ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

This paper summarized Professor ZHOU Zhaoshan's clinical experience in treating bronchial asthma （abbreviated as asthma） by stages with dampness-draining method. It is believed that pathogenic dampness is the key pathological factor in the onset of asthma. Dampness accumulates into water， which gathers into rheum； the condensed rheum forms phlegm， which lingers in the lungs. When external pathogens trigger the latent phlegm， phlegm and qi become mutually obstructed， leading to airway obstruction， disrupted qi movement， and upward reversal of lung qi， thereby resulting in asthma attacks. The treatment emphasizes a stage-based approach. During acute attacks， the main syndromes include cold-damp obstructing the lungs， damp-heat accumulating in the lungs， and shaoyang （少阳） constraint with heat. For the syndrome of cold-damp obstructing the lungs， a self-formulated Wenfei Shenshi Decoction （温肺渗湿汤） is used to warm the lungs and disperse cold， drain dampness and relieve panting； for the syndrome of damp-heat accumulating in the lungs， a self-formulated Qingfei Shenshi Decoction （清肺渗湿汤） is employed to clear the lungs and expel heat， drain dampness and relieve asthma； and for the syndrome of shaoyang constraint with heat， a self-formulated Chaihu Shenshi Decoction （柴胡渗湿汤） is administered to harmonize the shaoyang， clear heat and drain dampness. During the remission stage， treatment is based on the underlying kidney-deficiency constitution， and a self-formulated Bushen Shenshi Decoction （补肾渗湿汤） is formulated to tonify the kidneys and drain dampness， improve qi reception and relieve panting.

Objective:To investigate the difference in brain activity intensity between methamphetamine (MA) dependent patients (MA group) and healthy controls (control group) using fractional amplitude of low-frequency fluctuation (fALFF), and to establish a classification model between these two groups using support vector machine (SVM).Methods:From February 2014 to October 2019, a total of 46 male MA-dependent patients and 46 male healthy controls were recruited from the Affiliated Kangning Hospital of Ningbo University. The study collected resting-state functional magnetic resonance imaging (rs-fMRI) data and analyzed the differences in brain functional activity between the two groups. This analysis was conducted using both static and dynamic fractional amplitude of low-frequency fluctuations (d-fALFF). Additionally, the study examined the correlation between fALFF/d-fALFF values in specific brain regions and the total scores, as well as each factor score, of the Brief Psychiatric Rating Scale (BPRS). Furthermore, the relationship between fALFF/d-fALFF values and the age of first use and total dose of MA in the MA group was investigated. Finally, the fALFF map and d-fALFF map of brain regions with significant differences between groups were used as features for constructing classification.Results:Compared to the healthy control group, those dependent on MA showed significantly increased fALFF mainly in the nucleus accumbens, caudate nucleus, thalamus, and amygdala nucleus( t=-5.21--2.72, all P<0.05). The MA group exhibited decreased fALFF in the superior frontal gyrus, middle frontal gyrus, orbital gyrus, and cingulate gyrus( t=3.59-5.00, all P<0.05). Most of the brain regions with decreased d-fALFF overlapped with those exhibiting decreased fALFF( t=3.33-4.87, all P<0.05). The results of the correlation analysis showed that the fALFF value of the right nucleus accumbens was positively correlated with the age of first use of MA ( r=0.537, P<0.001). There is no significant relationship between the abnormal fALFF and d-fALFF values in the MA group and the total scores and each factor scores of BPRS, as well as the total dose of MA taken (after removing outliers). Based on fALFF and d-fALFF values, the SVM classifier achieved accuracies of 90.33%±6.89% and 71.56%±7.80%, respectively. Conclusions:There are significant abnormalities in the low-frequency fluctuation of the resting brain in patients dependent on MA. These abnormalities reflect the rigidity of prefrontal cortex activity, functional impairment, and dysfunction of the anti-reward system. These factors may be one of the causes for MA dependent behavior and repeated episodes. In addition, the fALFF values may be helpful for distinguishing MA dependent individuals from the control group.

Recurrence of malignant tumors after surgery and radiotherapy and chemotherapy is the main cause of death in patients.There is a basis for the prevention and treatment of malignant tumor recurrence with traditional Chinese medicine,but its clin-ical diagnosis and treatment still lacks the guidance of the core pathogenesis theory.This paper reviews the pathogenesis of malignant tumor recurrence from ancient times to the present.Based on the theory of cancer toxin pathogenesis and combined with the progress of modern medical research,the paper summarizes the core pathogenesis of malignant tumor recurrence,including"deficiency of healthy qi,recurrence of residual toxin"and"accumulation of phlegm and stasis,recurrence of cancer toxin".It proposes the prevention and treatment strategies of strengthening the healthy qi and consolidating the foundation,focusing on the coordination of the spleen and kid-ney,restraining the evil and toxin;resolving phlegm and removing stasis,focusing on promoting the expulsion of evil and clearing the remaining evil;protecting against cancer and detoxification,focusing on distinguishing the location and nature of disease,and classif-ying the use of herbals.

Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

This study aims to compare the vaccination rates and incidence of adverse reaction rates following administration of two domestically produced human papillomavirus (HPV) vaccines in individuals aged 9-30 years,investigate the impact of distinct manufacturing processes and vaccination schedules on adverse reaction rates. From November 2023 to June 2024, the Immunization Planning Department of Liuzhou Center for Disease Control and Prevention conducted a single-center, randomized, open-label, parallel-group trial using community-based recruitment of eligible participants aged 9 to 30 years. Participants were randomly assigned to receive either of two domestically produced HPV vaccines (Walrinvax or Cecolin). As specified in the vaccine package inserts, subjects were stratified into a two-dose regimen group (aged 9-14 years) and a three-dose regimen group (aged 15-30 years). Vaccination rates were recorded, and adverse reactions within 0-30 days post-vaccination were monitored. The results showed that a total of 400 participants were enrolled. Both the full vaccination rate and the timely completion rate were significantly higher in the two-dose regimen group compared to the three-dose regimen group (Fisher′s exact test, P<0.01; χ2=7.06, P<0.01). A total of 985 doses were administered. The overall adverse reaction rate was 18.78% (185/985), with local and systemic reactions occurring at 8.02% (79/985) and 10.76% (106/985), respectively. The most frequent adverse reactions were injection site pain (4.97%, 49/985) and fever (4.47%, 44/985). No grade 4 or special-interest adverse events were reported.The incidence of adverse reactions for the two domestic HPV vaccines with different production processes (at 0/6 months) was 13.96% (55/394) and 17.46% (69/395) respectively, with no statistically significant difference (χ2=1.83, P>0.05).The adverse reaction rate was significantly lower in the 9-14 years group (9.77%) compared the 15-30 years group (24.91%)(χ 2=35.67, P<0.01). In conclusion, both domestic HPV vaccines demonstrated a favorable safety profile in the 9-30 years age group, with mostly mild adverse reactions. Compared to the three-dose schedule (15-30 years group), the two-dose HPV vaccination schedule (9-14 years group) significantly reduced the incidence of adverse reactions and improved vaccination compliance.

Objective:To study the feasibility of design and harvest of free medial sural artery perforator flap with the "two-point and two-line method".Methods:From September 2022 to June 2023, Suzhou Ruihua Orthopaedic Hospital implemented the "two-point and two-line method" to guide preoperative perforator positioning and flap design. Thirty medial sural artery perforator flaps were successfully harvested with the method, and 21 wounds of hand and 9 of foot and ankle were reconstructed with the flaps. The size of soft tissue defects were 2.5 cm×2.5 cm-7.0 cm×14.5 cm, and the flaps size were 3.0 cm×3.0 cm-7.5 cm×15.0 cm. All donor sites were directly closed or by skin grafting. All patients were entered in 6-15 months of postoperative outpatient follow-up, and the recovery of donor and recipient sites was assessed by the comprehensive evaluation scales. The sensory function of the flaps was evaluated using the sensory function evaluation standard of British Medical Research Council (BMRC).Results:All perforators were successfully located with 47 perforators in total, and all of them were musculocutaneous perforator. It was found that there was 1 perforator in 14 flaps, 2 perforators in 15 flaps and 3 perforators in 1 flap. All 30 flaps survived after surgery, beside 2 flaps that had arterial insufficiency but survived successfully after surgical exploration. All donor sites healed in one stage. Comprehensive evaluation scale of flap was employed to evaluate the flaps and the scores were 84 points to 96 points with an average score of 92.5 points. The excellent and good grades were achieved in 27 flaps and 3 flaps, respectively, with a combined excellent and good rate at 100%. Sensation of the flaps was evaluated by BMRC with 1 flap of S 1, 17 of S 2 and 12 of S 3. Conclusion:The "two-point and two-line method" has been used in design of the perforator flap of medial sural artery. This method is simple and accurate, and is feasible and ideal in design of flaps before surgery.