The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

【Objective】 To investigate the mechanism of atorvastatin improving ventricular remodeling in rats with myocardial infarction. 【Methods】 Ligation of left anterior descending coronary artery was performed to establish rat model of myocardial infarction. Thirty rats were divided into sham group(n=10), myocardial infarction group(n=10) and atorvastatin group(n=10). Echocardiography was used to examine cardiac function and left ventricular mass index(LVMI) was calculated. The content of arginine vasopressin(AVP) in left ventricular non-infarct area and serum was measured by ELISA. Masson staining was used to observed interstitial fibrosis of myocardium. Immunohistochemistry was used to measure the expression of type Ⅰ collagen. The protein expression of transforming growth factor-β1(TGF-β1) was detected by western blot. 【Results】 After 5 weeks, the number of rats in sham group, myocardial infarction group and atorvastatin group was 10, 9 and 10, respectively. Compared with sham group, LVEF was significantly decreased and, LVMI, interstitial fibrosis, the content of AVP, the expression of type Ⅰ collagen and TGF-β1 in the left ventricular non-infarct area were significantly increased in myocardial infarction group and atorvastatin group(P<0.05). Atorvastatin significantly increased LVEF and decreased interstitial fibrosis, the content of AVP, the expression of type Ⅰ collagen and TGF-β1 in the left ventricular non-infarct area(P<0.05) . 【Conclusion】 Atorvastatin could ameliorate ventricular remodeling in rats with myocardial infarction, which might be associated with inhibiting the expression of AVP and TGF-β1.

Novel antineoplastic drugs have significantly prolonged the survival time of cancer patients. Meanwhile, nephrotoxicity of antineoplastic drugs and its adverse effects on the prognosis of cancer patients have received increasing attention. Conventional chemotherapy causes kidney injury mainly through direct renal toxicity, while new anti-tumor drugs can induce a number of kidney damage, including acute renal tubular injury, thrombotic microangiopathy, interstitial nephritis, and glomerular diseases through multiple mechanisms. Clinicians must be knowledgeable in the renal toxicity of antineoplastic drugs to minimize the nephrotoxicity of the drugs and diagnose early, especially in patients with underlying kidney disease. This article focuses on the risk factors, clinical and histological patterns, pathogenesis, prevention and treatment of renal injury associated with the antineoplastic drugs, especially novel targeted antineoplastic drugs.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)

Objective To analyze the status of quality indicators(QI) on specimen acceptability and establish preliminary qual ity specification.Methods Web based External Quality Assessment system was used to collect data of laboratories partici pated in "Medical quality control indicators in clinical laboratory" from 2015 to 2017,including once in 2015 and 2017 and twice in 2016.Rate and sigma scales were used to evaluate incorrect sample type,incorrect sample container,incorrect fill level and anticoagulant sample clotted.The 25th percentile (P25) and 75th percentile (P75) of the distribution of each QI were employed to establish the high,medium and low specification.Results 5 346,7 593,5 950 and 6 874 laboratories sub mitted the survey results respectively.The P50 of biochemistry (except incorrect fill level),immunology and microbiology reach to 6σ.The P50 of clinical laboratory is 4 to 6σ except for incorrect sample container.There is no significant change of the continuous survey results.Based on results in 2017 to establish the quality specification,the P25 and P75 of the four QIs is 0 and 0.084 4 ％,0 and 0.047 6 ％,0 and 0.114 2 ％,0 and 0.078 4 ％,respectively.Conclusion According to the results of the survey,most laboratories had a faire performance in biochemistry,immunology and microbiology,and clinical laboratory needs to be strengthened.Laboratories should strengthen the laboratory information system construction to ensure the actual and reliable data collection,and make a long time monitoring to achieve a better quality.

Objective To explore the strategy and countermeasures of Oncomelania hupensis snail control and evaluate the effect in inside-embankment areas of lake-type schistosomiasis endemic area,for providing the effective method for controlling and interrupting the schistosomiasis transmission. Methods The data of schistosomiasis epidemic and its control and preven-tion were collected in Junshan District,Hunan Province,and the effect of snail control countermeasures were evaluated and the trend of indexes of snails was drafted in the inside-embankment areas of Junshan District,Hunan Province from 1998 to 2007. Results The area with snails in the inside embankment areas of Junshan District decreased by 98.43%,from 1496.66 hm2 in 1998 to 23.48 hm2 in 2017. The occurrence rate and average density of of living snails decreased from 20.61%and 0.45 snail/0.1 m2 in 2003 to 2.06%and 0.03 snail/0.1 m2 in 2017. The highest area with schistosome infected snails was found in 2001 and the total area was 79.36 hm2,however,no infected snails were found since 2007. The total fiscal investment for schistosomiasis pre-vention and control was 398.857 million RMB in Junshan District,including molluscicide(81.7709 million RMB)and environ-ment reform(213.5 million RMB)respectively. Conclusion The comprehensive measures,mainly including the combination of molluscicide and environment reform have gotten a significant effect in snail control and elimination in the inside-embankment areas,but the snail surveillance still need to be strengthened in the historic areas with snails.

Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course,and available treatments for delaying the progression to end-stage renal disease are limited.This study aimed to assess the efficacy and safety of the traditional Chinese medicine,Niaoduqing particles,for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective,randomized,double-blind,placebo-controlled,multicenter clinical trial.From May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml,min-1· 1.73 m-2,aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces.Patients were randomized in a 1∶1 ratio to either a test group,which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks,or a control group,which was administered a placebo using the same methods.The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment.The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test.The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis.At 24 weeks,the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups,respectively (Z =2.642,P =0.008),and the median change in eGFR was-0.2 (-4.3-2.7) and-2.2 (-5.7-0.8) ml·min-1.1.73 m-2,respectively (Z =-2.408,P =0.016).There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD.This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

OBJECTIVETo investigate clinical outcomes of tendon allograft reconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury.

METHODSForty-eight patients with knee dislocation were reconstructed anterior and posterior ligament under arthroscopy at stage I from January 2008 to January 2012, and repaired ligaments injury of knee joint by minimally invasive technique. There were 38 males and 10 females aged from 20 to 59 years old with an average of 35.6 years old; 22 cases on the left side and 26 cases on the right side; the time from injury to operation ranged from 2 d to 2 weeks. Two cases combined with anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL) and posterolateral complex injuries, 36 cases combined with ACL, PCL, and MCL injuries, 10 cases combined with ACL, PCL and PLC injuries; 4 cases combined with peroneal nerve injury. Lysholm scoring were used to compared the cases before operation and final following-up to evaluate knee function.

RESULTSAll patients were followed up from 12 to 30 months with an average of (18.2 ± 6.3) months. Activity and stability of joint were obviously improved. Lysholm score were improved from 40.3 ± 4.1 before operation to 87.0 ± 6.4 at final following-up.

CONCLUSIONReconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury could recover stability of joint better,reserve joint function. Preoperative training and postoperative individualized rehabilitation treatment is the key point of recover knee joint function.

Adult ; Anterior Cruciate Ligament Injuries ; Arthroscopy ; Female ; Humans ; Knee Dislocation ; rehabilitation ; surgery ; Male ; Middle Aged ; Multiple Trauma ; surgery ; Posterior Cruciate Ligament ; injuries ; Reconstructive Surgical Procedures ; methods

OBJECTIVETo investigate the effectiveness of surgical strategies for Shang Ring circumcision in the treatment of short frenulum praeputii in patients with redundant prepuce or phimosis.

METHODSTotally, 130 cases of short frenulum praeputii with redundant prepuce or phimosis were randomly assigned to an experimental group and a control group of equal number to receive Shang Ring circumcision, the former by transverse incision in the distal penis foreskin and pull-up of the interior board, and the latter by conventional transverse incision and longitudinal suture of the frenulum praeputii. Comparisons were made between the two groups in the surgical duration, intraoperative blood loss, 24 h postoperative pain visual analog score (VAS), postoperative complications, satisfaction with the penile appearance, and the quality of sexual life.

RESULTSThe surgical duration, intraoperative blood loss, 24 h postoperative VAS, postoperative sexual satisfaction, and satisfaction with penile appearance were (4.60 +/- 1.20) min, (2.61 +/- 1.81) ml, 1.73 +/- 0.76, 98.5%, and 98.5%, respectively, in the experimental group, as compared with (21.60 +/- 6.30) min, (11.10 +/- 3.40) ml, 5.37 +/- 1.84, 70.3% and 69.8% in the control, with statistically significant differences between the two groups (P < 0.05). The incidence rates of such major complications as wound dehiscence, infection, and moderate to severe edema were 1.5% (1/65), 3.1% (2/65), and 4.6% (3/65), respectively, in the experimental group in comparison with 12.3% (8/65), 15.3% (10/65), and 30.7% (20/65) in the control, with statistically significant differences between the two groups (P < 0.05). None of patients had any serious complications.

CONCLUSIONShang Ring circumcision by transverse incision in the distal penis foreskin and pull-up of the interior board, with its advantages of shorter operation time, less blood loss, mild pain, fewer complications, and higher satisfaction and acceptance of the patients, can be used as an safe and effective approach to the treatment of short frenulum praeputii.

Aged ; Blood Loss, Surgical ; statistics & numerical data ; Circumcision, Male ; adverse effects ; instrumentation ; methods ; Edema ; epidemiology ; Foreskin ; abnormalities ; surgery ; Humans ; Incidence ; Male ; Operative Time ; Pain Measurement ; Pain, Postoperative ; diagnosis ; Patient Satisfaction ; Phimosis ; surgery ; Postoperative Period ; Prostheses and Implants ; Surgical Wound Dehiscence ; epidemiology ; Surgical Wound Infection ; epidemiology