Hepatitis B virus （HBV） infection is a global public health issue， affecting the health of 250 million people worldwide. Despite the significant progress in antiviral therapy for HBV， some patients still experience low-level viremia （LLV） after receiving antiviral therapy and fail to achieve viral clearance， with an HBV DNA load remaining at a relatively low level of 20 — 2 000 IU/mL. LLV is often caused by multiple factors such as the high stability of the virus， the difficulty in clearing the virus with antiviral drugs， host immune factors， and drug resistance， which increase the difficulties in antiviral therapy. In addition， LLV can also cause liver damage， which may eventually progress to severe outcomes such as hepatocellular carcinoma. This article reviews LLV in hepatitis B in terms of diagnosis， influencing factors， clinical significance， and treatment strategies.

Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
Collagen/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Tissue Engineering/methods* ; Animals ; Biocompatible Materials/chemistry*

Objective To evaluate the risk of bias and reporting quality in randomized controlled trials(RCTs)of the Chinese medicine injection for acute cerebral infarction in the last five years.Methods RCTs literature on Chinese medicine injection in the treatment of acute cerebral infarction was systematically searched in CNKI,Wanfang Data,VIP,China Biology Medicine Database(CBM),PubMed,Embase and Cochrane Library from April 20,2018 to April 20,2023.The risk of bias and reporting quality of included RCTs were evaluated using the Cochrane Risk of Bias Tool(ROB 1.0)and CONSORT-CHM Formulas 2017,respectively.Results A total of 4 301 articles were retrieved,and 408 RCTs were included according to inclusion and exclusion criteria.The ROB evaluation results showed that the the majority of studies were rated as having an unclear risk of bias due to the lack of reporting on allocation concealment,blind method,trial registration information,and funding sources.The evaluation results of CONSORT-CHM Formulas 2017 showed that the number of reported papers of 17 items was greater than or equal to 50%,and the number of reported papers of 25 items was less than 10%,and most of the RCTs did not show the characteristics of TCM syndrome differentiation and treatment.Conclusion The quality of Chinese medicine injection in the treatment of acute cerebral infarction RCTs is generally low.It is recommended that researchers refer to the methodology design of RCTs and international reporting standards,improve the trial design,standardize the trial report,and highlight the characteristics of TCM syndrome differentiation and treatment.

Objective:To explore the risk factors related to delayed pleural effusion in multiple trauma patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 145 multiple trauma patients admitted to the First Affiliated Hospital of Soochow University from January 2022 to October 2023, including 99 males and 46 females, aged 18-81 years [56.0(46.5, 64.5)years]. Based on whether delayed pleural effusion developed after injury, the patients were divided into delayed pleural effusion group ( n=66) and non-delayed pleural effusion group ( n=79). The clinical data of the patients in both groups were collected, including gender, age, underlying disease (diabetes mellitus and hypertension), cause of injury (traffic injury, blow injury, fall from height, and others), comorbid injuries (traumatic brain injury, maxillofacial fracture, clavicular fracture, scapular fracture, sternal fracture, spinal fracture, multiple rib fracture, pneumothorax, lung contusion, and pelvic fracture), severity of injury [injury severity score (ISS) and abbreviated injury scale (AIS) score for the chest], location and number of rib fractures, vital signs at admission (body temperature, heart rate, respiration, systolic blood pressure, diastolic blood pressure), and clinical test indices [white blood cells (WBC), hemoglobin (Hb), platelets (PLT), total protein (TP), albumin (ALB), C-reactive protein (CRP), procalcitonin (PCT), fibrinogen (FIB), fibrin degradation product (FDP), D-dimer (D-D), aspartate transaminase (AST), alanine transferase (ALT), and creatinine (Cr)]. Univariate analysis was conducted to assess the correlation between the forementioned factors and the development of delayed pleural effusion after multiple traumas. Multivariate Logistic regression analysis was used to determine the independent risk factors for the development of delayed pleural effusion after multiple traumas. Results:The results of univariate analysis showed that multiple rib fracture, pneumothorax, pulmonary contusion, chest AIS score, posterior rib fracture, number of rib fractures, TP, ALB, CRP, PCT and FDP were correlated with delayed pleural effusion in multiple trauma patients ( P<0.05 or 0.01); whereas gender, age, underlying disease, cause of injury, sternal fracture, spinal fracture, clavicular fracture, scapular fracture, pelvic fracture, maxillofacial fracture, traumatic brain injury, anterior rib fracture, ISS, vital signs at admission, WBC, Hb, PLT, FIB, D-D, AST, ALT, and Cr were not correlated with delayed pleural effusion in multiple trauma patients ( P>0.05). The results of multivariate Logistic regression analysis revealed that lung contusion ( OR=3.96, 95% CI 1.59, 9.85, P<0.01), ALB ( OR=0.79, 95% CI 0.66, 0.94, P<0.01), and CRP ( OR=1.02, 95% CI 1.01, 1.03, P<0.01) were significantly correlated with delayed pleural effusion in multiple trauma patients. Conclusion:Lung contusion, ALB, and CRP are the independent risk factors for delayed pleural effusion in multiple trauma patients.

Objective:To explore the effect of progressive case teaching based on Omaha system in standardized training for new nurses.Methods:Using convenience sampling method, 58 new nurses from Yantai Affiliated Hospital of Binzhou Medical University from January to December 2021 were selected as control group, and 58 new nurses from January to December 2022 were selected as experimental group. Experimental group received progressive case teaching based on Omaha system, while control group received routine standardized training. Both groups received training for six months. After six months of training, the academic performance, clinical thinking ability, and satisfaction of the two groups were compared.Results:After intervention, experimental group scored higher in various dimensions of academic performance and clinical thinking ability, as well as satisfaction scores with the teacher, teaching methods, and teaching effectiveness, compared to the control group, with statistical differences ( P<0.05) . Conclusions:The progressive case teaching based on Omaha system in standardized training for new nurses can improve academic performance, enhance clinical thinking abilities, and gain recognition from new nurses.

The identification of clinical questions for clinical practice guidelines of Chinese patent medicine （CPM） is important for subsequent evidence retrieval， evaluation of evidence quality， formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects， namely， the drug of Chinese patent medicine （D）， the specific disease stage （S）， comparison （C）， and specific outcome （O）， DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research， policy or standard documents， and clinical data are suggested for collecting clinical questions， and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition， the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.

Objective:To elucidate the effect of bepridil, an Na +/Ca 2+ exchanger (NCX) inhibitor, on the proliferation, migration and apoptosis of melanoma cells, and to explore their potential underlying mechanisms. Methods:Six paraffin-embedded tissue specimens were collected from 3 patients histopathologically diagnosed with melanocytic nevi and 3 patients histopathologically diagnosed with melanoma in the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January to December 2023. NCX1 expression in tissues was determined by immunohistochemical staining, and Western blot analysis was performed to verify the expression of NCX1 in primary melanocytes and melanoma cell lines A375, A875, SKMEL-28, M14, MV3, and SK-MEL-5. Cell counting kit 8 (CCK8) assay was conducted to evaluate the effect of bepridil at different concentrations on the viability of melanoma cells, and the proliferation curve was drawn to calculate the half inhibitory concentration (IC50) of bepridil. Some melanoma cells were then treated with bepridil at IC50 (bepridil groups), and cells treated with dimethyl sulfoxide-containing media served as control groups. Intracellular Ca 2+ levels were assessed in A375 and SK-MEL-28 cells using the Fluo-4 calcium assay kit, the migration and apoptosis of A375, SK-MEL-28, and A2058 cells were estimated by Transwell assay and flow cytometry respectively. The effects of bepridil treatment on gene expression and pathways in A375 cells were evaluated by transcriptome sequencing, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The content of reactive oxygen species (ROS) in melanoma cells after the bepridil treatment was detected by flow cytometry, and the expression of endoplasmic reticulum stress- and mitochondrial apoptotic pathway-related molecules was determined by Western blot analysis. Comparisons between two groups were performed by t test. Results:Immunohistochemical assay showed that the expression of NCX1 was significantly higher in the melanoma tissues (0.320 ± 0.020) than in the melanocytic nevus tissues (0.235 ± 0.008, t = 4.04, P = 0.016) ; Western blot analysis showed that the NCX1 protein bands were darker in color in the melanoma cell lines than in the primary melanocytes. CCK8 assay showed a gradual decrease in melanoma cell viability with increasing concentrations of bepridil. In the A375 and SK-MEL-28 cells, the fluorescence intensity of calcium was higher in the bepridil groups after the treatment with bepridil at IC50 (25 μmol/L) (64.82 ± 2.98, 75.84 ± 2.07, respectively) than in the corresponding control groups (37.10 ± 2.33, 66.54 ± 1.47, respectively, both P < 0.05) ; in the A375, SK-MEL-28, and A2058 cells, the migration ability was lower in the bepridil groups (103.00 ± 9.07, 67.33 ± 7.22, 61.33 ± 1.76, respectively) than in the corresponding control groups (400.00 ± 25.17, 276.70 ± 14.63, 116.00 ± 10.69, respectively, all P < 0.05), while their apoptosis rates were higher in the bepridil groups (5.72% ± 0.06%, 13.58% ± 0.86%, 25.76% ± 1.95%, respectively) than in the corresponding control groups (3.99% ± 0.50%, 6.47% ± 0.88%, 8.01% ± 0.36%, respectively, all P < 0.05). Transcriptome sequencing revealed 119 up-regulated genes and 164 down-regulated genes in bepridil-treated A375 cells compared with control cells, and the differentially expressed genes were mainly associated with metabolic pathways, endoplasmic reticulum stress, and tumor-related pathways. The ROS levels were higher in bepridil-treated A375, SK-MEL-28, and A2058 cells (1 907 ± 33, 7 607 ± 535, 3 380 ± 300, respectively) than in the corresponding control groups (1 646 ± 16, 4 386 ± 163, 2 110 ± 66, respectively, all P < 0.05). Western blot analysis showed that the expression of C/EBP homologous protein and activating transcription factor 4 was higher in bepridil-treated A375 and SK-MEL-28 cells than in the corresponding control groups, but was lower in the A375 and SK-MEL-28 cells treated with bepridil and BAPTA (a calcium chelator) than in the corresponding cells treated with bepridil alone. Conclusion:The NCX inhibitor bepridil could increase intracellular Ca 2+ levels, suppress the proliferation and migration, and promote the apoptosis of melanoma cells, which may be closely related to biological processes such as endoplasmic reticulum stress.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

Objective: To make a postural transfer belt for patients with cervical spinal cord injury, to reduce and prevent the corresponding nursing problems with traditional methods of transfer Methods: 44 patients with cervical spinal cord injury admitted to the ward from January to June 2017 were selected as the control group by traditional methods of postural metastasis, and 48 patients with cervical spinal cord injury admitted to the ward from July to December 2017 were selected as the observation group by using self-made transfer belt. Results: Number of the skin injury caused by transfer in observation group was 0 cases, in control group was four cases, and there was significant difference (χ²=1.91, P=0.049). Falls occur due to metastasis: there were 0 cases in the observation group and five cases in the control group, there was significant difference (χ²=2.39, P=0.026). The number of caregivers in the observation group decreased on average (1.21±0.08), and the number of caregivers in the control group decreased on average (0.86±0.09). The differences between the two groups are statistically significant (t=2.905, P=0.005). The results of the investigation on the escorts in the observation group showed that 46 (95.8%) people believed that the transfer belt was convenient for patients. 47 people believed that the transfer belt was safer and more labor-saving to use, accounting for 97.9%, and 47 people believed that the transfer belt would continue to be used when they went home, who occupied 97.9%. Conclusion The self-made transfer belt is convenient for the caregivers to carry the patients with cervical spinal cord injury, which effectively prevents the occurrence of skin injury, falls and other nursing problems, and improves the quality and experience of the caregivers. This technology is worthwhile to spread.

Objective To explore the effects of piperine on cell proliferation and migration in angiotensin Ⅱ (Ang Ⅱ)-treated rat airway smooth muscle cells (ASMCs).Methods The primary ASMCs of rats were cultured by improved tissue-piece digestion inoculation and trypsin digestion.MTT assay was used to detect the effects of Ang Ⅱ and Ang Ⅱ receptor antagonist losartan on cell proliferation activity.After treatment with Ang Ⅱ and piperine, the cell proliferation activity, the cell cycle distribution and the cell migration were detected by MTT, flow cytometry and Transwell assay respectively.ERK1/2 inhibitor PD98059 and losartan were then applied to determine the expression of cyclin D1, MMP-9, p-ERK1/2, ERK1/2, and β-actin proteins by Western blot assay.Results After 24 h culture, Ang Ⅱ treatment promoted the cell proliferative activity in rat ASMCs (P<0.05), and the promotive effect of 10-7 mol/L Ang Ⅱ was the most significant.Additionally, losartan blocked the Ang Ⅱ-induced cell proliferative activity in rat ASMCs (P<0.05).10-7 mol/L Ang Ⅱ treatment resulted in the elevated cell proliferative activity, higher S phase fraction, increased migrated cell number, and enhanced expression of cyclin D1, MMP-9and p-ERK1/2 proteins (P<0.05);these effects were dose-dependently reversed by piperine.Both PD98059 and losartan blocked Ang Ⅱ-induced expression of p-ERK1/2, cyclin D1 and MMP-9 proteins in rat ASMCs.Conclusions Piperine may inhibit Ang Ⅱ-induced cell proliferation and cell migration via ERK1/2 signaling pathway in rat ASMCs.