainage tube, and to discuss its clinical effect. Methods A total of 56 patients with malignant obstructive jaundice, who had received PTCD and suffered from postoperative leakage around PTCD drainage tube, were randomly and equally divided into the study group (n=28) and the control group (n=28). The colostomy care powder, the skin protective film and the colostomy bag were used for the patients of the study group, while iodophors, sterile gauze and mupirocin ointment were employed for the patients of the control group. The incidence of irritant dermatitis around PTCD drainage tube, the degree of comfort to the indwelling tube judged by the patient, and the nursing workload for PTCD drainage tube were determined, and the results were compared between the two groups. Results The incidence of irritant dermatitis around PTCD drainage tube in the study group was obviously lower than that in the control group. And the degree of comfort to the indwelling tube judged by the patient in the study group was much higher than that in the control group. The differences between the two groups were statistically significant (P<0.05). Conclusion Combination use of colostomy care powder, skin protective film and colostomy bag can effectively reduce the incidence of irritant dermatitis around PTCD drainage tube and improve the patient’s condition. Therefore, this method is worthy of popularization in clinical practice.

Bombyx mori bidensovirus (BmBDV) has been identified as causing chronic densonucleosis in Bombyx mori specifically. The replication mechanism of BmBDV remains unknown. Its genome comprises two single stands DNA (VD1 and VD2). In order to rescue infectious virions in vitro, we obtained the total viral DNA extracted from the BmBDV-infected larvae midguts, subsequently cloned the full-length sequence of BmBDV genome fragments by PCR and constructed recombinant plasmids pMD18T-VD1 and pUC-VD2. The linear genome fragments were obtained by digesting recombinant plasmids with corresponding restriction enzymes, and then collectively transfected BmN cells by the method of liposome-embedding. We determined the replication of the virus gene by PCR with the template of demethylated total DNA extracted from the post-transfect BmN cells. Meanwhile, we collected the total proteins from the post-transfect BmN cells and the larvae midgut of feeding the post-transfect BmN cells to perform Western blotting analysis, and detected the expression of viral genes. Here we firstly confirm that infectious virions can be rescued in BmN cells by linear co-transfect method.
Animals ; Bombyx ; DNA, Viral ; Densovirus ; growth & development ; Larva ; Transfection ; Virion ; Virus Cultivation

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Background and Objectives: p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis. Methods: and Results: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34＋ cells, but it significantly decreased the production of CD43＋ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis. Conclusions In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43＋ cells, but not CD34＋ cells. The mechanisms via which CD34＋ cells are blocked by RUNX1b overexpression remain to be elucidated.

Tetracycline (TC) natural products possess a variety of remarkable bioactivities and diverse structures. They are an important and fertile source for developing novel drugs. As one of the most successful drug families, TC antibiotics have been in clinical use for over seven decades, and continue to make an important contribution to human health nowadays. To date, studies on TC natural products and their biosynthesis have revealed numerous novel biochemical mechanisms and regulatory elements, which facilitates the rational metabolic engineering studies for generating novel bioactive TC analogs and inspires the development of new synthetic biology tools. In this review, we provide a comprehensive overview on the discovery, biosynthesis, and engineering of the existing TC natural products. These analyses will be of great value for the discovery, design and development of novel TC drugs in the future.
Humans ; Biological Products/metabolism* ; Anti-Bacterial Agents ; Metabolic Engineering ; Synthetic Biology ; Tetracycline

OBJECTIVE: To develop a mortality prediction model for critically ill patients based on multidimensional and dynamic clinical data collected by the hospital information system (HIS) using random forest algorithm, and to compare the prediction efficiency of the model with acute physiology and chronic health evaluation II (APACHE II) model. METHODS: The clinical data of 10 925 critically ill patients aged over 14 years old admitted to the Third Xiangya Hospital of Central South University from January 2014 to June 2020 were extracted from the HIS system, and APACHE II scores of the critically ill patients were extracted. Expected mortality of patients was calculated according to the death risk calculation formula of APACHE II scoring system. A total of 689 samples with APACHE II score records were used as the test set, and the other 10 236 samples were used to establish the random forest model, of which 10% (n = 1 024) were randomly selected as the validation set and 90% (n = 9 212) were selected as the training set. According to the time series of 3 days before the end of critical illness, the clinical characteristics of patients such as general information, vital signs data, biochemical test results and intravenous drug doses were selected to develope a random forest model for predicting the mortality of critically ill patients. Using the APACHE II model as a reference, receiver operator characteristic curve (ROC curve) was drawn, and the discrimination performance of the model was evaluated through the area under the ROC curve (AUROC). According to the precision and recall, Precision-Recall curve (PR curve) was drawn, and the calibration performance of the model was evaluated through the area under the PR curve (AUPRC). Calibration curve was drawn, and the consistency between the predicted event occurrence probability of the model and the actual occurrence probability was evaluated through the calibration index Brier score. RESULTS: Among the 10 925 patients, there were 7 797 males (71.4%) and 3 128 females (28.6%). The average age was (58.9±16.3) years old. The median length of hospital stay was 12 (7, 20) days. Most patients (n = 8 538, 78.2%) were admitted to intensive care unit (ICU), and the median length of ICU stay was 66 (13, 151) hours. The hospitalized mortality was 19.0% (2 077/10 925). Compared with the survival group (n = 8 848), the patients in the death group (n = 2 077) were older (years old: 60.1±16.5 vs. 58.5±16.4, P < 0.01), the ratio of ICU admission was higher [82.8% (1 719/2 077) vs. 77.1% (6 819/8 848), P < 0.01], and the proportion of patients with hypertension, diabetes and stroke history was also higher [44.7% (928/2 077) vs. 36.3% (3 212/8 848), 20.0% (415/2 077) vs. 16.9% (1 495/8 848), 15.5% (322/2 077) vs. 10.0% (885/8 848), all P < 0.01]. In the test set data, the prediction value of random forest model for the risk of death during hospitalization of critically ill patients was greater than that of APACHE II model, which showed by that the AUROC and AUPRC of random forest model were higher than those of APACHE II model [AUROC: 0.856 (95% confidence interval was 0.812-0.896) vs. 0.783 (95% confidence interval was 0.737-0.826), AUPRC: 0.650 (95% confidence interval was 0.604-0.762) vs. 0.524 (95% confidence interval was 0.439-0.609)], and Brier score was lower than that of APACHE II model [0.104 (95% confidence interval was 0.085-0.113) vs. 0.124 (95% confidence interval was 0.107-0.141)]. CONCLUSIONS The random forest model based on multidimensional dynamic characteristics has great application value in predicting hospital mortality risk for critically ill patients, and it is superior to the traditional APACHE II scoring system.
Female ; Male ; Humans ; Aged ; Adult ; Middle Aged ; Adolescent ; Critical Illness ; Hospitalization ; Length of Stay ; APACHE ; Hospital Information Systems

OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools， i.e. JPKD， SmartDose and NextDose， in predicting tacrolimus dose and blood concentration after kidney transplantation， and analyze the influential factors of prediction accuracy. METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected. Three individualized dosing tools， i.e. JPKD， SmartDose and NextDose， were used to predict the dose and plasma concentration of tacrolimus. The absolute prediction error （APE） and prediction error （PE） between the measured value and the predicted value， and prediction success rate were calculated （APE＜30% indicating a good forecast）. Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage， as well as the predicted and measured blood concentration values using three software； univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD， SmartDose and NextDose. RESULTS A total of 110 hospitalized patients were included in this study， and tacrolimus doses and plasma concentrations were monitored. The predicted doses of JPKD， SmartDose and NextDose were （2.0±0.7）， （2.7±1.9）， （1.8±0.8） mg， their measured value was （1.9±0.6） mg， and the correlation coefficients between the predicted values and the measured value were 0.841， 0.450， 0.247 （P＜0.001）； the median APEs were 6.00%， 52.07% and 30.40%， and the median PEs were 5.00%， 18.50% and －3.50%； the prediction success rates were 98.45%， 30.05% and 49.22%. The predicted values of tacrolimus concentrations using JPKD， SmartDose， NextDose were （6.74±3.36）， （6.93±5.02）， 9.00（5.80±12.60） ng/mL， the measured value was 8.64（7.11，9.77） ng/mL， and the correlation coefficients between the predicted values and the measured value were 0.997 （P＜0.001）， －0.066 （P＝0.360）， 0.920 （P＜0.001）. The median APEs were 5.54%， 45.91% and 35.56%， and PEs were －4.94% （median）， －17.050% （median） and 36.93% （average value）； the prediction success rates were 97.93%， 32.64% and 37.31%. Univariate analysis showed that the dosage， blood concentration， body weight， transplantation time and others were related to the prediction accuracy （P＜0.05）. CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools， from high to low， are JPKD， NextDose， and SmartDose， suggesting that JPKD can be prioritized in clinical use.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.
Aged ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occult Blood