HBV DNA integration （iDNA） is the core barrier that must be overcome to achieve functional cure for chronic hepatitis B （CHB） and to prevent the occurrence of hepatocellular carcinoma （HCC）. During reverse transcription， 5%　—　10% of viral genomes are converted into double-stranded linear DNA that is randomly inserted into host chromosomes， generating stable iDNA and continuously producing HBsAg， thereby driving B- and T-cell immune exhaustion and locking the host in an immune-tolerant state. The process of iDNA runs throughout the entire natural history of HBV infection， and the viral enhancers it carries can promote clonal hyperplasia of indeterminate potential， accumulate pre-neoplastic mutations， and ultimately lead to HCC. Although long-term nucleos（t）ide analog or interferon therapy can suppress viral replication and reduce the formation of new integrations， existing therapies still fail to eliminate existing iDNA. Therefore， there is an urgent need for innovative strategies that can precisely target integration breakpoints， epigenetically silence iDNA， or eradicate integrated clones， so as to significantly increase the functional cure rate of CHB and fundamentally reduce the risk of HCC.

AIM: To explore the impacts of wearing orthokeratology lenses on the ocular surface and meibomian gland of children and adolescents in high-altitude areas.METHODS: Retrospective study. Myopic children and adolescents who visited at the ophthalmology department and received orthokeratology lens from June 2023 to December 2023 were selected as orthokeratology group, and those who visited and wore regular spectacle group during the same period were selected as regular spectacle group. Then the ocular surface disease index(OSDI)score, tear meniscus height, non-invasive breakup time(NIBUT)[first NIBUT(fNIBUT), average NIBUT(avNIBUT)], and meibomian gland score were compared between the two groups before wearing lenses, and at 1, 3, 6, and 12 mo after wearing lenses.RESULTS: A total of 80 children(160 eyes)with myopia were included in this study. Among them, 40 cases(80 eyes)were in the orthokeratology lens group, with 25 males and 15 females and an average age of 11.33±2.76 years old, and 40 cases(80 eyes)were in the regular spectacle group, with 23 males and 17 females and an average age of 11.58±2.94 years old. The OSDI scores and tear meniscus heights showed no clear difference between two groups at various time points before and after wearing glasses(all P>0.05). The fNIBUT and avNIBUT of the orthokeratology lens group decreased compared with the regular spectacle group at 6 and 12 mo after wearing lenses, and meibomian gland score of the orthokeratology group was higher than that of the regular spectacle group at 12 mo after wearing lenses(all P<0.001). Among them, the fNIBUT and avNIBUT of the orthokeratology lenses group at 3, 6, and 12 mo after wearing glasses were lower than those before wearing glasses(all P<0.05). Moreover, the meibomian gland scores of the orthokeratology lenses group at 12 mo after wearing glasses were higher than those before wearing glasses, and 1, 3, and 6 mo after wearing glasses(all P<0.05), while there was no statistical difference in fNIBUT, avNIBUT, and meibomian gland score at each time point in the regular spectacle group(all P>0.05).CONCLUSION: Long term wearing of orthokeratology lenses can shorten the NIBUT of myopic children and adolescents in high-altitude areas, and have a certain impact on their meibomian gland function.

ObjectiveTo observe the expression of miR-139/Notch1 axis and macrophage polarization in the homing changes of bone mesenchymal stem cells （BMSCs） in asthmatic rats， and to explore the possible mechanism of immune regulation by BMSCs during asthma. Methods30 male SD rats were randomly divided into three groups： normal control group， model control group and BMSCs implantation group， with 10 rats in each group. BMSCs labeled with CFSE were infused into the body of asthmatic rats through the tail vein， and the homing status of BMSCs in asthmatic lung tissue was detected by flow cytometry. Changes in the proportion of inflammatory cells in alveolar lavage fluid were detected by Wright-Giemsa Stain； the levels of macrophage polarization cytokines IFN⁃γ，IL-13，CD80 and CD206 in rat serum were detected by ELISA； the miR-139， Notch1， NOS2， Arg1 and CXCR4 in lung tissue were detected by RT-qPCR. ResultsCompared with the NC group， the expression of serum CD80 and IFN⁃γ in the MC group decreased， while the expression of IL-13 and CD206 increased （P<0.01）. The expression of miR⁃139 in lung tissue of MC group rats decreased， and the expression of macrophage polarization markers NOS2， Arg1， and homing marker CXCR4 genes increased （P<0.01）. Compared with the MC group， the expression of IFN-γ of rats in BMSCs group increased， while the expression of IL-13 and CD206 decreased （P<0.01）. The expression of miR⁃139， CXCR4， and SDF⁃1 mRNA in the lung tissue of rats of BMSCs group increased， while the expression of Notch1， NOS2， and Arg1 decreased （P<0.01）. Correlation analysis showed that CXCR4 was positively correlated with miR⁃139 （P<0.05）， while CXCR4 was negatively correlated with Notch1 （P<0.05）. SDF⁃1 and IFN⁃γ was a positively correlated （P<0.05）， while SDF⁃1 was negatively correlated with Arg1 and CD206 （P<0.05）. ConclusionThe miR⁃139/Notch1 axis can promote BMCs homing in asthmatic rats by affecting macrophage polarization in asthma.

This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name， origin， harvesting and processing， quality and others by consulting ancient and modern literature， in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application， and it derives its name from its distinctive growth pattern， featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus， leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research， it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu， and throughout history， Baidu has been recognized as its official name， though it also bears alternative names such as Baibing， Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia， S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia）. Additionally， Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China， exhibiting a wide distribution. Historically， wild harvesting was predominant， but cultivation is now established. In ancient times， the harvesting time was mostly in the second， third， and eighth lunar months， when roots were harvested and dried. Nowadays， it is more common to pick and excavate in the spring and autumn seasons. After excavation， the roots are washed， fibrous roots removed， briefly blanched in boiling water or steamed until no white core remains， and then sun-dried or oven-dried. In ancient times， the processing of Stemonae Radix primarily involved roasting（stir-frying）， wine roasting， or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials， ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick， robust stems with firm texture". Evaluating quality with authenticity， since the Song dynasty， it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin， reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history， including relieving coughs， eliminating phlegm and parasites. Based on the research results， it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix， the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas， and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.

This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name， origin， harvesting and processing， quality and others by consulting ancient and modern literature， in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application， and it derives its name from its distinctive growth pattern， featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus， leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research， it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu， and throughout history， Baidu has been recognized as its official name， though it also bears alternative names such as Baibing， Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia， S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia）. Additionally， Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China， exhibiting a wide distribution. Historically， wild harvesting was predominant， but cultivation is now established. In ancient times， the harvesting time was mostly in the second， third， and eighth lunar months， when roots were harvested and dried. Nowadays， it is more common to pick and excavate in the spring and autumn seasons. After excavation， the roots are washed， fibrous roots removed， briefly blanched in boiling water or steamed until no white core remains， and then sun-dried or oven-dried. In ancient times， the processing of Stemonae Radix primarily involved roasting（stir-frying）， wine roasting， or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials， ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick， robust stems with firm texture". Evaluating quality with authenticity， since the Song dynasty， it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin， reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history， including relieving coughs， eliminating phlegm and parasites. Based on the research results， it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix， the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas， and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.

Objective: To investigate the dyadic coping level and and its influencing factors among patients with chronic obstructive pulmonary disease (COPD), so as to provide the basis for reinforcing their self-management. Methods: Patients with COPD visiting the Hangzhou First People's Hospital from January to December 2024 were selected using a convenience sampling method. The demographic information was collected by questionnaire survey. The dyadic coping level, self-efficacy, and intimate relationship satisfaction were evaluated using the Dyadic Coping Inventory, Self-Efficacy for Managing Chronic Disease Scale, and Quality of Relationship Index, respectively. Factors affecting dyadic coping level among patients with COPD were analyzed using multiple linear regression model. Results: A total of 129 (54.66%) male patients and 107 (45.34%) female patients were investigated. Among them, 175 (74.15%) patients aged 60 to 84 years. The mean dyadic coping score was (124.10±8.95) points, self-efficacy score was (39.22±5.18) points, and intimate relationship satisfaction score was (5.16±1.08) points among patients with COPD. Multiple linear regression analysis identified that dyadic coping level was higher among patients with COPD who aged 41-<60 years (β'=0.182), had high school/secondary specialized educational level (β'=0.201) or college degree or above educational level (β'=0.325), had monthly household income per capita of 3 000-6 000 yuan (β'=0.196) or >6 000 yuan (β'=0.308), had disease duration ≥5 years (β'=0.214), scored high in self-efficacy (β'=0.209) and intimate satisfaction (β'=0.231). Conclusion The dyadic coping level among patients with COPD was related to age, educational level, monthly household income per capita, disease duration, self-efficacy and intimacy satisfaction.

OBJECTIVE To evaluate the long-term cost-effectiveness of insulin degludec and insulin aspart （IDegAsp） in patients with type 2 diabetes mellitus （T2DM） in China. METHODS A cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system， using the CORE diabetes model to simulate long-term （20-year） health and economic outcomes. Baseline cohort characteristics and treatment effect data were derived from the CREATE study. The prices of glucose- lowering drugs were obtained from medical insurance payment standards and the average winning bid prices in the follow-up round of the specialized centralized procurement for insulin， while the daily dosages were derived from the CREATE study. The costs of complications and utility values were obtained from published literature， with a discount rate of 5%. One-way sensitivity analysis， scenario analysis， and probabilistic sensitivity analysis were performed to verify the robustness of the results. RESULTS Patients switching from previous once-daily basal insulin regimens to IDegAsp therapy gained an incremental 0.190 quality-adjusted life year （QALY） with direct medical cost savings of 42 163.58 yuan. For those switching from premixed insulin therapies， IDegAsp treatment provided 0.130 incremental QALY and reduced direct healthcare costs by 41 129.11 yuan. The outcome was significantly influenced by the discount rate and the cost of complications. Probabilistic sensitivity analysis and scenario analysis confirmed the robustness of these findings. CONCLUSIONS Switching from previous daily basal insulin or premixed insulin regimens to IDegAsp in Chinese patients with T2DM can improve patients’ long-term health outcomes and achieve cost savings， making it a more cost-effective treatment option.

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals