COVID-19 vaccination affects short-term anti-coagulation levels in warfarin treatment.

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points. Logistic regression analysis was performed to determine covariates related to INR variations after COVID-19 vaccination. Vaccination safety was also monitored. There was a significant difference in INR values between INR0 and INR1 (2.15 vs. 2.26, p = 0.003), yet no marked difference was found between INR0 and INR2. The linear mixed effect model also demonstrated that INR variation was significant in short-term but not in medium-term or long-term period after vaccination. Logistic regression analysis showed that no investigated covariates, including age, vaccine dose, genetic polymorphisms of VKORC1 and CYP2C9 etc., were associated with short-term INR variations. Two patients (2.11%) reported gingival hemorrhage in the short-term due to increased INR values. The overall safety of COVID-19 vaccines for patients on warfarin was satisfying. COVID-19 vaccines may significantly influence warfarin anticoagulation levels 3-5 days after vaccination. We recommend patients on warfarin to perform at least one INR monitoring within the first week after COVID-19 vaccination.

Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

The contradictory roles of tightly bound and loosely bound extracellular polymeric substances of activated sludge in trimethoprim adsorption process.

Extracellular polymeric substances (EPS) of activated sludge are a mixture of high molecular weight polymers secreted by microorganisms, which have the double structure of tightly-bound EPS (TB-EPS) in inner layer and loosely-bound EPS (LB-EPS) in outer layer. The characteristic of LB- and TB-EPS were different, which would affect their adsorption of antibiotics. However, the adsorption process of antibiotics on LB- and TB-EPS was still unclear yet. Therefore, in this work, the roles of LB-EPS and TB-EPS in adsorption of a typical antibiotic-trimethoprim (TMP) at environmentally relevant concentration (25.0 µg/L) were investigated. The results showed the content of TB-EPS was higher than that of LB-EPS, which was 17.08 and 10.36 mg/g VSS, respectively. The adsorption capacity of raw, LB-EPS extracted and both LB- and TB-EPS extracted activated sludges for TMP were 5.31, 4.65 and 9.51 µg/g VSS, respectively, which indicated LB-EPS had positive effect on TMP removal, while TB-EPS had negative effect. The adsorption process can be well described by a pseudo-second-order kinetic model (R2 > 0.980). The ratio of different functional groups was calculated and the CO and C-O bond might be responsible for the adsorption capacity difference between LB- and TB-EPS. The fluorescence quenching results indicated that tryptophan protein-like substances in LB-EPS provided more binding sites (n = 0.36) than that of tryptophan amino acid in TB-EPS (n = 0.1). Furthermore, the extend DLVO results also demonstrated that LB-EPS promoted the adsorption of TMP, while TB-EPS inhibited the process. We hope the results of this study were helpful for understanding the fate of antibiotics in wastewater treatment systems.

Human poliovirus receptor contributes to biliary atresia pathogenesis by exacerbating natural-killer-cell-mediated bile duct injury.

BACKGROUND AND AIMS: Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK-cell modulator. Here, we explored the role of PVR in BA pathogenesis. METHODS: Poliovirus receptor expression and NK cell-associated genes were detected in human BA samples and a rotavirus-induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK-cell-mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high-mobility group box 1 (HMGB1), and interleukin-1beta (IL-1beta) levels were measured in a cohort of 50 patients using ELISA. RESULTS: Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus-induced BA. Activation of the TLR3-IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell-mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL-1beta levels. CONCLUSIONS: Poliovirus receptor contributes to BA pathogenesis by regulating NK cell-mediated bile duct injury; PVR has the value as a biomarker of BA.

New monoamine antidepressant, hypidone hydrochloride (YL-0919), enhances the excitability of medial prefrontal cortex in mice via a neural disinhibition mechanism.

Hypidone hydrochloride (YL-0919) is a novel antidepressant in clinical phase II trial. Previous studies show that YL-0919 is a selective 5-HT (serotonin) reuptake inhibitor, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist, which exerts antidepressant effects in various animal models, but its effects on neural function remain unclear. Medial prefrontal cortex (mPFC), a highly evolved brain region, controls highest order cognitive functions and emotion regulation. In this study we investigated the effects of YL-0919 on the mPFC function, including the changes in neuronal activities using electrophysiological recordings. Extracellular recording (in vivo) showed that chronic administration of YL-0919 significantly increased the spontaneous discharges of mPFC neurons. In mouse mPFC slices, whole-cell recording revealed that perfusion of YL-0919 significantly increased the frequency of sEPSCs, but decreased the frequency of sIPSCs. Then we conducted whole-cell recording in mPFC slices of GAD67-GFP transgenic mice, and demonstrated that YL-0919 significantly inhibited the excitability of GABAergic neurons. In contrast, it did not alter the excitability of pyramidal neurons in mPFC slices of normal mice. Moreover, the inhibition of GABAergic neurons by YL-0919 was prevented by pre-treatment with 5-HT1A receptor antagonist WAY 100635. Finally, chronic administration of YL-0919 significantly increased the phosphorylation levels of mTOR and GSK-3ß in the mPFC as compared with vehicle. Taken together, our results demonstrate that YL-0919 enhances the excitability of mPFC via a disinhibition mechanism to fulfill its rapid antidepressant neural mechanism, which was accomplished by 5-HT1A receptor-mediated inhibition of inhibitory GABAergic interneurons.

Critical role of PAFR/YAP1 positive feedback loop in cardiac fibrosis.

Aberrant activation of cardiac fibroblasts is the main cause and character of cardiac fibrosis, and inhibition of cardiac fibrosis becomes a promising treatment for cardiac diseases. Platelet-activating factor (PAF) and Hippo pathway is recently recognized as key signaling mechanisms in cardiovascular diseases. In this study we explored the potential roles of PAF and Hippo signaling pathway in cardiac fibrosis. Myocardial infarction (MI) was induced in mice by left anterior descending artery ligation. After 28 days, the mice were sacrificed, and the hearts were collected for analyses. We showed that PAF receptor (PAFR) and yes-associated protein 1 (YAP1, a key effector in the Hippo pathway) were significantly increased in the heart of MI mice. Increased expression of PAFR and YAP1 was also observed in angiotensin II (Ang II)-treated mouse cardiac fibroblasts. In mouse cardiac fibroblasts, forced expression of YAP1 increased cell viability, resulted in collagen deposition and promoted fibroblast-myofibroblast transition. We showed that PAF induced fibrogenesis through activation of YAP1 and promoted its nuclear translocation via interacting with PAFR, while YAP1 promoted the expression of PAFR by binding to and activating transcription factor TEAD1. More importantly, silencing PAFR or YAP1 by shRNA, or using transgenic mice to induce the conditional deletion of YAP1 in cardiac fibroblasts, impeded cardiac fibrosis and improved cardiac function in MI mice. Taken together, this study elucidates the role and mechanisms of PAFR/YAP1 positive feedback loop in cardiac fibrosis, suggesting a potential role of this pathway as novel therapeutic targets in cardiac fibrosis.

Mzb1 protects against myocardial infarction injury in mice via modulating mitochondrial function and alleviating inflammation.

Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle dilation and cardiac dysfunction, eventually developing into heart failure. Mzb1 (Marginal zone B and B1 cell specific protein 1) is a B-cell-specific and endoplasmic reticulum-localized protein. Mzb1 is an inflammation-associated factor that participates a series of inflammatory processes, including chronic periodontitis and several cancers. In this study we investigated the role of Mzb1 in experimental models of MI. MI was induced in mice by ligation of the left descending anterior coronary artery, and in neonatal mouse ventricular cardiomyocytes (NMVCs) by H2O2 treatment in vitro. We showed that Mzb1 expression was markedly reduced in the border zone of the infarct myocardium of MI mice and in H2O2-treated NMVCs. In H2O2-treated cardiomyocytes, knockdown of Mzb1 decreased mitochondrial membrane potential, impaired mitochondrial function and promoted apoptosis. On contrary, overexpression of Mzb1 improved mitochondrial membrane potential, ATP levels and mitochondrial oxygen consumption rate (OCR), and inhibited apoptosis. Direct injection of lentiviral vector carrying Len-Mzb1 into the myocardial tissue significantly improved cardiac function and alleviated apoptosis in MI mice. We showed that Mzb1 overexpression significantly decreased the levels of Bax/Bcl-2 and cytochrome c and improved mitochondrial function in MI mice via activating the AMPK-PGC1α pathway. In addition, we demonstrated that Mzb1 recruited the macrophages and alleviated inflammation in MI mice. We conclude that Mzb1 is a crucial regulator of cardiomyocytes after MI by improving mitochondrial function and reducing inflammatory signaling pathways, implying a promising therapeutic target in ischemic cardiomyopathy.

RGD-hirudin-based low molecular weight peptide prevents blood coagulation via subcutaneous injection.

Thromboembolic disease is a common cardio-cerebral vascular disease that threatens human life and health. Thrombin not only affects the exogenous coagulation pathway, but also the endogenous pathway. Thus, it becomes one of the most important targets of anticoagulant drugs. RGD-hirudin is an anticoagulant drug targeting thrombin, but it can only be administered intravenously. We designed a low molecular weight peptide based on RGD-hirudin that could prevent blood clots. We first used NMR to identify the key amino acid residues of RGD-hirudin that interacted with thrombin. Then, we designed a novel direct thrombin inhibitor peptide (DTIP) based on the structure and function of RGD-hirudin using homology modeling. Molecular docking showed that the targeting and binding of DTIP with thrombin were similar to those of RGD-hirudin, suggesting DTIP interacted directly with thrombin. The active amino acids of DTIP were identified by alanine scanning, and mutants were successfully constructed. In blood clotting time tests in vitro, we found that aPTT, PT, and TT in the rat plasma added with DTIP were greatly prolonged than in that added with the mutants. Subcutaneous injection of DTIP in rats also could significantly prolong the clotting time. Thrombelastography analysis revealed that DTIP significantly delayed blood coagulation. Bio-layer interferometry study showed that there were no significant differences between DTIP and the mutants in thrombin affinity constants, suggesting that it might bind to other sites of thrombin rather than to its active center. Our results demonstrate that DTIP with low molecular weight can prevent thrombosis via subcutaneous injection.

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update.

BACKGROUND/AIMS: Current practical advances in high-throughput data technologies including RNA-sequencing have led to the identification of long non-coding RNAs (lncRNAs) for potential clinical application against bladder urothelial cancer (BLCA). However, most previous studies focused on the clinical value of individual lncRNAs, which has limited the potential for future clinical application. METHODS: In this study, RNA-sequencing data of lncRNAs was downloaded from The Cancer Genome Atlas database. Risk score was constructed based on survival-associated lncRNAs identified using differential expression analysis as well as univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic and Kaplan-Meier curve analyses were employed to evaluate the clinical and prognostic value of risk scores. Bioinformatics analyses were used to investigate the potential mechanisms of newly identified lncRNAs. RESULTS: Among 2,127 differentially expressed lncRNAs (DELs), four new lncRNAs (AC145124.1, AC010168.2, MIR200CHG, and AC098613.1) showed valuable prognostic effects in BLCA patients. More importantly, the four-DEL-based risk score had the potential to become an independent marker for the survival status prediction of BLCA patients. Distinct co-expressed genes and signaling pathways were identified when BLCA was categorized into low- and high-risk groups. Furthermore, a protein-coding gene, HIST4H4 was found only 68 bp from the AC010168.2 DEL. HIST4H4 expression level was evidently up-regulated and positively correlated with AC010168.2 in BLCA patients. CONCLUSION: This in silico investigation pioneers the future investigation of the utility of prognostic lncRNAs for BLCA.

Efficacy of artemether and artesunate in mice infected with praziquantel non-susceptible isolate of Schistosoma japonicum.

Praziquantel is currently the only drug of choice for the treatment of human Schistosoma japonicum infections, and praziquantel-based chemotherapy has been proved to be generally effective to control the morbidity and reduce the prevalence and intensity of S. japonicum infections. However, the potential emergence of praziquantel resistance in S. japonicum seriously threatens the elimination of this neglected tropical disease in China. The purpose of this study was designed, in mouse animals, to evaluate the in vivo efficacy of artemether and artesunate against praziquantel non-susceptible S. japonicum. Mice infected with a praziquantel non-susceptible isolate and a praziquantel-susceptible isolate of S. japonicum were treated with artemether and artesunate at a single oral dose of 300 mg/kg given once on each of days 7-8 and 35-36 post-infection to assess the efficacy against juvenile and adult worms. Administration with artemether and artesunate at a single oral dose of 300 mg/kg on each of days 7-8 post-infection resulted in total worm burden reductions of 72.8 and 73.5% in mice infected with praziquantel-susceptible S. japonicum, and 77.9 and 74.1% in mice infected with the non-susceptible isolate (both P values >0.05), while the same treatments given on days 35-36 post-infection reduced total worm burdens by 71.4 and 69.6% in mice infected with the susceptible isolate, and 75.3 and 69.6% in mice infected with the non-susceptible parasite (both P values >0.05). It is concluded that there is no evidence for reduced susceptibility of artemether and artesunate in praziquantel non-susceptible S. japonicum.

Soil characteristics and heavy metal accumulation by native plants in a Mn mining area of Guangxi, South China.

Revegetation and ecological restoration of a Mn mineland are important concerns in southern China. To determine the major constraints for revegetation and select suitable plants for phytorestoration, pedological and botanical characteristics of a Mn mine in Guangxi, southern China were investigated. All the soils were characterized by low pH and low nitrogen and phosphorus levels except for the control soil, suggesting that soil acidity and poor nutrition were disadvantageous to plant growth. In general, the studied mine soils had normal organic matter (OM) and cation exchange capacity (CEC). However, OM (8.9 g/kg) and CEC (7.15 cmol/kg) were very low in the soils from tailing dumps. The sandy texture and nutrient deficiency made it difficult to establish vegetation on tailing dumps. Mn and Cd concentrations in all soils and Cr and Zn concentrations in three soils exceeded the pollution threshold. Soil Mn and Cd were above phytotoxic levels, indicating that they were considered to be the major constraints for phytorestoration. A botanical survey of the mineland showed that 13 plant species grew on the mineland without obvious toxicity symptoms. High Mn and Cd concentrations have been found in the aerial parts of Polygonum pubescens, Celosia argentea, Camellia oleifera, and Solanum nigrum, which would be interesting for soil phytoremediation. Miscanthus floridulus, Erigeron acer, Eleusina indica, and Kummerowia striata showed high resistance to the heavy metal and harsh condition of the soils. These species could be well suited to restore local degraded land in a phytostabilization strategy.

ITFG2, an immune-modulatory protein, targets ATP 5b to maintain mitochondrial function in myocardial infarction.

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.

A case report and literature review on primary solitary fibrous tumor of the bladder.

RATIONALE: Solitary fibrous tumors (SFT) is a rare mesenchymal tumor originating from a CD34-positive dendritic mesenchymal cell, most of which is benign, the most common sites is pleura and mediastinum, and rarely in the bladder. The clinical manifestations are mainly related to the tumor volume. When the tumor volume is large, it will compress the surrounding tissues or organs and cause corresponding symptoms. Laparoscopic Incision biopsy is effective means for diagnosing SFT. PATIENT CONCERNS: A 70-year-old female patient was admitted to the hospital with a bladder neoplasm detected by computed tomography scan after experiencing intestinal obstruction 3 days following esophageal cancer surgery. She denied any history of tumor disease. DIAGNOSES: No abnormality was found in the physical examination and laboratory testing after admission. Ultrasound imaging showed a large solid mass with low echogenicity in the bladder. Urological computed tomography with 3D reconstruction revealed a large cystic-solid mass located on the right wall of the bladder, measuring approximately 6.8 cm × 7.1 cm × 6.5 cm, with uneven density and mild inhomogeneous enhancement after contrast administration. Cystoscopy revealed a large mucosal bulge on the right wall of the bladder and laparoscopic exploration revealed a smooth-surfaced round mass, approximately 7 cm in size. INTERVENTIONS: Incision biopsy was performed to make a clear diagnosis, and appropriate tissue specimens were obtained for pathological testing. OUTCOMES: The patient was diagnosed as SFT according to pathology. The patient was followed up for 6 months after surgery, and no recurrence was observed. LESSONS: SFT occurring in the bladder are extremely rare, and the site is scarcely reported in the relevant literature; thus, it is easy to misdiagnose and laparoscopic incision biopsy may be a good choice.

Tendon microstructural disruption promotes tendon-derived stem cells to express chondrogenic genes by activating endoplasmic reticulum stress.

The erroneous differentiation of tendon-derived stem cells (TDSCs) into adipocytes, chondrocytes, and osteoblasts is believed to play an important role in the development of tendinopathy. However, the regulatory mechanisms of TDSC differentiation remain unclear. The aim of this study is to investigate the contribution and mechanism of the tendon microstructural disruption to the differentiation of TDSCs. Bovine Achilles tendons were sliced. The tendon slices were stretched with different tensile strains to mimic the tendon structure alteration at various scales. The TDSCs were cultured on the tendon slices. The differentiation of TDSCs and endoplasmic reticulum (ER) stress in the TDSCs were investigated with quantitative reverse transcription polymerase chain reaction, immunostaining and western blot. The effect of ER stress inhibition on chondrogenic differentiation of the TDSCs was further investigated. The structural alteration did not affect the viability of TDSCs. However, the structural alteration of tendon slices with 6.4% strain promoted TDSCs to express the chondrogenic genes. ER stress-related markers, ATF-4 and PERK, were also upregulated. With the inhibition of ER stress, the expression of ATF-4 and the chondrogenic gene SOX9 of TDSCs were inhibited. The study indicated that tendon microdamage could induce the chondrogenic differentiation of TDSCs through triggering ER stress to activate ATF-4 and SOX9 subsequently.

Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease: a cohort study.

BACKGROUND: The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention. METHODS: The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis. RESULTS: The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome. CONCLUSIONS: ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.

[Effects of Nitrogen Speciation Transformation on Microbial Community Succession in Input Rivers of Miyun Reservoir].

The Miyun Reservoir is the major source of surface drinking water in Beijing. However, the total nitrogen (TN) concentrations in the Miyun Reservoir and inflowing rivers have recently been increasing. In this study, the Mangniu River, a typical inflow river in the upper reaches of the Miyun Reservoir, was selected as the study area to investigate the spatial distribution and transformation of various nitrogen forms from the perspective of microbial community composition and predicting function, aimimg at providing a scientific reference for nitrogen pollution control of the Miyun Reservoir. The results indicated that except for TN, all the other physical and chemical water quality indicators in the upper reaches of the Miyun Reservoir met the Class II criteria of the environmental quality standards for surface water in China (GB 3838-2002). Additionally, NO3--N was the primary constituent of TN, ranging from 77.7% to 92.9%. Banchengzi Reservoir has a certain self-purification ability because its high C/N ratio promotes denitrification. Significant differences in microbial community structure were observed between the water and sediments of Mangniu River along with spatial distribution. High NO3--N concentration was the major environmental factor affecting the succession of microbial community structure. Many nitrification and denitrification microorganisms existed in Mengniu River, and the relative abundance of denitrification bacteria (DNB) was higher than that of nitrification bacteria, and that in the sediments was slightly higher than that in the water. Nitrosopumilus and Pseudomonas were the dominant nitrification and denitrification bacteria in Mengniuhe River, respectively. The results of phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt2) showed that NO3--N reduction module was the major nitrogen metabolism module, which primarily occurred in water. The abundance of the functional genes for nitrification (i.e., narGH) was the highest in water, and the major functional gene involved in NO3--N reduction was nirBD of DNRA, which was primarily present in the sediments; however, the main functional gene involved in denitrification was nirK.

The safety and feasibility of laparoscopic approach for the management of intrahepatic and extrahepatic bile duct stones in patients with prior biliary tract surgical interventions.

The purpose of this study was to compare the efficacy and safety of laparoscopic and open reoperation for intrahepatic and extrahepatic bile duct stones patients with previous biliary tract surgical procedures. The clinical data were retrospectively analyzed of intrahepatic and extrahepatic bile duct stones patients with previous biliary tract surgical procedures who underwent reoperation in the Second General Surgery Department of China Medical University from January 2012 to February 2018. 44 eligible cases were selected. In accordance with the surgical procedures, they were divided into a laparoscopy group (n = 23) and an open surgery group (n = 21). No statistically significant differences were found in the preoperative general clinical data between the two group. Two patients in the laparoscopy group were converted to open surgery. Comparisons between the two groups showed that the intraoperative blood loss [90.87 ± 62.95 (ml) vs. 152.38 ± 118.82 (ml)], the proportion of postoperative analgesia [10/23 (43.5%) vs. 16/21 (76.2%)], and the length of stay [7.19 ± 5.32 (d) vs. 11.00 ± 4.66 (d)] in the laparoscopy group were significantly lower than those in the open surgery group (P < 0.05). Laparoscopic biliary reoperation for intrahepatic and extrahepatic bile duct stones was feasible. Compared with open surgery, laparoscopic surgery has the advantages of less bleeding, a shorter postoperative length of stay, and a lower rate of additional postoperative analgesia.

Effects of different courses of moxibustion treatment on intestinal flora and inflammation of a rat model of knee osteoarthritis.

OBJECTIVE: This study was done to determine the effects of different courses of moxibustion on a rat knee osteoarthritis (KOA) model, and explore the dose-effect relationship of moxibustion on KOA from the perspectives of intestinal flora and inflammatory factors. METHODS: Wistar rats were randomly divided into five groups: normal, model, moxibustion for 2 weeks, moxibustion for 4 weeks and moxibustion for 6 weeks groups (n = 5 each group). A KOA rat model was induced by monosodium iodoacetate, and moxibustion intervention was performed at the acupoints "Dubi" (ST35) and "Zusanli" (ST36), once every other day. Pathologic changes in the cartilage of rat knee joints were assessed after intervention, and fecal samples were subjected to 16S rRNA high-throughput sequencing for microbial diversity analysis. RESULTS: Damage to the knee articular cartilage was obvious in the model group, which also had increased levels of pro-inflammatory factors, decreased levels of anti-inflammatory factors, and intestinal flora disorders with decreased diversity. The degree of cartilage damage in the 4 and 6 weeks of moxibustion groups was significantly improved compared with the model group. The 4 and 6 weeks of moxibustion groups also demonstrated reduced levels of interleukin-1ß and tumor necrosis factor-α and increased levels of interleukin-10 (P < 0.05). Both the abundance and diversity of the intestinal flora were increased, approaching those of the normal group. Abundances of probiotics Eubacterium coprostanoligenes group and Ruminococcaceae UCG-014 increased, while that of the pathogenic bacteria Lachnospiraceae NK4A136 group decreased (P < 0.05). Although the abundance of Lachnospiraceae NK4A136 group decreased in the 2 weeks of moxibustion group compared with the model group (P < 0.05), there was no statistically significant difference in serum inflammatory factors, flora species diversity or degree of pathological damage compared with the model group. CONCLUSION: Moxibustion treatment led to significant improvements in the intestinal flora and inflammatory factors of rats with KOA. Moxibustion treatment of 4 and 6 weeks led to better outcomes than the 2-week course. Moxibustion for 4 and 6 weeks can regulate intestinal flora dysfunction with increased probiotics and reduced pathogenic bacteria, reduce pro-inflammatory factors and increase anti-inflammatory factors. No significant differences were seen between the effects of moxibustion for 4 weeks and 6 weeks.

Fluorescence-based method for fast quantification of active aluminums in natural and treated water.

Fast quantitative determination of active aluminum (Ala) in natural and treated water is extremely desirable. The fluorescence method based on complexation by 8-hydroxyquinoline (8-HQ) is highly promising, but the measurement could be severely interfered by hardness ions and natural organic matter (NOM). This study was devoted to refining the 8-HQ complexation-fluorescence method for measurement of Ala by eliminating the interferences. Results showed that magnesium ions at a typical concentration in natural water could have a substantial positive interference, due to the formation of Mg-8-HQ complexes which have fluorescence regions similar to Al-8-HQ. NOM, represented by fulvic acid (FA), could not interfere the aluminum measurement considerably. It was primarily because 8-HQ has much stronger complexing ability than NOM with aluminum. Theoretical calculations showed that reducing the buffering pH (from 7.5) to 6.5 or using a masking ligand such as edetate (EDTA) could effectively alleviate the interference mainly caused by magnesium. Experimental results confirmed the theoretical predictions. Refined procedures were suggested for more accurate while fast determination of Ala in natural or treated water. The refined method has a quantification limit of ~4 µg/L, a linear range of measurement up to 700 µg/L, and a relative standard deviation of ~0.8%.

[Effect of moxibustion on quality of life in tumor patients: network Meta-analysis].

OBJECTIVE: To rank the effectiveness of various moxibustion methods on the quality of life in tumor patients, and explore the best treatment plan of moxibustion for improving the quality of life in tumor patients from the perspective of evidence-based medicine. METHODS: The Chinese and English literature of randomized controlled trial (RCT) of the effect of moxibustion on the quality of life in tumor patients were searched in PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang and VIP. The retrieval time was from the establishment of the databases to October 31, 2020. The R3.6.2 and Stata15.0 software were used for network Meta-analysis based on Bayesian model. RESULTS: A total of 30 Chinese RCTs were included, including 2 169 patients, involving 16 interventions. In terms of the effectiveness of improving quality of life, the top three treatments were special moxibustion plus other therapies 1 (either of tendon acupuncture, acupoint pressing, acupoint injection, etc.), wheat-grain moxibustion and mild moxibustion. The special moxibustion methods were the combination of fire-dragon moxibustion, thunder-fire moxibustion, fuyang fire moxibustion and moxa salt-bag moxibustion. The number of literature of these four moxibustion methods was small. Considering the clinical application of moxibustion, it was concluded that wheat-grain moxibustion ranked first. CONCLUSION: The adjuvant treatment of wheat-grain moxibustion is more effective than other moxibustion methods on improving the quality of life in tumor patients, but the results needed to be further verified because the bias risk of RCT included in this study is high and the sample size is small.