Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

OBJECTIVE To investigate the clinical efficacy and safety of Zhengxintai granules as in the treatment of microvascular angina （MVA） following percutaneous coronary intervention （PCI） in patients with acute ST-segment elevation myocardial infarction （STEMI） and qi deficiency and blood stasis syndrome. METHODS Patients with STEMI and qi deficiency and blood stasis syndrome who underwent PCI and developed MVA and were admitted to the Jinan Fourth People’s Hospital （Jinan Cardiovascular Hospital） from March 2022 to March 2025 were selected， they were randomly divided into the control group and the observation group according to a random number table， with 76 cases in each group. Patients in the control group received conventional Western medicine treatment combined with a placebo， while patients in the observation group received Zhengxintai granules （5 mg per dose， three times daily， for 8 weeks） in addition to conventional Western medicine treatment. The clinical efficacy [including the total effective rate of traditional Chinese medicine （TCM） syndrome improvement and the total effective rates of Western clinical efficacy] was compared between the two groups. The following indicators were detected before and after treatment： TCM syndrome scores， angina pectoris episodes [daily attack frequency， duration per attack， Visual Analogue Scale （VAS） score]， cardiac function indicators [lactate dehydrogenase （LDH）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， left ventricular end-diastolic dimension （LVEDD）， left ventricular end-systolic dimension （LVESD）， left ventricular ejection fraction （LVEF）， cardiac output （CO）， fractional shortening （FS）]， coagulation function indicators [thrombin time （TT）， prothrombin time （PT）， fibrinogen （FIB）]， fibrinolytic marker （D-dimer）， vascular endothelial function indicators [vascular endothelial growth factor （VEGF）， nitric oxide （NO）， endothelin-1 （ET-1）] and myocardial microcirculation hemodynamic indicators [end-diastolic velocity （EDV）， peak systolic velocity （PSV）， resistance index （RI）， pulsatility index （PI）]. The quality of life [Seattle Angina Questionnaire （SAQ） score] and the incidence of adverse reactions were also compared between the two groups. RESULTS There was no patient dropout during the entire course of the study. The total effective rates of improvement in TCM syndromes and the total effective rates of Western clinical efficacy in the observation group were significantly higher than those in the control group （93.42% vs. 82.89%， 94.74% vs. 84.21%， P＜0.05）. Before the treatment， the comparison of each examination indicator between the two groups showed no statistically significant differences （P＞0.05）. Compared with before treatment， the TCM syndrome scores， the number of daily angina pectoris attacks and the duration of each attack， the VAS scores， LDH， NT-proBNP， FIB， D-dimer， ET-1 levels， LVEDD， LVESD， RI and PI after treatment in both groups were significantly reduced， shortened or decreased （P＜0.05）； VEGF and NO levels， LVEF， CO， FS， TT， PT， EDV， PSV， and the standard scores of five dimensions including angina pectoris stability， as well as the total scores of SAQ， all significantly increased or prolonged （P＜0.05）. Furthermore， the improvements in the aforementioned indicators （except for LVEF） in the observation group were significantly greater than those in the control group （P＜0.05）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Zhengxintai granules， when used as an adjunct to conventional Western medicine， can significantly alleviate the related symptoms of MVA in STEMI patients with qi deficiency and blood stasis syndrome after PCI， repair damaged cardiac function， restore the balance of the coagulation-fibrinolysis system， improve vascular endothelial function and myocardial microcirculation perfusion， and significantly enhance the quality of life of patients

Hemoglobin, the principal protein in red blood cells, is crucial for oxygen transport in the bloodstream. The quantification of hemoglobin concentration is indispensable in medical diagnostics and health management, which encompass the diagnosis of anemia and the screening of various blood disorders. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy. Consequently, it is necessary to develop hemoglobin-specific antibodies characterized by high specificity and affinity to enhance detection accuracy. In this study, we immunized a Bactrian camel (Camelus bactrianus) with human hemoglobin and subsequently constructed a nanobody library. Utilizing a solid-phase screening method, we selected nanobodies and evaluated the binding activity of the screened nanobodies to hemoglobin. Initially, human hemoglobin was used to immunize a Bactrian camel. Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated. Subsequently, ten hemoglobin-specific nanobody sequences were identified through three rounds of adsorption-elution-enrichment assays, and these nanobodies were subjected to eukaryotic expression. Finally, enzyme-linked immunosorbent assay and biolayer interferometry were employed to evaluate the stability, binding activity, and specificity of these nanobodies. The results demonstrated that the nanobodies maintained robust binding activity within the temperature range of 20-40 ℃ and exhibited the highest binding activity at pH 7.0. Furthermore, the nanobodies were capable of tolerating a 10% methanol solution. Notably, among the nanobodies tested, VHH-12 displayed the highest binding activity to hemoglobin, with a half maximal effective concentration (EC₅₀) of 10.63 nmol/L and a equilibrium dissociation constant (K_D) of 2.94×10^-7 mol/L. VHH-12 exhibited no cross-reactivity with a panel of eight proteins, such as ovalbumin and bovine serum albumin, while demonstrating partial cross-reactivity with hemoglobin derived from porcine, goat, rabbit, and bovine sources. In this study, a hemoglobin-specific high-affinity nanobody was successfully isolated, demonstrating potential applications in disease diagnosis and health monitoring.
Animals ; Camelus/immunology* ; Single-Domain Antibodies/immunology* ; Hemoglobins/immunology* ; Humans ; Peptide Library

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Objective:To analyze the correlation between the skin temperature variation trajectory in the radiation field and the occurrence of grade 2 or higher radiation dermatitis in female breast cancer patients during postoperative radiotherapy.Methods:This prospective cohort study used convenience sampling to select 103 breast cancer patients who underwent modified radical mastectomy and subsequent radiotherapy at the Fourth Hospital of Hebei Medical University from May 2022 to December 2022. All patients received three-dimensional conformal radiotherapy (3D-CRT), with an irradiation field covering the chest wall ± supraclavicular and infraclavicular lymphatic drainage regions, and a prescribed dose of 50 Gy delivered in 25 fractions. Skin temperature in the irradiated area was measured using an infrared thermometer before radiotherapy and on the days of the 5 th, 10 th, 15 th, 20 th, and 25 th fractions. The latent classes of skin temperature variation trajectories were identified using the Mplus latent class growth model, and logistic regression was applied to analyze the correlation between the skin temperature variation trajectory and the occurrence of grade 2 or higher radiation dermatitis. Results:The skin temperature variation trajectories in the irradiated field of breast cancer patients undergoing postoperative radiotherapy could be divided into two groups: the temperature non-increasing group (81/103) and the temperature increasing group (22/103). The Akaike information criterion (AIC) was 66.468, the Bayesian information criterion (BIC) was 116.528, and the entropy was 0.810, with a likelihood ratio test P-value of 0.037, and a Bootstrap-based likelihood ratio test P-value<0.001. After adjusting for covariates such as age and body mass index, logistic regression analysis showed that the risk of developing grade 2 or higher radiation dermatitis in the temperature increasing group was 6.92 times of that in the temperature non-increasing group ( OR=6.92, 95% CI = 2.30-20.82, P=0.001). Conclusions:There is group heterogeneity in the skin temperature variation trajectories of breast cancer patients undergoing radiotherapy, and patients with a rise in skin temperature have a higher risk of developing grade 2 or higher acute radiation dermatitis.

Objective To observe the characteristics of affected shoulder joint range of motion in patients with breast cancer after ax-illary lymph node dissection before radiotherapy.Methods From January,2022 to December,2023,185 female patients from the Fourth Hospital of Hebei Medical Uni-versity after unilateral breast cancer who underwent axillary lymph node dissection were reviewed.Their general data were collected;affected shoulder joint range of motion was evaluated by progoniometer;lymphedema of af-fected upper extremities was evaluated by water volume replacement;Verbal Rating Scale(VRS)was used to evaluate the pain in the upper extremity of the operative side.Results The angles of anterior flexion and abduction of the affected shoulder joint were(158.90±17.17)° and(147.70±24.59)°.There were significant differences in the angles of affected shoulder anterior flexion and abduction among patients at different ages(more than 55 years and less than 55 years)and those with or without lymphede-ma.Multiple linear regression showed that the angle of affected shoulder flexion was smaller in patients aged more than 55 years(β=-7.766,95%CI-13.161 to-2.360,P=0.005),and with lymphedema(β=-10.991,95%CI-19.063 to-2.925,P=0.008);was larger in patients with longer duration after operation(β=0.463,95%CI 0.012 to 0.924,P=0.049),and BMI 24 to 27.9 kg/m2(β=6.211,95%CI 0.660 to 11.761,P=0.030)(compared with BMI<24 kg/m2).The angle of affected shoulder abduction was smaller in patients aged more than 55 years(β=-10.047,95%CI-17.358 to-2.747,P=0.008),and with lymphedema(β=-14.171,95%CI-25.191 to-3.150,P=0.013).Conclusion Shoulder joint range of motion has reduced in flexion and abduction in patients at early stage after axillary lymph node dissection for breast cancer,which is related to age and lymphedema.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To investigate the current practice of nasogastric tube care and the training needs among nurses in the emergency departments of tertiary hospitals in Beijing, to provide a basis for further standardizing nasogastric tube care practices.Methods:A convenience sampling method was used to select head nurses and nurses from the emergency departments of 47 tertiary hospitals in Beijing in June 2024. A self-designed questionnaire on the current practice of nasogastric tube care and training needs was administered to the participants.Results:A total of 47 emergency departments from tertiary hospitals in Beijing were surveyed, of which only 25 departments implemented nasogastric tube techniques. In the key practices of nasogastric tube care, nine hospitals met the overall implementation standards, while 16 hospitals had substandard implementation. The key practices with poor standardization included the frequency of changing the nasogastric tube dressing, blind insertion (spiral nasogastric tube) through the pylorus, the recommended temperature for enteral nutrition liquids, and the timing for flushing the nasogastric tube. There were statistically significant differences ( P<0.05) in the presence of specialized nasogastric tube care teams and the use of case discussions or workshops for department training between hospitals with good and poor implementation. Moreover, 89.5% (496/554) of the nurses indicated a need for training related to nasogastric tube maintenance, and 91.9% (509/554) expressed willingness to participate in technical training or seminars. Statistically significant differences ( P<0.05) were found between emergency specialized nurses and non-specialized nurses in terms of preferred training frequency, duration, format, and content (sharing of the latest research and advancements) . Conclusions:Nasogastric tube techniques have not been widely implemented in the emergency departments of tertiary hospitals in Beijing. The standardization of nasogastric tube care needs further improvement, and there is a significant demand for training among emergency nurses, indicating an urgent need for specialized nasogastric tube training programs.