Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Effect of non-pharmacological treatment on the full recovery of social functioning in patients with attention deficit hyperactivity disorder

BACKGROUND Long-term treatment of attention deficit/hyperactivity disorder(ADHD)is associated with adverse events,such as nausea and vomiting,dizziness,and sleep disturbances,and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients’social functioning.AIM To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD.METHODS A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group(methylphenidate hydrochloride and tomoxetine hydrochloride)or the non-pharmacological group(parental training,behavior modification,sensory integration therapy,and sand tray therapy),with 45 cases in each group.Outcome measures included treatment compliance,Swanson,Nolan,and Pelham,Version IV(SNAP-IV)scores,Conners Parent Symptom Questionnaire(PSQ)scores,and Weiss Functional Impairment Rating Scale(WFIRS)scores.RESULTS The non-pharmacological interventions resulted in significantly higher compliance in patients(95.56%)compared with medication(71.11%)(P<0.05).However,no significant differences in SNAP-IV and PSQ scores,in addition to the learning/school,social activities,and adventure activities of the WFIRS scores were observed between the two groups(P>0.05).Patients with non-pharmacological interventions showed higher WFIRS scores for family,daily life skills,and self-concept than those in the pharmacological group(P<0.05).CONCLUSION Non-pharmacological interventions,in contrast to the potential risks of adverse events after longterm medication,improve patient treatment compliance,alleviate patients’behavioral symptoms of attention,impulsivity,and hyperactivity,and improve their cognitive ability,thereby improving family relationships and patient self-evaluation.

Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function

Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.

Dominant-negative inhibition of glucose-dependent insulinotropic polypeptide impairs function of β cells in transgenic pigs

Dear Editor： Glucose-dependent insulinotropic polypeptide （GIP） and proglucagon product glucagon-like peptide-1 （GLP- 1） and their corresponding receptors promote secretion of glucose-dependent insulin and may be responsible for up to 70% of postprandial insulin secretions.

Impairment of the Regulation of Gonadal Function in Channa punctatus by Metacid-50 and Carbaryl under Laboratory and Field Conditions

Regulation of gonadal function by gonadotropic hormone (GtH) and gonadotropin-releasing hormone (GnRH) in Channa punctatus was significantly affected by nonlethal levels of Metacid-50 and Carbaryl. Under laboratory conditions, the time-dependent decrease in serum GtH level was higher in Carbaryl-treated fish than in Metacid-50-treated fish. The situation was reversed in the field, with a higher inhibitory effect of Metacid-50 being recorded. On the other hand, pituitary GtH content and GnRH activity were inhibited to a greater extent by Metacid-50 than by Carbaryl under both field and laboratory conditions. The present findings highlight that even low doses of Metacid-50 and Carbaryl are effective enough to cause reproductive damage, as evidenced by homeostatic unbalance of the reproductive regulatory system. 1990 Academic Press. Inc.

Prevalence of Uropathogenic Escherichia coli among Adult Male Patients 40 Years and above with Haematuria and Impaired Kidney Attending General Hospitals in Benue State

Haematuria is the presence of red blood cells in urine. It is most often caused by urinary tract infections of which Escherichia coli is frequently implicated. Impairment of kidney functions could occur as a result of infection or other complications of the kidney. The aim of the study was to determine the prevalence of uropathogenic Escherichia coli among adult male patients with haematuria and impaired kidneys attending a general hospital in Benue state. Three hundred and sixty-eight (368) samples of urine were collected from 368 male patients (≥ 40 years) attending the 23 general hospitals in Benue state. Each of the urine samples was divided into two parts for haematuria and isolation and identification of Escherichia coli. Blood samples (368) were also collected from the patients and used for quantitative determination of creatinine and estimation of glomerular filtration rate. The presence of haematuria was 45.1% and ranges from 12.5% to 100%. Prevalence of haematuria with respect to age shows that patients within the age group of 90 - 99 years had the highest rate (100%) and the least were those within the ages of 40 - 49 years (20.0%). Isolation rate of uropathogenic Escherichia coli was 16.3% and ranged from 6.3 to 37.5%. Patients within the age group of 90 - 99 years had the highest elevated impaired renal function of 4 (80%), followed by patients within the ages of 80 - 89 years [17 (77.3%)] and the lowest were those within the ages of 40 - 49 [6 (10.0%)]. The overall presence of haematuria in the patients was high (45.1%) with similar high Escherichia coli isolation rate and impaired renal function which could mean that acute or chronic kidney disease may set in.

Protein post-translational modifications after spinal cord injury

Deficits in intrinsic neuronal capacities in the spinal cord,a lack of growth support,and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating consequences.As such,one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal growth.Among these factors,a series of individual protein level disorders have been identified during the generation of axons following spinal cord injury.Moreover,an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal growth.Some researchers have discovered a variety of post-translational modifications after spinal cord injury,such as tyrosination,acetylation,and phosphorylation.In this review,we reviewed the post-translational modifications for axonal growth,functional recovery,and neuropathic pain after spinal cord injury,a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.

Resective surgery for liver tumor: a multivariate analysis of causes and risk factors linked to postoperative complications

BACKGROUND: In spite of accurate selection of patients eligible for resection, and although advances in surgical techniques and perioperative management have greatly contributed to reducing the rate of perioperative deaths, stress must be placed on reducing the postoperative complication rates reported to be still as high as 50%. This study was designed to analyze the causes and foreseeable risk factors linked to postoperative morbidity on the grounds of data derived from a single-center surgical population. METHODS: From September 1989 to March 2005, 287 consecutive patients, affected either with HCC or liver metastasis, had liver resection at our department. Among the HCC series we recorded 98 patients (73.2%) in Child- Pugh class A, 32 (23.8%) in class B and 4 in class C (3%). In 104 colorectal metastases, 71% were due to colon cancer, 25% rectal, 3% sigmoid, and 1% anorectal. In 49 non-colorectal metastases, 22.4% were derived from breast cancer, 63.2% gastrointestinal tumors (excluding colon) and 14.4% other cancers. We performed 80 wedge resections, 77 bisegmentectomies and/or left lobectomies, 74 segmentectomies, 22 major hepatectomies, 20 left hepatectomies, and 14 trisegmentectomies. RESULTS: The in-hospital mortality rate in this series was 4.5%, and the morbidity rate was 47.7%, because of pleural effusion (30%), hepatic abscess (25%), hepatic insufficiency (19%), ascites (10%), hemoperitoneum (10%), or biliary fistula (6%). The variables associated with the technical aspects of the surgical procedure thatwere responsible for the complications were: a Pringle maneuver length more than 20 minutes (P=0.001); the type of liver resection procedure, including major hepatectomy (P=0.02), left hepatectomy (P=0.04), trisegmentectomy (P=0.04), bisegmentectomy and/or left lobectomy (P=0,04); and a blood transfusion of more than 600 ml (P=0.04). CONCLUSION: The evaluation of causes and foreseeable risk factors linked to postoperative morbidity during the planning of surgical treatment should play the same role as other factors weighed in the selection of patients eligible for liver resection.

Changes of auditory evoked magnetic fields in patients after acute cerebral infarction using magnetoencephalography

Auditory evoked magnetic fields were recorded from 15 patients with acute cerebral infarction and 11 healthy volunteers using magnetoencephalography.The auditory stimuli of 2 kHz pure tone were binaurally presented with an interstimulus interval of 1 second.The intensity of stimuli was 90 dB and the stimulus duration was 8 ms.The results showed that the M100 was the prominent response, peaking approximately 100 ms after stimulus onset in all subjects.It originated from the area close to Heschl’s gyrus.In the patient group,the peak latency of M100 responses was significantly prolonged,and the mean strength of equivalent current dipole was significantly smaller in the affected hemisphere.The three-dimensional inter-hemispheric difference of the M100 positions was increased in the patient group.Our experimental findings suggested that impairment of cerebral function in patients with acute ischemic stroke can be detected using magnetoencephalography with the higher spatial resolution and temporal resolution.Magnetoencephalography could provide objective and sensitive indices to estimate auditory cortex function in patients with acute cerebral infarction.

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19

Gastrointestinal(GI)symptoms,such as diarrhea,abdominal pain,vomiting,and anorexia,are frequently observed in patients with coronavirus disease 2019(COVID-19).However,the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections remain elusive.Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2(ACE2)receptors resulting in impaired barrier function.While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1,the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function.Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses.Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea.The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI.Interestingly,the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation,a hallmark of functional GI disorders.Moreover,the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus,suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract,further indicating fecal-oral transmission as another important route of viral spread.This review summarized the evidence for pathophysiological mechanisms(impaired barrier function,gut inflammation,altered serotonin metabolism and gut microbiota dysbiosis)underlying the GI symptoms in patients with COVID-19.

Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs

The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million worldwide.Aging,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelial functions predispose to COVID-19.While respiratory epithelium is the main route of virus entry,the endothelial cells(ECs)lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients.COVID-19 not only affects the lungs and respiratory system but also gastrointestinal(GI)tract,liver,pancreas,kidneys,heart,brain,and skin.Blood vessels are likely conduits for the virus dissemination to these distant organs.Importantly,ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network.The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract,liver,pancreas,etc.,however,the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury,spreading to various organs,and injury healing have not been sufficiently emphasized.In the present article,we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic,significant efficacy in controlling severe COVID-19 infection.

Event-related potential N170 for early diagnosis of face recognition impairment in Parkinson's disease

Event-related potential （ERP） studies of cognitive function in Parkinson＇s disease （PD） have focused on P300 and N270. However, little is known regarding face recognition ERP in PD. The present study assessed cognitive function in PD patients using neuropsychological scales and analyzed N170 of visuospatial function impairment （VFI） in PD. Results showed that Montreal cognitive assessment can be used for assessing cognitive impairment when visuospatial functioning is changed during the early stage of PD. Face recognition has clinical significance for detecting changes in visuospatial functioning. However, N170 is not sensitive for detection of VFI in PD, which implies that VFI does not appear in the stage of structure coding in face recognition. In addition, VFI affects face recognition.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

The Association between Pulmonary Function Impairment and Colon Inflammation in Ulcerative Colitis Patients： A Scientific Basis for Exterior-Interior Correlation between Lung and Large Intestine

Objective： To investigate the involvement of pulmonary function impairment in ulcerative colitis（UC）, and explore a scientific basis for the Chinese medicine（CM） theory of exterior-interior correlation between Lung（Fei） and Large intestine（Dachang）. Methods： Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein（CRP） and erythrocyte sedimentation rate（ESR） concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph（CXR）. Results： Pulmonary function abnormalities were present in 72 of 120 patients. The median（interquartile range） vital capacity（VC）, forced vital capacity（FVC）, forced expiratory volume in 1 s（FEV_1）, carbon monoxide diffusion capacity（DL_∞） of lung, total lung capacity（TLC） and functional residual volume（FRV） were decreased in distal UC and pancolitis compared with ulcerative prochitis（P〈0.0005）. Male patients had increased VC, FEV_1/FVC, and residual volume（RV）/TLC compared with female（P〈0.0005）, but decreased DLCO and carbon monoxide iffusion capacity（KCO） of lung/alveolar ventilation（P〈0.0005）. Age was strongly correlated with RV（Spearman rank correlation coefficient（rs）=–0.57, P〈0.0001）, and RV/TLC（rs=0.48, P〈0.0001）. Age was also correlated with FEV_1/FVC（rs=–0.29, P=0.001）, forced expiratory flow in 75% vital capacity（FEF75%, rs=–0.20, P=0.03）, DLCO（rs=–0.21, P=0.02）, TLC（rs=–0.25, P=0.006）, and FRV（rs=–0.28, P=0.002）. The course of disease was correlated with FEF75%（rs=–0.18, P=0.049） and KCO（rs=–0.19, P=0.036）. Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. Conclusions： Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine.

How to reduce bacillus Calmette-Guerin discontinuation in patients with severe functional impairment

Background:Severe functional impairment is often considered a contraindication to intravesical therapy for nonmuscle-invasive bladder cancer(NMIBC).A tailored intravesical bacillus Calmette-Guérin(BCG)procedure was evaluated in high-risk(HR)-NMIBC patients with severe functional impairment.Materials and methods:Patients with a Katz Index score of 2 or less and an initial diagnosis of HR-NMIBC with atraumatic insertion of a Foley-type indwelling catheter,bladder emptying,and BCG instillation were prospectively treated;after 2 hours,the bladder was emptied and the catheter was removed(group A).After propensity score matching,52 patients in group A were compared with that of 52 consecutive patients in group B using a retrospective database,with similar baseline/oncological characteristics and treated with standard intermittent catheterization.Moreover,groups A and B were compared with that of 130 consecutive patients(group C)retrospectively evaluated,with similar oncological characteristics but with a Katz Index score of 3 or greater and treated with standard intermittent catheterization.Results:The discontinuation rates were 11.5%,35%,and 9%in groups A,B,and C,respectively(A vs.B,log-rank score 42.52[po<0.05];B vs.C,107.6[p<0.05];A vs.C,3.45[p>0.05]).The overall adverse event rates were 38.5%,57.7%,and 39.2%,respectively(A vs.B,p=0.04;B vs.C,0.03;A vs.C,0.92).The rates of severe adverse events were 1.9%,1.9%,and 1.5%,respectively,without statistically significant differences.The cumulative HR disease-free survival rates were 63.4%,48%,and 69.2%,respectively(A vs.B,log-rank score 154.9[p<0.05];B vs.C,415[p<0.05];A vs.C,244[p<0.05]).Conclusions:A tailored intravesical instillation procedure may reduce BCG discontinuation and adverse effects.

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment（a MCI） to Alzheimer＇s disease（AD）. As a part of the medial temporal lobe memory system,the hippocampus is one of the brain regions affected earliest by AD neuropathology,and shows progressive degeneration as a MCI progresses to AD. Currently,no validated biomarkers can precisely predict the conversion from a MCI to AD. Therefore,there is a great need of sensitive tools for the early detection of AD progression. In this review,we summarize the specifi c structural and functional changes in the hippocampus from recent a MCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile,this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of a MCI to AD.