Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

Versatile Peptide-Based Nanosystems for Photodynamic Therapy.

Photodynamic therapy (PDT) has become an important therapeutic strategy because it is highly controllable, effective, and does not cause drug resistance. Moreover, precise delivery of photosensitizers to tumor lesions can greatly reduce the amount of drug administered and optimize therapeutic outcomes. As alternatives to protein antibodies, peptides have been applied as useful targeting ligands for targeted biomedical imaging, drug delivery and PDT. In addition, other functionalities of peptides such as stimuli responsiveness, self-assembly, and therapeutic activity can be integrated with photosensitizers to yield versatile peptide-based nanosystems for PDT. In this article, we start with a brief introduction to PDT and peptide-based nanosystems, followed by more detailed descriptions about the structure, property, and architecture of peptides as background information. Finally, the most recent advances in peptide-based nanosystems for PDT are emphasized and summarized according to the functionalities of peptide in the system to reveal the design and development principle in different therapeutic circumstances. We hope this review could provide useful insights and valuable reference for the development of peptide-based nanosystems for PDT.

Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis.

PURPOSE: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. METHODS: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. RESULTS: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. CONCLUSION: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

Relationship between complications of type 2 diabetes and thyroid nodules.

OBJECTIVE: Recent evidence suggests that diabetes is a risk factor for thyroid nodules. However, the relationship between complications of type 2 diabetes and the risk of thyroid nodules remains unclear. This present study aims to investigate the association between thyroid nodules and complications of type 2 diabetes. METHODS: This retrospective study collected 4696 adult inpatients with type 2 diabetes between January 2021 and December 2021. The complications examined in this paper included diabetic nephropathy, peripheral neuropathy, eye disorder, and peripheral vascular disease. RESULTS: A total of 4696 patients with type 2 diabetes participated in the study, of whom 19.6% had thyroid nodules. Among all the complications, eye disorder had the highest incidence of thyroid nodules (incidence rate, 29.4%; 95% CI, 26.23%-32.51%). The prevalence of thyroid nodules was lower among patients without complications (incidence rate, 14.1%; 95% CI, 12.48% -15.67%) compared to patients who had complications (incidence rate, 23.1%; 95% CI, 21.59%-24.68%) (p < 0.001). Logistic regression revealed that peripheral neuropathy (adjusted OR, 1.6; 95% CI, 1.4-1.9), eye disorder (adjusted OR, 1.8; 95% CI, 1.5-2.2), and peripheral vascular disease (adjusted OR, 1.8; 95% CI, 1.6-2.1) were all significantly associated with an increased risk of thyroid nodules. However, no significant correlation was found between diabetic nephropathy and the risk of thyroid nodules. CONCLUSION: One of the key findings of this study is that type 2 diabetes without complications is negatively correlated with the risk of thyroid nodules, while several complications are associated with a significantly increased risk of thyroid nodules.

Roles and regulatory mechanisms of KIN17 in cancers (Review).

KIN17, which is known as a DNA and RNA binding protein, is highly expressed in numerous types of human cancers and was discovered to participate in several vital cell behaviors, including DNA replication, damage repair, regulation of cell cycle and RNA processing. Furthermore, KIN17 is associated with cancer cell proliferation, migration, invasion and cell cycle regulation by regulating pathways including the p38 MAPK, NF-κB-Snail and TGF-ß/Smad2 signaling pathways. In addition, knockdown of KIN17 was found to enhance the sensitivity of tumor cells to chemotherapeutic agents. Immunohistochemical analysis revealed that there were significant differences in the expression of KIN17 between cancer tissues and adjacent tissues. Both the Kaplan-Meier survival analysis and multivariate Cox regression analysis indicated that KIN17 is aberrantly high expressed in various tumor tissues and is also associated with poor prognosis in patients with various tumor types. Taken together, KIN17 has key roles in tumorigenesis and cancer development. Investigating the relationship between KIN17 and neoplasms will provide a vital theoretical basis for KIN17 to serve as a diagnostic and prognostic biomarker for cancer patients and as a potential target for cancer therapy.

Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice.

Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor model in both Balb/c nude mice (xenograft), C57BL/6J mice (allograft), and hematogenous metastatic neoplasm in nude mice. NR (400 mg/kg bw) was supplied daily in gavage. In-situ tumor growth or noninvasive bioluminescence were measured to evaluate the effect of NR on the HCC process. HepG2 cells were treated with transforming growth factor-ß (TGF-ß) in the absence/presence of NR in vitro. We found that NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice in both subcutaneous xenograft and hematogenous metastasis models. NR supplementation decreased metastasis to the bone and liver in the hematogenous metastasis model. NR supplementation also significantly decreased the size of allografted tumors and extended the survival time in C57BL/6J mice. In vitro experiments showed that NR intervention inhibited the migration and invasion of HepG2 cells triggered by TGF-ß. In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of HCC progression.

In vitro antioxidant analysis of flavonoids extracted from Artemisia argyi stem and their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophages.

In this study, flavonoids were successfully extracted from Artemisia argyi stem, and their yield reached 15.3 mg/g dry A. argyi stem. The flavonoid extract from A. argyi stem had a purity of 88.58 % (w/w), meanwhile, which also contained 1.57 % (w/w) carbohydrates, 2.04 % (w/w) proteins and 7.81 % (w/w) polyphenols, respectively. In vitro antioxidant activity analysis showed the increased scavenging effects of flavonoid extract from A. argyi stem on 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-di-(3-ethyl-benzothiazolin-6-sulfonic acid) diammonium salt, hydroxyl, and superoxide radicals in a concentration-dependent manner. Furthermore, the flavonoid extract from A. argyi stem exerted protective effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting the levels of tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and nitric oxide free radicals. Overall, this work will provide guidance and help in the utilization of edible A. argyi as plant-based diet and its bioactive flavonoid extract as antioxidant and anti-inflammatory ingredients to improve the function, nutrition, and healthiness of foods.

KIN17 promotes cell migration and invasion through stimulating the TGF-ß/Smad2 pathway in hepatocellular carcinoma.

KIN17 DNA and RNA binding protein (Kin17) is involved in the regulation of tumorigenesis of diverse human cancers. However, its role in the cancer progression and metastasis in hepatocellular carcinoma (HCC) remains largely unknown. Bioinformatics and immunohistochemistry staining were used to investigate the expression pattern of KIN17 and its prognostic value in HCC patients. The transwell, wound-healing assay was employed to determine the effects of KIN17 on migration and invasion of HCC cells in vitro. The tail veins model was employed to determine the effects of KIN17 on lung metastasis in vivo. The biological mechanisms involved in cell migration and invasion regulated by KIN17 were determined with Western blot analysis method. KIN17 expression was significantly increased in HCC tissues compared with adjacent normal tissues, with particularly higher in portal vein tumor thrombus and intrahepatic metastasis tissues. Patients with higher KIN17 expression experienced poor overall and disease free survival. KIN17 knockdown in HuH7 and HepG2 cells significantly reduced cell migration and invasion abilities, whereas its overexpression promoted migration and invasion in MHCC-97L and HepG2 cells in vitro and in vivo. In HuH7 and HepG2 cells, KIN17 knockdown inhibited the TGF-ß/Smad2 pathway. In contrast, KIN17 overexpression stimulated TGF-ß/Smad2 pathway in MHCC-97L and HepG2 cells, along with the genes involved in the epithelial-mesenchymal transition. These findings suggest that KIN17 promotes migration and invasion in HCC cells by stimulating the TGF-ß/Smad2 pathway. KIN17 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC.

Polybrominated diphenyl ethers (PBDEs) in household dust: A systematic review on spatio-temporal distribution, sources, and health risk assessment.

Much attention has been paid on polybrominated diphenyl ethers (PBDEs) in household dust due to their ubiquitous occurrences in the environment. Based on the data from 59 articles sampled from 2005 to 2020, we investigated the spatio-temporal distribution, sources, and health risk of 8 PBDE homologues in household dusts worldwide. BDE-209 is the predominant PBDE in household dusts, followed by BDE-99 and BDE-47. The total concentrations of PBDEs (∑8PBDEs) are found to be high in household dusts sampled from 2005 to 2008 and show a significant decline trend from 2009 to 2016 (p < 0.05) and a little upward tendency from 2017 to 2020. The concentrations of PBDEs in household dusts vary greatly in different countries of the world. The use of penta-BDE is the main source of three to five bromo-biphenyl ether monomers contributing 17.4% of ∑8PBDEs, while BDE-209 and BDE-183 are derived from the use of household appliances contributing 82.6% of ∑8PBDEs. Ingestion is the main exposure route for adults and toddlers, followed by dermal contact. The values of hazard index (HI) exposed to PBDEs in household dusts are all less than 1 for both adults and toddlers, indicating a low non-cancer risk. The incremental lifetime cancer risks (ILCRs) of BDE-209 are less than 10-6 for both adults and toddlers, suggesting a negligible risk. However, the total carcinogenic risk of toddlers is higher than that of adults, indicating that much attention should be paid to toddlers exposed to BDE-209 in household dust.

Effect of comorbidity assessed by the Charlson Comorbidity Index on the length of stay, costs, and mortality among colorectal cancer patients undergoing colorectal surgery.

OBJECTIVE: Charlson Comorbidity Index (CCI) is a good predictor for hospitalization cost and mortality among patients with chronic disease. However, the impact of CCI on patients after colorectal cancer surgery is unclear. This study aims to investigate the influence of comorbidity assessed by CCI on length of stay, hospitalization costs, and in-hospital mortality in patients with colorectal cancer (CRC) who underwent surgical resection. METHODS: This historical cohort study collected 10,271 adult inpatients for CRC undergoing resection surgery in 33 tertiary hospitals between January 2018 and December 2019. All patients were categorized by the CCI score into four classes: 0, 1,2, and ≥3. Linear regression was used for outcome indicators as continuous variables and logical regression for categorical variables. EmpowerStats software and R were used for data analysis. RESULTS: Of all 10,271 CRC patients, 51.72% had at least one comorbidity. Prevalence of metastatic solid tumor (19.68%, except colorectal cancer) and diabetes without complication (15.01%) were the major comorbidities. The highest average cost of hospitalization (86,761.88 CNY), length of stay (18.13 days), and in-hospital mortality (0.89%) were observed in patients with CCI score ≥3 compared to lower CCI scores (p < .001). Multivariate regression analysis showed that the CCI score was associated with hospitalization costs (ß, 7340.46 [95% confidence interval (CI) (5710.06-8970.86)], p < .001), length of stay (ß, 1.91[95%CI (1.52-2.30)], p < .001), and in-hospital mortality(odds ratio (OR),16.83[95%CI (2.23-126.88)], p = .0062) after adjusted basic clinical characteristics, especially when CCI score ≥3. Notably, the most specific complication associated with hospitalization costs and length of stay was metastatic solid tumor, while the most notable mortality-specific comorbidity was moderate or severe renal disease. CONCLUSION: The research work has discovered a strong link between CCI and clinical plus economic outcomes in patients with CRC who underwent surgical resection.

Hypertensive vascular and cardiac remodeling protection by allicin in spontaneous hypertension rats via CaMK â ¡/NF-κB pathway.

Allicin is the main active component of Traditional Chinese medicine, garlic. It is widely used to treat cardiovascular diseases. Our previous studies have confirmed that allicin significantly reduces blood pressure in Spontaneous Hypertension Rats (SHRs). However, the reports studying the effect of allicin on vascular and cardiac remodeling caused by hypertension are few, with their underlying mechanism not being studied in detail or fully elucidated. In this study, we treated 12-week-old SHRs with allicin for 4 weeks. After 4 weeks, allicin was shown to improve vascular and cardiac remodeling in SHRs, as evidenced by reduced cardiac left ventricular wall thickness, aortic vessel thickness, and reduced proliferating cell nuclear antigen (PCNA) and smooth muscle actin (α-SMA), and increased expression of and smooth muscle 22α (SM 22α). Additionally, allicin reduced serum IL-1ß, IL-6, and TNF-α levels, improved calcium homeostasis in cardiomyocytes, downregulated calcium transportation-related CaMK II and inflammation-related NF-κB and NLRP3, which were observed in smooth muscle cells and cardiomyocytes. Thus, we inferred that allicin protected hypertensive vascular and cardiac remodeling in Spontaneous Hypertensive Rats by inhibiting the activation of the CaMK II/ NF-κB pathway. This study also provided new mechanistic insights into the anti-hypertensive vascular and cardiac remodeling effects of allicin, highlighting its therapeutic potential.

Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE. Objective: To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE. Methods: We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results: A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21-1.66). No significant publication bias was found in our meta-analysis. Conclusions: In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

Modified Laparoscopic Nephron-Sparing Surgery for Large Renal Hilar Angiomyolipoma: Dual-Center Experience.

Objective: The aim of this study is to evaluate a potential successful strategy for treating large renal hilar angiomyolipoma (RHAML) during the procedure of laparoscopic nephron-sparing surgery (NSS). Methods: The total study population includes 12 patients with large RHAMLs who underwent laparoscopic NSS in the Department of Urology of Fujian Provincial hospital and People's Hospital of Zhejiang, ranging from January 2016 to March 2020. The perioperative variables, intraoperative procedures, and postprocedure complications were all recorded. Three months later, all patients returned to the hospital to check their postoperative recovery by reviewing the computed tomography urography (CTU) image. In the follow-up, patients were asked to have their review by CT or color doppler ultrasound every year. Results: Laparoscopic NSS was successfully performed in all patients. The average operation time was 113.33 ± 33.39 min; the intraoperative blood loss was about 137.50 ± 91.17 ml; the warm ischemia time was 25.25 ± 4.88 min; the drainage tube extubation time was 4.58 ± 2.07 days; and the hospital stay time was 6.42 ± 1.78 days. The average follow-up time was 14.58 ± 9.18 months. After 3 months, all CTU images showed an unobstructed urinary tract in the patient, and no tumor recurrence was found. In addition, no patients had renal atrophy and urine extravasation during follow-up. Conclusions: Laparoscopic NSS for RHAML is complex and technically demanding, but good surgical design and operation can achieve satisfactory surgical results. Modified laparoscopic NSS was a beneficial technique and may provide a reference for treating patients with RHAML.

Ultrasound-guided percutaneous microwave ablation for uterine fibroids: mid-term local treatment efficiency and associated influencing factors.

OBJECTIVE: To investigate the mid-term local treatment efficiency of ultrasound-guided percutaneous microwave ablation (MWA) for uterine fibroids (UFs) and the associated influencing factors. METHODS: From July 2020 to October 2021, a total of 28 patients with 52 UFs who had undergone ultrasound-guided MWA were retrospectively included in this study. Pre-treatment clinical characteristics, conventional ultrasound and contrast-enhanced ultrasound (CEUS) features were analyzed to explore their correlation with volume reduction ratios (VRRs) of sufficient ablation (i.e. a VRR of at least 50% at the 3 month follow-up). The patients were assessed at 1-, 3-, 6 month follow-up after MWA treatment and the assessment included VRR, adverse events, uterine fibroid symptom (UFS) and quality of life (QoL) scores, and clinical symptoms. RESULTS: The procedures of percutaneous MWA for UFs were tolerated well and no major complications occurred in all patients. At the 1-, 3-, 6 month follow-up, the median VRRs of UFs were 30.1%, 46.9%, and 65.8%, respectively. At the 3 month follow-up, 44.4% of fibroids obtained sufficient ablation while the remaining 55.6% obtained partial ablation (i.e. a VRR of <50%). Non-enhancing area during the early phase (i.e. within 30 s after injecting contrast agent) on pre-treatment CEUS was present in 22.2% UFs, which was associated with sufficient ablation at the 3 month follow-up (p < 0.05). In addition, the relevant clinical symptoms of all patients were alleviated or removed. The UFS and QoL score after MWA decreased significantly in comparison with those after MWA (p = 0.04 and p = 0.057, respectively), indicating a remarkable improvement of clinical symptom and QoL. CONCLUSION: Ultrasound-guided MWA is an effective and safe method to treat patients with UFs. Non-enhancing area during the early phase on pretreatment CEUS is associated with mid-term local treatment efficiency, which might be used to predict treatment outcome. ADVANCES IN KNOWLEDGE: Non-enhancing area during the early phase on pretreatment CEUS is an important factor associated with mid-term local treatment efficiency. This is the first study finding that CEUS feature can be used as a marker for the prediction of mid-term local treatment response.

Applicability of 14 Formulas for Estimating Glomerular Filtration Rate in the Evaluation of Renal Function before and after Nephron-Sparing Surgery in Patients with Renal Tumors.

To compare the applicability of 14 equations of estimating glomerular filtration rate (eGFR) before and after nephron-sparing surgery (NSS) for renal function assessment of patients with renal tumors. Preoperative and postoperative GFR is measured by emission computed tomography (ECT) with 99mTc-DTPA as an imaging agent as reference GFR (rGFR) to compare with all formulas. Spearman correlation analysis and Bland-Altman agreement analysis were used to evaluate the correlation between rGFR and eGFR1 to 14 before and after surgery. A total of 50 cases including 22 males and 28 females were included. The results of preoperative eGFR1-14 correlated with rGFR (P < 0.05). The calculation results of all estimation formulas have a significant correlation with preoperative GFR. Preoperative MDRD-I, CKD-EPI SCysC, and FAS Scr-SCysC have good consistency. The CG formula has the highest precision and FAS Scr-SCysC has the highest accuracy. A total of 30 patients followed up after surgery, and postoperative rGFR correlated with CG, CKD-EPI, FAS, and BIS formulas (P < 0.05). But postoperative rGFR has no significant correlation with MDRD and Schwartz (P > 0.05). Postoperative CKD-EPI Scr-SCysC has best consistency, and FAS Scr-SCysC has the highest accuracy and precision. Our data suggest that eGFR equations evaluated by both serum creatinine (Scr) and cystatin C (SCysC) is not necessarily better than those evaluated by one of them alone. Among all enrolled equations, FAS Scr-SCysC is the best one to evaluate postoperative GFR in patients with renal tumors.

Correlation between human papillomavirus infection and reproduction.

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious viruses among men and women of reproductive age throughout the world. Pregnant women are susceptible during pregnancy and most infections of them are self-limiting infections, which can be removed by their autoimmunity, while the persistent infections are associated with precancerous lesions and cancer of the anogenital mucosa in women and men. In addition, HPV infection may also affect reproductive health and fertility. The effect of HPV on female fertility requires further study, but HPV influences sperm parameters. Furthermore, whether HPV infection alters the effect of assisted reproductive technology and whether there is an association between it and assisted reproductive technology (ART) outcomes is unknown. It is considered that the relationship between HPV infection and spontaneous abortion (SA), assisted reproductive technology (ART) outcomes and spontaneous preterm birth (sPTB) has profound implications for the medical care of pregnant and infertile women. This paper reviews the relationship between human papillomavirus infection during pregnancy and SA, sPTB and ART in reproduction, and reviews the relationship between human papillomavirus and human fertility by summarizing the recent domestic and foreign literature.

The effect of preoperative urine culture and bacterial species on infection after percutaneous nephrolithotomy for patients with upper urinary tract stones.

To study the relationship between preoperative urine culture, bacterial species and infection after percutaneous nephrolithotomy in patients with upper urinary tract stones, and summarize the clinical characteristics of different bacterial infections. From January 2014 and January 2020, 963 patients with upper urinary tract stones who underwent PCNL in the department of urology of Fujian provincial hospital were included in the study. Information included the patient's age, gender, weight, diabetes, chronic disease history, urine routine, preoperative urine culture results, stone size, number of stones, hydronephrosis level, operation time, body temperature, heart rate, blood pressure, breathing rate, hemoglobin, serum creatinine, bilirubin, platelets and whether there was preoperative infection were recorded. 141 patients (14.6%) had a positive urine culture before surgery, and 7 of them had multiple bacterial infections. The most common pathogenic bacteria was Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. A total of 74 cases (7.7%) of 963 patients with infection after PCNL occurred, 24 cases (32.4%) of infected patients progressed to urinary septic shock. Univariate analysis shown that the probability of infection in patients with long operation time and positive urine culture was significantly higher, and the difference was statistically significant. Further multivariate logistic regression analysis shown that positive urine culture before operation and long operation time were independent risk factors for infection after PCNL. Among the 29 patients with septic shock, 18 cases (62.1%) had a positive urine culture before surgery. The incidence (43.9%) of postoperative infection in Escherichia coli positive patients was significantly higher than that in the negative group, and the difference was statistically significant. The rate of patients with Escherichia coli infection progressing to septic shock was 9 cases (60%). 2 patients with Enterococcus faecium infection and 2 patients with Klebsiella pneumoniae infection all progressed to septic shock. The age of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 58.53 ± 11.73 years, 76.5 years and 74 years.The body temperature of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 39.10 ± 0.25 °C, 39.45 °C and 38.65 °C. The highest pct value of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 80.62 ± 31.45 ng/mL, 24.32 ng/mL and 8.45 ng/mL. The nitrite positive rate of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 64.51%, 16.6% and 0. Postoperative infection of PCNL is significantly correlated with positive preoperative urine culture, and positive preoperative urine culture is an independent risk factor for postoperative infection. The most common pathogen of postoperative infection of PCNL is Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. Patients with Escherichia coli infection are often positive for nitrite before surgery, mainly manifested by high fever, and PCT is significantly increased (often exceeded 100 ng/ml). Enterococcus faecium and Klebsiella pneumoniae infections mostly occur in elderly patients and often progress to septic shock. Patients with Enterococcus faecium infection have a high fever, and the PCT value is significantly higher (often exceeded 20 ng/ml). Patients with Klebsiella pneumoniae infection have a moderate fever, and the PCT value generally does not exceeded 10 ng/ml. Long operation time is another independent risk factor for PCNL infection.

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis.

OBJECTIVE: To explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes. RESULTS: Seventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results. CONCLUSION: The most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.

Japanese Encephalitis Virus NS1' Protein Interacts with Host CDK1 Protein to Regulate Antiviral Response.

Type I interferon (IFN-I) is a key component of the host innate immune system. To establish efficient replication, viruses have developed several strategies to escape from the host IFN response. Japanese encephalitis virus (JEV) NS1', a larger NS1-related protein, is known to inhibit the mitochondrial antiviral signaling (MAVS)-mediated IFN-ß induction by increasing the binding of transcription factors (CREB and c-Rel) to the microRNA 22 (miRNA-22) promoter. However, the mechanism by which NS1' induces the recruitment of CREB and c-Rel onto the miRNA-22 promoter is unknown. Here, we found that JEV NS1' protein interacts with the host cyclin-dependent kinase 1 (CDK1) protein. Mechanistically, NS1' interrupts the CDC25C phosphatase-mediated dephosphorylation of CDK1, which prolongs the phosphorylation status of CDK1 and leads to the inhibition of MAVS-mediated IFN-ß induction. Furthermore, the CREB phosphorylation and c-Rel activation through the IκBα phosphorylation were observed to be enhanced upon the augmentation of CDK1 phosphorylation by NS1'. The abrogation of CDK1 activity by a small-molecule inhibitor significantly suppressed the JEV replication in vitro and in vivo. Moreover, the administration of CDK1 inhibitor protected the wild-type mice from JEV-induced lethality but showed no effect on the MAVS-/- mice challenged with JEV. In conclusion, our study provides new insight into the mechanism of JEV immune evasion, which may lead to the development of novel therapeutic options to treat JEV infection. IMPORTANCE Japanese encephalitis virus (JEV) is the main cause of acute human encephalitis in Asia. The unavailability of specific treatment for Japanese encephalitis demands a better understanding of the basic cellular mechanisms that contribute to the onset of disease. The present study identifies a novel interaction between the JEV NS1' protein and the cellular CDK1 protein, which facilitates the JEV replication by dampening the cellular antiviral response. This study sheds light on a novel mechanism of JEV replication, and thus our findings could be employed for developing new therapies against JEV infection.

Toward the Practical Use of Cobalt-Free Lithium-Ion Batteries by an Advanced Ether-Based Electrolyte.

The criticality of cobalt (Co) has been motivating the quest for Co-free positive electrode materials for building lithium (Li)-ion batteries (LIBs). However, the LIBs based on Co-free positive electrode materials usually suffer from relatively fast capacity decay when coupled with conventional LiPF6-organocarbonate electrolytes. To address this issue, a 1,2-dimethoxyethane-based localized high-concentration electrolyte (LHCE) was developed and evaluated in a Co-free Li-ion cell chemistry (graphite||LiNi0.96Mg0.02Ti0.02O2). Extraordinary capacity retentions were achieved with the LHCE in coin cells (95.3%), single-layer pouch cells (79.4%), and high-capacity loading double-layer pouch cells (70.9%) after being operated within the voltage range of 2.5-4.4 V for 500 charge/discharge cycles. The capacity retentions of counterpart cells using the LiPF6-based conventional electrolyte only reached 61.1, 57.2, and 59.8%, respectively. Mechanistic studies reveal that the superior electrode/electrolyte interphases formed by the LHCE and the intrinsic chemical stability of the LHCE account for the excellent electrochemical performance in the Co-free Li-ion cells.