Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Penicillium marneffei infection after renal transplantation: one case report / 中华器官移植杂志

Clinical data were retrospectively reviewed for one case of penicillium marneffei infection after renal transplantation (RT) to explore a proper management of peniciliosis marneffei (PSM)transplantation.This case had a history of pulmonary tuberculosis and underwent RT due to uremia.After discharging, postoperative recovery was excellent.Recurrent cough occurred at Month 7 post-operation.Fiberoptic bronchoscopy and pulmonary CT indicated a possibility of pulmonary tuberculosis.However, a definite diagnosis of PSM was confirmed by next generation sequencing (NGS) and pathogenic bacteria culture of alveolar lavage fluid.After adjusting immunosuppressive agents and regular antifungal treatment with voriconazole, respiratory symptoms improved and pulmonary CT hinted at a resorption of lesion.Features of pulmonary CT and bronchoscopic examination were nearly similar to those of tuberculosis.Thus early bacterium culture and NGS may aid an definite diagnosis.Voriconazole is an effective treatment of the disease.

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.@*METHODS@#Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined.@*RESULTS@#Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05).@*CONCLUSION@#CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

Correlation between progesterone receptor G1978T polymorphism and endometrial cancer / 中国临床药理学与治疗学

To explore the relationship between progesterone receptor (PGR) gene G1978T polymorphism and endometrial carcinoma. METHODS: After searching PubMed, EMBASE, Wan-fang and CNKI databases for literatures on PGR G1978T genotyping of endometrial cancer patients, the data were extracted and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using STATA15. The whole blood samples of endometrial carcinoma cases (EC group) and normal women (control group) were collected. Allelic-specific primers matching G1978T wild type G allele and mutant type T allele were designed with 3' terminal phosphorothioate modification, and the two-directional primer extension was performed using Exo + polymerase to genotype PGR gene G1978T polymorphism and Sanger sequencing was used to verify the genotype. RESULTS: PGR gene G1978T mutation was marginally associated with endometrial carcinoma risk (ORper allele =1.10, 95%CI=0.98-1.24, P= 0.072). At the same time, only 1 normal blood samples were found with PGR gene G1978T mutation, and the differences in genotypes and allele frequency between the case group and the control group were not statistically significantP>0.05. CONCLUSION: The G1978T polymorphism of the PGR gene maybe not be associated with the risk of endometrial carcinoma.

Epidemiology, pathogenesis, and management of Coronavirus disease 2019-associated stroke / 医学前沿

The Coronavirus disease 2019 (COVID-19) epidemic has triggered a huge impact on healthcare, socioeconomics, and other aspects of the world over the past three years. An increasing number of studies have identified a complex relationship between COVID-19 and stroke, although active measures are being implemented to prevent disease transmission. Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality, posing a serious challenge to acute stroke diagnosis, treatment, and care. This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke, including arterial stroke (ischemic stroke and hemorrhagic stroke) and venous stroke (cerebral venous thrombosis). Additionally, the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented. Evidence on vaccinations, potential therapeutic approaches, and effective strategies for stroke management has been highlighted.

Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study / 中华医学杂志(英文版)

BACKGROUND@#Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.@*METHODS@#Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.@*RESULTS@#Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.@*CONCLUSION@#Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.@*CLINICAL TRIAL REGISTRATION@#Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Involvement of Interleukin-1 β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.@*METHODS@#Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively.@*RESULTS@#After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01).@*CONCLUSION@#EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway.

Clinical evaluation of antral septal maxillary sinus floor elevation by the disk-up sinus reamer / 中华口腔医学杂志

Objective: To investigate the clinical effect of disk-up sinus reamer (DSR) in maxillary sinus floor elevation with maxillary sinus septum. Methods: Twenty-four patients were included between January 2019 to January 2020 in Department of Oral Implantology, The Affiliated Hospital of Qingdao University. There were 10 males and 14 females with the age of (39.3±11.7) years old (range 22-56 years). Pre-operative(T0) cone-beam CT (CBCT) was taken for measurement and analysis. All patients were divided into group E (easy situations, septum located anterior to the zygo-matic process), group M (moderate situations, septum located pos-terior to the zygo-matic process) and group D (difficult situations, sagittally oriented septum). The maxillary sinus floor was grafted through the crestal approach by DSR and implants were placed simultaneously. Permanent repair was performed 6-8 months after operation. All patients underwent CBCT before surgery, after surgery immediately (T1), 6 months after surgery(T2), 1 year after surgery(T3), 2 year after surgery(T4). The residual bone height (RBH) and the vertical bone height (VBH) were analyzed. The mucosal perforation rate, implant survival rate were counted. Results: All the 24 patients completed the Maxillary sinus lift surgery successfully and 24 implants were placed simultaneously. All patients had no headache, dizziness. The mucosal perforation rate was 0. The survival rate of implants during the healing period was 100%(24/24). The RBH was (5.81±2.56) mm pre-operation, the VBHT1, VBHT2, VBHT3 and VBHT4 were (11.82±1.09), (10.98±0.52), (10.66±0.44) and (10.40±0.33) mm, respectively. The differences between the groups by pairing test were statistically significant (F=187.70, P0.001), expect VBHT3 and VBHT4 (P=0.071). Bone resorption and remodeling mainly occurred 1 year after surgery. One patient developed peri-implantitis 18 months after surgery. Conclusions: With the RBH of implant site>2 mm and existence of maxillary sinus septum, using DSR for sinus floor elevation has a high success rate. It can obtain enough bone height and complete the simultaneous implantation to form a good osseointegration. The DSR is simple, safe and controllable, and can shorten the operation time.

Microwave sensor for recognition of abnormal nodule tissue on body surface / 生物医学工程学杂志

For the detection and identification of abnormal nodular tissues on the body surface, a microwave sensor structure loaded with a spiral resonator is proposed in this paper, a sensor simulation model is established using HFSS software, the structural parameters are optimized, and the actual sensor is fabricated. The S21 parameters of the tissue were obtained when nodules appeared by simulation, and the characteristic relationship between the difference of S21 parameters with position was analyzed and tested experimentally. The results showed that when nodules were present in normal tissues, the curve of S21 parameter difference with position change had obvious inverted bimodal characteristics, and the extreme value of S21 parameter difference appeared when the sensor was directly above the nodules, which was easy to identify the position of nodules. It provides an objective detection tool for the identification of abnormal nodular tissues on the body surface.

Interferon-related gene array in predicting the efficacy of interferon therapy in chronic hepatitis B / 生物医学工程学杂志

This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT 2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children / 中华儿科杂志

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells / 中华肿瘤杂志

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

One-year follow-up results of atrial fibrillation patients who undergoing transcatheter aortic valve implantation / 中华心血管病杂志

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.

Effect of tumor necrosis factor-α overexpress on the biological properties dental pulp stem cells in microoxidative stress / 解剖学报

Objective To investigate the effect of tumor necrosis factor-α(TNF-α) on biological properties of dental pulp stem cells (DPSCs) in low-oxidation stress. Methods The experimental groups were as follows: normox, normox control plasmid, normox-TNF-α, 3% O

Metabolic engineering of yeasts for green and sustainable production of bioactive ginsenosides F2 and 3β,20S-Di-O-Glc-DM

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS).@*METHODS@#Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular.@*RESULTS@#Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group.@*CONCLUSION@#EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

The glycosyltransferases involved in triterpenoid saponin biosynthesis: a review / 生物工程学报

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.

SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.@*METHODS@#A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.

Comparison of the efficacy of anti-vascular endothelial growth factor drugs with or without retinal laser photocoagulation for macular edema secondary to retinal vein occlusion: a systematic review / 中华眼底病杂志

Objective:To evaluate the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs combined with retinal laser photocoagulation and anti-VEGF drugs alone in the treatment of retinal vein occlusion (RVO) combined with macular edema (ME).Methods:A evidence-based medicine study. Retinal vein occlusion (obstruction), macular edema, anti-vascular endothelial growth factor, bevacizumab, ranibizumab, conbercept, aflibercept, and retinal laser photocoagulation were the Chinese and English search terms. Related literature was searched in China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Embase, Cochrane Library. RVO combined with ME was selected as the research object, and the treatment plan was a clinical randomized controlled study comparing intravitreal injection of anti-VEGF drugs combined with laser photocoagulation and anti-VEGF drugs alone. The search time range was from January 2011 to February 2021. Repeated, incomplete or irrelevant literature, case reports and review literature were excluded. Review Manager 5.4 statistical software was used to conduct a meta-analysis of the literature. The weighted mean difference (WMD) and 95% confidence interval ( CI) were selected as the estimated value of effect size, and the fixed effect model was used for analysis. The evaluation indicators were best corrected visual acuity (BCVA), center macular thickness (CMT), and the number of injections. Results:According to the search strategy, 461 articles were initially retrieved, and 21 articles were finally included for meta-analysis. A total of 1156 patients were enrolled, of which 576 were treated with anti-VEGF drugs combined with laser photocoagulation (combined treatment group), and 580 were treated with anti-VEGF drugs alone (drug treatment group). Meta-analysis results showed that there was no statistically significant difference in BCVA and CMT between the drug treatment group and the combination treatment group at 6, 9, and 12 months after treatment (BCVA: WMD =-0.82, 95% CI -2.38-0.74, P=0.30; CMT: WMD=-3.12, 95% CI -17.25-11.01, P=0.67). For patients with branch retinal vein occlusion and ME, combined therapy can reduce the number of injections more effectively than drug therapy alone ( WMD=-0.80, 95% CI -1.18--0.42, Z=4.10, P <0.000 1). Conclusion:Compared with pure intravitreal injection of anti-VEGF drugs, combined retinal laser photocoagulation can not better improve BCVA and CMT in patients with RVO and ME. For patients with branch retinal vein occlusion and ME, combined retinal laser photocoagulation can effectively reduce the resistance. The number of VEGF injections.

Human parvovirus B19 infection-associated anemia after liver transplantation: three case reports with a literature review / 中华器官移植杂志

Objective:To explore the diagnosis and treatment of pure red cell aplastic anemia (PRCA) caused by parvovirus B19 (HPV-B19)infection after liver transplantation (LT).Methods:Three adult PRCA patients caused by parvovirus B19 infection after LT were reviewed retrospectively.The relevant literatures were collected to sort out the detection methods and treatment of parvovirus B19 infection after LT.Results:All three patients received liver transplantation due to end-stage liver disease with massive intraoperative blood transfusion and smooth postoperative recovery.Severe anemia occurred at 1-2 Months after discharge.Hemorrhagic anemia was excluded after re-admission and PRCA was diagnosed by bone marrow aspiration and next generation sequencing (NGS). After tapering the intensity of immunosuppressive therapy, intravenous immunoglobulin (IVIG) was administered for 7-10 days and hemoglobin soon normalized.A review of 15 recent literatures on HPV-B19 infection after LT revealed that the diagnosis and treatment of parvovirus B19 infection after LT gradually were became same.Conclusions:HPV-B19 infection causes PRCA after LT in adults.Diagnosing with NGS, intravenous injection of immunoglobulin and modification of immunosuppressant regimen may achieve excellent therapeutic efficacies.