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.

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.

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.