Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis and hepatocellular carcinoma, but its pathogenesis has not been fully elucidated. Mutations in the HBV preS/S genes can lead to impaired secretion of either HBsAg or S-protein resulting in the accumulation of defective viruses or S protein in cells. In our previous work, the M133S mutation was present in the HBV S gene of maintenance hemodialysis (MHD) patients with OBI. In this study, we investigated the potential role of amino acid substitutions in S proteins in S protein production and secretion through the construction of mutant S gene plasmids, structural prediction, transcriptome sequencing analysis, and in vitro functional studies. Protein structure prediction showed that the S protein M133S mutant exhibited hydrophilic modifications, with greater aggregation and accumulation of the entire structure within the membrane phospholipid bilayer. Differential gene enrichment analysis of transcriptome sequencing data showed that differentially expressed genes were mainly concentrated in protein processing in the endoplasmic reticulum (ER). The expression of heat shock family proteins and ER chaperone molecules was significantly increased in the wild-type and mutant groups, whereas the expression of mitochondria-associated proteins was decreased. Immunofluorescence staining and protein blotting showed that the endoplasmic reticulum-associated protein PDI, the autophagy marker LC3, and the lysosome-associated protein LAMP2 co-localized with the S proteins in the wild-type and mutant strains, and their expression was increased. The mitochondria-associated TOMM20 protein was also co-expressed with the S protein, but expression was significantly reduced in the mutant. The M133S mutation in the S gene is expressed as a defective and misfolded protein that accumulates in the endoplasmic reticulum causing secretion-impaired endoplasmic reticulum stress, which in turn triggers mitochondrial autophagy and recruits lysosomes to fuse with the autophagosome, leading to mitochondrial clearance. This study preliminarily demonstrated that the mutation of M133S in the S gene can cause OBI and is associated with disease progression, providing a theoretical basis for the diagnosis and treatment of OBI.

BACKGROUND: The clinical manifestations and prognosis of hemodialysis patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during the Omicron wave of the pandemic infection were still unclear. This study investigated the clinical characteristics of patients undergoing maintenance hemodialysis (MHD) infected with it.
METHODS: This retrospective single-center study included 151 patients undergoing MHD. Healthcare workers were selected as control group were assessed from December 1, 2022 to March 31, 2023. Clinical data, laboratory test results, treatment protocols, and prognoses were collected and analyzed.
RESULTS: The study population included 146 patients with MHD, 93 (63.7%) of whom were infected with SARS-CoV-2. The number of non-severe, severe, and critical cases was 84 (90.3%), 4 (4.3%), and 5 (5.3%), respectively. Six patients (6.5%) died during the study period. The main symptoms of SARS-CoV-2 infection, including fever, cough, and fatigue, were less common in patients with MHD than the controls. During SARS-CoV-2 infection, the C-reactive protein (2.9 vs. 11.8 mg/dl, p < 0.0001) and ferritin levels(257.7 vs. 537 ng/l, p < 0.0001) were elevated. The hemoglobin(113vs 111 g/L, p = 0.0001) and albumin levels(39.4 vs. 36.1 g/L, p < 0.0001) decreased. Generally, it took two months for the hemoglobin levels to recover. Positivity rate for SARS-COV-2 serum immunoglobin G (IgG) antibodies and IgG titers were lower in dialysis patients than the controls. Age was positively associated with disease severity, while age and hyponatremia were associated with death.
CONCLUSIONS: Patients with MHD and COVID-19 were primarily classified as non-severe. SARS-CoV-2 infection would soon lead to the increase of inflammation related acute response protein in dialysis patients, and then lead to the decrease of hemoglobin and albumin. About 9.6% in HD patients were severe cases and had poor prognosis. Advanced age and hyponatremia were associated with disease severity and prognosis.

BACKGROUND: In hemodialysis (HD) patients, anemia is greatly improved due to regular weekly use of iron and erythropoietin (EPO), but a large number of patients still show persistent anemia. We do a survey to elucidate the influencing factors that contribute to the failure of hemoglobin (Hb) to meet the standard and provide epidemiological data reference for promoting the recognition of renal anemia and improving the treatment effect of renal anemia.
METHODS: The clinical data of End-Stage Renal Disease (ESRD) HD patients in 22 tertiary hospital HD centers in Liaoning Province from September 2021 to June 2022 were collected by convenient sampling. According to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) anemia diagnostic criteria. The standard of Hb compliance: Hb ≥110 g/L is considered as Hb compliant, and Hb <110 g/L as Hb non-compliant. The factors influencing Hb up-to-standard in ESRD HD patients and their correlations were analyzed by comparison between the two groups.
RESULTS: The results of this study showed that among the 1,652 ESRD patients investigated in Liaoning Province, the prevalence rate of anemia was 89.29% (1,475/1,652), and the Hb compliance rate was 46.25% (764/1,652). The Hb compliance rate in maintenance hemodialysis (MHD) patients with different primary diseases was statistically significant (P<0.05). Compared with the Hb non-standard group, the gender, dialysis access, HD frequency, concurrent infection, primary disease of ESRD patients, red blood cell (RBC) count, hematocrit (HCT), mean RBC Hb concentration, mean RBC Hb content, platelet (PLT), albumin (ALB), total protein (TP), serum creatinine (Cr), serum calcium (Ca), serum potassium (K), ferritin (Fer), serum iron (SI), and transferrin (TRE) saturation were significantly different between both groups (P<0.05). Adrenaline was an independent risk factor affecting Hb failure in ESRD patients (OR =1.001, 95% CI: 1.000-1.002); dialysis frequency (OR =0.726, 95% CI: 0.601-0.878), ALB (OR =0.959, 95% CI: 0.929-0.990), TP (OR =0.982, 95% CI: 0.968-0.996), serum Cr (OR =0.959, 95% CI: 0.929-0.999), and SI (OR =0.961, 95% CI: 0.940-0.982) were protective factors affecting Hb failure in ESRD patients (P<0.05). Pearson correlation analysis showed that ALB, TP, serum Cr, serum Ca, serum K, SI, and TRE saturation were positively correlated with Hb (P<0.05).
CONCLUSIONS: The anemia rate of ESRD patients treated with MHD in Liaoning Province is high. Based on the results, increasing the frequency of dialysis can improve anemia. Parathyroid hormone levels need to be controlled.

UNASSIGNED: Catheter-Related Blood Stream Infection (CRBSI) is the major limitation of using Tunneled cuffed catheter (TCC) for long-term Hemodialysis. The standard therapy of CRBSI involves systemic antibiotics with catheter replacement/removal. As antibiotic alone is rarely effective therapy for CRBSI, biofilm eradication using antimicrobial locking solutions is a promising modality for CRBSI treatment, hence catheter salvage. The present study evaluated the efficacy and safety of Ethanol-lock therapy (ELT) in combination with systemic antibiotics for the management of CRBSI associated with hemodialysis TCC.
UNASSIGNED: 56 patients with CRBSI were treated with 70% ELT (1 h daily for 5 days) along with systemic antibiotics. Seventeen patients with CRBSI who didn\'t consent to ELT were treated with antibiotics alone. The effect of ELT was evaluated as clinical cure (fever resolution and negative surveillance cultures), infection-free TCC survival duration and adverse events of ELT among patients with CRBSI. The parameters were compared with 17 patients treated with antibiotics alone.
UNASSIGNED: ELT was successful in 50 out of 56 patients (89.28%); compared to 41.17% (seven out of 17) with antibiotics alone (p < 0.001). Mean TCC survival was also significantly higher with ELT combined with systemic antibiotics (126.23 ± 18.67 days) compared to antibiotics alone (38.76 ± 9.91) (p = 0.006). No systemic adverse effects were noted with ELT; two patients receiving ELT had catheter breakage during the study period.
UNASSIGNED: We conclude that short-dwell daily ELT with systemic antibiotics is an effective therapy for CRBSI in hemodialysis patients with TCC.

To observe the effects and safety of Sacubitril/Valsartan (SV) on heart function and blood pressure in maintenance hemodialysis (MHD) patients with chronic heart failure (CHF). The clinical data and biochemical parameters of MHD patients were retrospectively analyzed. These MHD patients, who were collected from January 2020 to June 2021 in the Blood Purification Center of the First Affiliated Hospital of Chongqing Medical University, received SV treatment to control heart failure (HF). Altogether 54 MHD patients complicated with CHF who received SV treatment were selected for this self-controlled study. The changes of serum biochemical indexes, left anteroposterior atrial diameter (LAD), left ventricular end diastolic diameter (LVID), left ventricular ejection fraction (LVEF), right atrial transverse diameter (RAD), right anteroposterior ventricular diameter (RVD), blood pressure and antihypertensive drug dosage before and after treatment were assessed. The adverse reactions such as hyperkalemia, hypotension before dialysis, angina pectoris, myocardial infarction, cerebral infarction, cerebral hemorrhage and hospitalization due to HF were recorded before and after treatment. After treatment, LAD and LVID, incidence of angina pectoris, duration of hospitalization for HF, systolic blood pressure and diastolic blood pressure before dialysis, and the calibration value of antihypertensive drugs were all reduced, while LVEF was increased. The incidence of hyperkalemia (serum potassium >5.5 mmol/L) also increased after treatment compared with before treatment (P<0.05). The incidence of hypotension, angina pectoris, myocardial infarction, cerebral infarction and cerebral hemorrhage during treatment was similar to that before treatment (P>0.05). SV can effectively improve left atrial and left ventricular remodeling in MHD patients with CHF, improve LVEF, reduce the incidence of angina pectoris and duration of hospitalization due to HF in MHD patients, which is conducive to the control of blood pressure in MHD patients with hypertension. The incidence of hyperkalemia increased during SV treatment. SV did not increase the incidence of hypotension, myocardial infarction, cerebral infarction, cerebral hemorrhage and other events in MHD patients.

This cross-sectional study aimed to investigate the relationship between abdominal aortic calcification (AAC), which is a marker of vascular calcification, and volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) in maintenance hemodialysis (MHD) patients.
All participants underwent lumbar vertebral vBMD measurement by QCT. Eight cross-sections were extracted sequentially and analyzed by ImageJ software to obtain the ratio of the calcified area to the abdominal aortic area (the calcification ratio). The AAC score was determined by the sum of the calcification ratios. The relationship between AAC and vBMD was analyzed using multivariate logistic regression.
Ninety MHD patients (58.89% male) with a mean age of 63.43 (standard deviation [SD] = 13.20) years were included in the study. AAC was present (AAC score > 0) in 93.33% of the patients. The 75th percentile of the AAC score corresponding to 119 was used as the cutoff point between the mild and severe groups. After full adjustment in the logistic model, AAC was found to be inversely associated with vBMD (odds ratio [OR], 0.970; 95% confidence interval [CI], 0.944 to 0.996; P = 0.025), and patients with osteoporosis had a significantly higher risk of severe AAC than those with normal bone mass (OR, 14.498; 95% CI, 1.507 to 139.486; P = 0.021). The independent inverse association was still stable after adjusting for variables measured at different time periods and using different cutoff points of the AAC score.
There was an independent inverse association between AAC and vBMD, and osteoporosis was significantly associated with severe AAC in patients with MHD.

Although greater dietary intake of protein has been associated with beneficial health effects among patients receiving maintenance hemodialysis (MHD), the effects of plant protein intake are less certain. We studied the association of the proportion of protein intake derived from plant sources with the risk of mortality among patients receiving MHD and explored factors that may modify these associations.
Prospective observational cohort study.
1,119 Chinese hemodialysis patients aged over 18 years receiving MHD in 2014-2015.
The proportion of plant protein intake to total protein intake.
All-cause mortality and cardiovascular disease (CVD) mortality.
Segmented regression models were fit to examine the association of plant protein intake proportion with the risk of all-cause mortality and CVD mortality. Multivariable-adjusted Cox proportional and cause-specific hazards models were used to estimate the hazard ratios (HR) and 95% CI for these outcomes.
The means of plant protein intake normalized to ideal body weight and plant protein intake proportion were 0.6±0.2 (SD) g/kg per day and 0.538±0.134, respectively. During a median follow-up period of 28.0 months, 249 deaths occurred, with 146 of these deaths resulting from CVD. Overall, there was a U-shaped association between plant protein intake proportion and the risk of all-cause mortality, with an inflection point at 45%. Among patients with a plant protein intake proportion<45%, there was a 17% lower rate of mortality with each 5% greater plant protein intake proportion (HR, 0.83 [95% CI, 0.73-0.96]). Among patients with plant protein intake proportion≥45%, there was a 9% greater rate of mortality with each 5% greater plant protein intake proportion. A similar U-shaped association was observed for CVD mortality, with an inflection point at 44%.
Observational study, potential unmeasured confounding.
There was a U-shaped association between plant protein intake proportion and the risk of all-cause and cardiovascular mortality in MHD patients. If confirmed, these findings suggest a potential avenue to improve outcomes in this patient population.

BACKGROUND: Intradialytic hypotension (IDH) remains the most frequent severe side effect of hemodialysis (HD) and increases patient morbidity and mortality. Excessive ultrafiltration (UF) is considered the leading cause of IDH. This study developed a suitable prescription of UF to reduce the incidences of IDH episodes.
METHODS: A retrospective study was performed to analyze 33,224 HD/hemodiafiltration (HDF) treatments in 312 patients. The prescription of UF were determined following the International Society of Peritoneal Dialysis (ISPD) guideline. The Pearson\'s method was used to study the correlation between relative variables. The receiver operating characteristic (ROC) curve was used to predict the value of the UF/weight ratio (UF/Wt) for IDH in all patients to establish a diagnostic cut-off point. Univariate and multivariate logistic regression analyses were applied to study the risk factors of IDH.
RESULTS: Twelve thousand five hundred and fifty-eight sessions of IDH (38.7%) were identified, among which 1,224 (3.6%) were recorded with intervention against IDH. Both the systolic blood pressure (SBP) and mean arterial pressure (MAP) of the hemodialytic patients were positively correlated with the UF quantity and the UF/Wt, but negatively correlated with blood flow. The ROC curve showed that UF/Wt =0.04 was the cut-off point for IDH. Age [per 10-year increment, odds ratio (OR) =1.005, 95% confidence interval (CI): 1.004 to 1.007, P=0.000], diabetes mellitus (OR =1.209, 95% CI: 1.122 to 1.303, P=0.000), and UF/Wt >0.04 (OR =1.605, 95% CI: 1.532 to 1.682, P=0.000) were all independently associated with higher incidences of IDH.
CONCLUSIONS: IDH commonly occurs during HD in Chinese patients. Unchangeable factors such as diabetes and age, and modifiable factors including UF were associated with IDH. A UF/Wt threshold more than 0.04 may be a potential alert for avoiding IDH, especially in the elderly and diabetic patients.

BACKGROUND: Quarantine is an effective measure to contain the spread of infectious disease, however, it can be a great challenge for patients undergoing maintenance hemodialysis (MHD). The purpose of this study was to evaluate the impact of hospital-based group medical quarantine (H-GMQ) on blood pressure (BP) in MHD patients, and the effect of age on change in BP.
METHODS: MHD patients in our dialysis center who were under H-GMQ due to exposure to coronavirus disease 2019 (COVID-19) were enrolled. Their demographic data, clinical characteristics, and laboratory data were collected from 3 months before H-GMQ to the end of H-GMQ. They were divided into two groups by median age (61 y). BP and related data before and during H-GMQ between groups were analyzed. The association between age and change in BP was estimated using multivariable linear regression analysis.
RESULTS: One hundred and thirty MHD patients were enrolled. The pre-dialysis systolic BP (SBP) and heart rate (HR) during H-GMQ were significantly higher than before, the serum sodium decreased significantly at the end of H-GMQ. After adjusting for covariates by multivariable regression, age had a negative correlation with BP elevation (R2 =0.218, P=0.246). Subgroup analysis showed that both pre-dialysis SBP and diastolic BP (DBP) increased significantly during H-GMQ in patients less than 61 years old, instead, neither SBP nor DBP changed in the elderly.
CONCLUSIONS: H-GMQ increased the pre-dialysis BP in MHD patients, especially in younger patients. More attention should be paid to these patients\' BP if another quarantine is needed.

BACKGROUND: Cardiovascular disease (CVD) is the most common adverse event of maintenance hemodialysis (MHD), in which serum soluble klotho plays a vital role. Tanshinone IIA (tan) has been used to protect the cardiovascular system for hundreds of years. This study was performed to investigate the effects of tan on klotho level and cardiovascular events of MHD patients.
METHODS: Totally 112 patients were enrolled in this study, and their demographic, clinical, and laboratory characteristics were collected at admission. Serum soluble klotho, carotid intima-media thickness (CIMT), and abdominal aorta calcification (AAC) level were measured to determine their relationship. Seventy-one patients were given sodium tan sulfonate injection according to their willingness, while 41 patients were not given any specific treatment. The endpoint events were recorded, including cardiovascular mortality, nonfatal cardiovascular events, and all-cause mortality.
RESULTS: All patients were divided into two groups on whether the level of serum soluble klotho was more than medium or not. CIMT and AAC grade showed significant differences between 2 groups (group of low level of klotho versus group of high level of klotho, CIMT: 1.03±0.22 vs. 0.85±0.20 mm, P<0.001; AAC grade: 5.04±3.93 vs. 1.69±2.30 points, P<0.001). All patients were followed up for at least one year. The results revealed that using tan improved the level of serum soluble klotho (490.23±153.97 pg/mL after using tan versus 444.49±143.32 pg/mL before using tan, P=0.042). Kaplan-Meier curves showed that cardiovascular event-free survival was significantly higher in patients given tan (P=0.040) compared with patients not given tan.
CONCLUSIONS: Tan effectively increases the level of serum soluble klotho and further reduces the incidence of cardiovascular events in MHD patients.