Efficacy and Safety of Acupuncture for Restless Legs Syndrome in Patients with End-Stage Renal Disease: A Randomized-Controlled Trial at Hospital-Based Hemodialysis Center.

Background: Restless legs syndrome (RLS) is frequent in patients with hemodialysis (HD) and occurs predominantly in its most severe forms. The study was conducted to evaluate the efficacy and safety of acupuncture for RLS in patients with end-stage renal disease (ESRD) at hospital-based HD center. Methods: This single-blind, randomized controlled trial was performed on patients with HD and RLS who were randomly assigned to the experimental group and control group. Data were collected using the International Restless Legs Syndrome Rating Scale (IRLSRS), Insomnia Severity Index (ISI), and heart rate variability (HRV) records at baseline, after the therapeutic course (12 times/4 weeks), and 1-week follow-up. Result: A total of 47 patients were evaluated with IRLSRS score from 11 to 30 in this study. There were 41 patients enrolled in the study based on inclusion/exclusion criteria and allocated randomly into two groups. A total of 35 participants completed the trial, including 18 subjects in the experimental group and 17 subjects in the control group. The comparison of IRLSRS and ISI showed a significant reduction between two groups after acupuncture treatment (p = 0.002, p = 0.003). The ISI after 1-week follow-up also revealed significant decrease (p = 0.003). This HRV results showed that high frequency (HF%) increased significantly (p = 0.021) and low frequency (LF%) decreased significantly in the acupuncture group (p = 0.021). The generalized estimating equation showed that the IRLSRS improved by 2.902 points (p < 0.001) in the acupuncture group compared with the control group and by 1.340 points (p = 0.003) after 1-week follow-up. There were no adverse effects observed during HD in this study. Discussion: The authors conclude that acupuncture could effectively improve the symptoms of RLS significantly. The results from this study provide clinical evidence on the efficacy and safety of acupuncture to treat the patients with RLS at the HD center.

Alkaloids from Zanthoxylum nitidum and their anti-proliferative activity against A549 cells by regulating the EGFR/AKT/mTOR pathway.

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum, we isolated ten alkaloids (1-10), including one new natural compound (1), and nine known alkaloids (2-10), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases.

Chitinase-3-like protein-1 (CHI3L1), also known as YKL40, is a glycoprotein that belongs to the chitinase protein family. It is involved in various biological functions, including cell proliferation and tissue remodeling, with inflammatory and immunomodulatory capabilities. Several studies have shown that CHI3L1(YKL40) is upregulated in various diseases, such as cancer, asthma, and inflammatory bowel disease, among others. Although the expression level of CHI3L1(YKL40) is associated with disease activity, severity, and prognosis, its potential as a therapeutic target is still under investigation. In this review, we summarize the biological functions, pathological roles, and potential clinical applications of specific inhibitors and targeted therapies related to CHI3L1(YKL40).

Novel method for laparoscopic rectus sheath tunneling with Lin's tube in peritoneal dialysis catheter implantation.

Laparoscopic implantation of a catheter through rectus sheath tunnel minimizes the risks of catheter failure and reduces some complications like catheter migration, hernias, and leaks. We described a novel method for laparoscopic catheter rectus sheath tunneling using an aspiration tube and a silk tie (Lin's tube). This material is easily available and yields a small fascial defect with an equivalent cannula size to minimize tissue disruption. The technique is feasible, reproducible and it may reduce the risks of postoperative leakage and hemorrhage.

Predicting hyperkalemia in patients with advanced chronic kidney disease using the XGBoost model.

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). Hyperkalemia is associated with mortality, CKD progression, hospitalization, and high healthcare costs in patients with CKD. We developed a machine learning model to predict hyperkalemia in patients with advanced CKD at an outpatient clinic. METHODS: This retrospective study included 1,965 advanced CKD patients between January 1, 2010, and December 31, 2020 in Taiwan. We randomly divided all patients into the training (75%) and testing (25%) datasets. The primary outcome was to predict hyperkalemia (K+ > 5.5 mEq/L) in the next clinic vist. Two nephrologists were enrolled in a human-machine competition. The area under the receiver operating characteristic curves (AUCs), sensitivity, specificity, and accuracy were used to evaluate the performance of XGBoost and conventional logistic regression models with that of these physicians. RESULTS: In a human-machine competition of hyperkalemia prediction, the AUC, PPV, and accuracy of the XGBoost model were 0.867 (95% confidence interval: 0.840-0.894), 0.700, and 0.933, which was significantly better than that of our clinicians. There were four variables that were chosen as high-ranking variables in XGBoost and logistic regression models, including hemoglobin, the serum potassium level in the previous visit, angiotensin receptor blocker use, and calcium polystyrene sulfonate use. CONCLUSIONS: The XGBoost model provided better predictive performance for hyperkalemia than physicians at the outpatient clinic.

Can chronic kidney disease staging early predict outcome of large-artery ischemic stroke with impaired renal function?

Background: Ischemic stroke poses a major threat to human beings, and a prompt intravenous thrombolytic management remains the gold standard protocol for stroke sufferers. Although the role of thrombolytic therapy (r-tPA) for ischemic stroke patients and those with underlying impaired renal function has been advocated as effective treating strategy, there is still a lack of investigation as to finding out baseline important variables that are capable of early outcome prediction. Objectives: In this project, we hypothesize that the change of clinical chronic kidney disease (CKD) staging (delta stage = CKD stage after 3-month follow-up - CKD stage at admission) could serve as a crucial predictor of the prognosis of patients. Design: This is a cohort longitudinal retrospective study. Sources and Methods: A total of 765 cerebral artery ischemic stroke patients with impaired renal function were recruited and followed up for 1 year. Among them, 116 had received the thrombolytic treatment (r-tPA) after being evaluated at the triage in the emergency department and the rest had not (non-r-tPA). Propensity-matching was applied to compare the mortality between the r-tPA and non-r-tPA groups. Multiple logistic regression (LR) and decision tree (DT) algorithm were used to identify important prediction factors for mortality as well as the improvement in neurological function. Results: The 1-year mortality rates for r-tPA and non-r-tPA groups were 32.8% and 44.4%, respectively. The propensity-matched odds ratio of mortality for the r-tPA group compared with the non-r-tPA group is 0.469, with p = 0.003. Logistic regressions suggest that age, Hct, diabetes mellitus type 2, coronary artery disease, and delta stage are important factors for mortality for the non-r-tPA group, whereas age, diabetes mellitus type 2, chronic heart failure, hospital day, and delta stage are important factors for the r-tPA group. On the usage of antihypertensive drugs, ACEI/ARB was not associated with mortality (p = 0.198), whereas the diuretic was, with odds ratio at 1.619 (p = 0.025), indicating higher mortality after administration. Both LR and DT analyses indicate that delta stage is the most important predictor. For the r-tPA group, patients with delta stage ⩽0 had a 24% mortality, while that for delta stage >0 the mortality is 75%. For non-r-tPA patients, the corresponding mortalities were 30.9 and 66.3, respectively. Delta stage is also useful for predicting patients' improvement of neurological function, assessed by NIHSS, mRS, and Barthel Index. The areas under the curve for the three assessments are 0.83, 0.835, and 0.663, respectively. Conclusion: Large-artery ischemic stroke patients who received thrombolytic treatment had significantly lower mortality, even when presenting underlying impaired renal function. The change of CKD staging (delta stage) is capable of acting as a powerful clinical baseline surrogate for both r-tPA and non-r-tPA patients in terms of early outcome prediction. Long-term use of diuretics could be potentially harmful to this group of patients. Moreover, delta stage correlates well with clinical long-term neurological functionality assessment (NIHSS, mRS, and Barthel index), which is helpful in aiding urgent clinical decision-making.

Serum globulin is a novel predictor of mortality in patients undergoing peritoneal dialysis.

Serum globulin, which is composed mainly of immunoglobulins and acute phase proteins, can be considered as reflecting the inflammatory state. We conducted the present study to investigate the role of globulin in mortality risk in patients undergoing peritoneal dialysis (PD). The study participants were categorized by the median globulin value (2.8 g/dL) as the high globulin group (≥ 2.8 g/dL), and low globulin group (< 2.8 g/dL). Serum globulin is calculated by the equation: (serum total protein-serum albumin). The area under the curve (AUC) by the receiver operating characteristics curve analysis was calculated to compare the mortality prediction capacity of globulin with that of ferritin, and WBC counts. Among the 554 patients, 265 (47.83%) were men, the mean age was 52.91 ± 15.54 years and the body mass index was 23.44 ± 3.88 kg/m2. Multivariate Cox models showed the high globulin group had higher mortality risks of all-cause and cardiovascular disease (CVD), compared with the low globulin group with adjusted HRs of 2.06 (95% CI 1.39-3.05) and 1.94 (95% CI 1.18-3.16), respectively. The AUC of univariate and multivariate models for all-cause mortality resulted in higher AUC values for globulin than for ferritin and white blood cell (WBC) counts. In patients undergoing PD, the serum globulin can serve as a novel and independent determinant of predicting overall and CVD- associated mortality.

The impact of acute kidney injury with or without recovery on long-term kidney outcome in patients undergoing living liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not. METHODS: Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) was investigated. RESULTS: A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12-2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95-4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD. CONCLUSIONS: Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up.

Flanged Bentall Plus Cabrol Procedure for Interventricular Septal Dissection in Behçet's Disease.

Behçet's disease with interventricular septal dissection is extremely rare, and its surgical treatment is even more challenging. One such treatment with interventricular septal dissection repair was followed by the flanged Bentall and Cabrol techniques. The flange of the flanged composite graft was attached to the left ventricular outflow tract instead of the fragile annulus. The Cabrol procedure was performed to reduce anastomotic tension at the coronary button sites. Good short-term results were achieved.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle.@*METHODS@#A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence.@*RESULTS@#After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling.@*CONCLUSION@#Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Association between predialysis creatinine and mortality in acute kidney injury patients requiring dialysis.

BACKGROUND: Creatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed. METHODS: We extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset. RESULTS: In all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29-2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset. CONCLUSIONS: In patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status.

Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is usually diagnosed at an advanced stage and has poor prognosis. Theranostic agents are the current trend in drug development, but are lacking in EOC. YKL40 is predominantly expressed and involved in tumorigenesis in EOC. In this study, we developed a companion theranostic agent targeting YKL40. We measured YKL40 expression levels in ascites using ELISA and correlated them with the clinical outcomes of patients with EOC. We developed radionuclide labeled In-111/Lu-177-DTPA-YKL40 neutralizing antibodies and investigated their radiochemical purity, SPECT/CT imaging, bio-distribution, and therapeutic responses in ovarian cancer xenograft mice. We demonstrated that YKL40 expression levels in ascites were significantly higher in EOC patients with serous histological type, high tumor grade, advanced stage, tumor recurrence, chemoresistance, and tumor-related death. The radiochemical purity of In-111/Lu-177-DTPA-YKL40 neutralizing antibodies reached more than 90% after 24 h of labeling. SPECT/CT imaging showed significant accumulation of In-111-DTPA-YKL40 and Lu-177-DTPA-YKL40 antibodies at the tumor site of ovarian cancer xenograft mice 24 h after administration. Lu-177-DTPA-YKL40 antibodies significantly inhibited tumor growth in ovarian cancer xenograft mice. Our study indicated that In-111/Lu-177-DTPA-YKL40 neutralizing antibodies could be potential companion theranostic agents for patients with EOC.

Infection in Living Donor Liver Transplantation Leads to Increased Risk of Adverse Renal Outcomes.

(1) Background: Little is known about the subsequent renal function change following incident infectious diseases in living-donor liver transplant (LT) recipients. (2) Methods: We studied patients who underwent living-donor LT from January 2003 to January 2019 to evaluate the association of incident hospitalization with major infections or pneumonia with adverse renal outcomes, including a sustained 40% reduction in estimated glomerular filtration rate (eGFR) and renal composite outcome (a 40% decline in eGFR, end-stage renal disease, or death.). Multivariable-adjusted time-dependent Cox models with infection as a time-varying exposure were used to estimate hazard ratio (HR) with 95% confidence interval (CI) for study outcomes. (3) Results: We identified 435 patients (mean age 54.6 ± 8.4 years and 76.3% men), of whom 102 had hospitalization with major infections during follow-up; the most common cause of infection was pneumonia (38.2%). In multiple Cox models, hospitalization with a major infection was associated with an increased risk of eGFR decline > 40% (HR, 3.32; 95% CI 2.13−5.16) and renal composite outcome (HR, 3.41; 95% CI 2.40−5.24). Likewise, pneumonia was also associated with an increased risk of eGFR decline > 40% (HR, 2.47; 95% CI 1.10−5.56) and renal composite outcome (HR, 4.37; 95% CI 2.39−8.02). (4) Conclusions: Our results illustrated the impact of a single infection episode on the future risk of adverse renal events in LT recipients. Whether preventive and prophylactic care bundles against infection and judicious modification of the immunosuppressive regimen benefit renal outcomes may deserve further study.

Predicting Mortality Using Machine Learning Algorithms in Patients Who Require Renal Replacement Therapy in the Critical Care Unit.

Background: General severity of illness scores are not well calibrated to predict mortality among patients receiving renal replacement therapy (RRT) for acute kidney injury (AKI). We developed machine learning models to make mortality prediction and compared their performance to that of the Sequential Organ Failure Assessment (SOFA) and HEpatic failure, LactatE, NorepInephrine, medical Condition, and Creatinine (HELENICC) scores. Methods: We extracted routinely collected clinical data for AKI patients requiring RRT in the MIMIC and eICU databases. The development models were trained in 80% of the pooled dataset and tested in the rest of the pooled dataset. We compared the area under the receiver operating characteristic curves (AUCs) of four machine learning models (multilayer perceptron [MLP], logistic regression, XGBoost, and random forest [RF]) to that of the SOFA, nonrenal SOFA, and HELENICC scores and assessed calibration, sensitivity, specificity, positive (PPV) and negative (NPV) predicted values, and accuracy. Results: The mortality AUC of machine learning models was highest for XGBoost (0.823; 95% confidence interval [CI], 0.791−0.854) in the testing dataset, and it had the highest accuracy (0.758). The XGBoost model showed no evidence of lack of fit with the Hosmer−Lemeshow test (p > 0.05). Conclusion: XGBoost provided the highest performance of mortality prediction for patients with AKI requiring RRT compared with previous scoring systems.

Association of Albumin and Globulin with Mortality Risk in Incident Peritoneal Dialysis Patients.

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9−3.8) g/dL for albumin and 2.8 (2.5−3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83−8.20, p < 0.001) and 5.65 (95% CI 2.23−14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.

Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer.

The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake in HCT-116 cells. Then, subcutaneous HCT-116 xenograft tumors were used for ex vivo biodistribution, antitumor efficacy, and histochemical analysis studies. Results of cellular uptake and ex vivo biodistribution of SN-38/Sunitinib micelles showed the highest accumulation in tumors compared with other normal organs. In the antitumor effect studies, mice bearing HCT-116 tumors were smallest at day 28 after injection of SN-38/Sunitinib micelles, compared with other experiment groups (p < 0.01). As demonstrated by the results of inhibition on multi-receptors by Sunitinib, we confirmed that SN-38/Sunitinib co-loaded micelles to be a treatment modality that could inhibit VEGF and PDGF receptors and enhance the antitumor effect of SN-38 (p < 0.05). In summary, we consider that this micelle is a potential formulation for the combination of SN-38 and Sunitinib in the treatment of colorectal cancer.

Micro-Elimination of Hepatitis C among Patients with Kidney Disease by Using Electronic Reminder System-A Hospital-Based Experience.

BACKGROUND: Little is known about the use of an electronic reminder system for HCV screening among patients with kidney disease. In this study, we tried to determine whether reminder systems could improve the HCV screening rate in patients with kidney disease. METHODS: Patients with kidney disease were enrolled from August 2019 to December 2020 to automatically screen and order HCV antibody and RNA testing in outpatient departments. RESULTS: A total of 19,316 outpatients with kidney disease were included, and the mean age was 66.5 years. The assessment rate of HCV antibody increased from 53.1% prior to the reminder system to 79.8% after the reminder system (p < 0.001), and the assessment rate of HCV RNA increased from 71% to 82.9%. The anti-HCV seropositivity rate decreased from 7.3% at baseline to 2.5% after the implementation of the reminder system (p < 0.001), and the percentage of patients with detectable HCV RNA among those with anti-HCV seropositivity decreased from 69.1% at baseline to 46.8% (p < 0.001). CONCLUSIONS: The feasibility of an electronic reminder system for HCV screening among patients with kidney disease in a hospital-based setting was demonstrated.

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

Lupus nephritis with corticosteroid responsiveness: molecular changes of CD46-mediated type 1 regulatory T cells.

BACKGROUND: The engagement of the complement regulatory proteins CD46 and CD3 in human CD4+ T cells induces the type 1 regulatory T cells (Tr1) and interleukin-10 (IL-10) secretion. This study aimed to elucidate the molecular changes of Tr1 cells through CD46 cytoplasmic Cyt1 tail in lupus nephritis (LN) respond to intravenous methylprednisolone (ivMP) therapy. METHODS: We enrolled 40 pediatric patients with LN and 30 healthy controls. Clinical characteristics and peripheral blood mononuclear cells were collected before and 3 days after the administration of ivMP. Kidney specimens were taken from five LN and five minimal-change nephrotic syndrome patients. RESULTS: We found that defective CD46-mediated T-helper type 1 contraction (IL-10 switching) is present in active LN patients. The ivMP therapy enhanced LN remission, restored the production of IL-10, increased the CD46-Cyt1/Cyt2 ratio, AKT, and cAMP-responsive element-binding protein phosphorylation, and induced migration with the expression of chemokine receptor molecules CCR4, CCR6, and CCR7 of CD3/CD46-activated Tr1 cells. CONCLUSIONS: Pharmacologic interventions that alter the patterns of CD46-Cyt1/Cyt2 expression and the secretion of IL-10 by CD3/CD46-activated Tr1 cells can be used in patients with active LN. IMPACT: In patients with LN, ivMP was associated with increased IL-10 production and increased CD46-Cyt1/Cyt2 ratio and AKT phosphorylation by Tr1 cells, with enhanced potential to migration in response to CCL17. These results suggest that expression levels of CD46 isoforms Cyt1 and Cyt2 in CD4 + CD46 + Tr1 cells differ in patients with active LN but can be corrected by corticosteroid treatment. Enhancing the expression of functional CD4 + CD46 + Tr1 cells may be a useful therapeutic approach for LN.