Diabetic retinopathy（DR）， as one of the most common and serious microvascular complications of diabetes mellitus， seriously threatens human health， and belongs to "Xiaoke eye diseases" in traditional Chinese medicine（TCM）， which has been richly experienced by medical practitioners through the ages， but is mostly recorded in a piecemeal manner and has not been systematically researched. This disease is featured by long course and repeated attack， and is refractory， which belongs to the research category of "persistent illness entering collaterals". Systematic establishment of TCM collateral disease theory for guiding prevention and treatment of DR has important clinical value. On the basis of close correlation between tertiary collaterals at the terminal of collaterals and capillaries and microcirculation， the concept of "tertiary collaterals-microvascular" is proposed. It is pointed out that DR falls within the scope of "tertiary collaterals-microvascular" diseases， and presents four types of micro-pathological characteristics， including stasis， insufficiency， growth and bleeding of tertiary collaterals. It is concluded that "deficiency of both Qi and Yin" is the basic pathogenesis of DR， and "blood stasis and collateral obstruction" is the important pathogenesis and key factor. Thus， the treatment method of "dispersing blood stasis， dredging collateral， tonifying Qi and Yin， stopping hemorrhage and improving eyesight" is determined， and the formula of Tongluo Mingmu capsules is developed. The article tightly focuses on the pathological changes such as stasis， growth， insufficiency and bleeding of collaterals， addresses both symptoms and root causes， and plays a synergistic role of both dispersing stasis and stopping bleeding. In this way， it can realize the purpose of tonifying Qi and Yin to replenish the essence， dispersing stasis and dredging collaterals to meet the requirement， as well as stopping hemorrhage and improving eyesight to deal with changes. Fundamental researches demonstrate that Tongluo Mingmu capsules has synergy effects of protecting both retinal capillaries and retinal cells. Phase-Ⅲ clinical trial of new drug has proven definite clinical efficacy and good safety， which provides a new drug choice for enhancing clinical effect of DR， and further supports the scientific value of Luobing theory in preventing and treating DR and other clinically significant diseases.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

ObjectiveTo investigate the effect and mechanism of ginsenoside Rg₁ （G-Rg₁） combined with hirudin in treating myocardial fibrosis in the mouse model of acute myocardial infarction （AMI）. MethodSeventy-five C57BL/6N mice were randomized into sham， model， G-Rg₁ （20 mg·kg^-1）， hirudin （20 mg·kg^-1）， and G-Rg₁ （20 mg·kg^-1） + hirudin （20 mg·kg^-1） groups. The mouse model of AMI was established by ligation of the anterior descending branch of the left coronary artery and continued gavage for 4 weeks. The success of the modeling was judged by ECG changes of mice before and after ligation. The heart weight index， echocardiography， myocardial fibrosis， type Ⅰ collagen α1（COL1A1）， platelet-endothelial cell adhesion molecule-1 （PECAM-1/CD31）， α-smooth muscle actin （α-SMA）， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） were measured before and after treatment. ResultAfter ligation of the anterior descending branch of the left coronary artery， the R wave and T wave merged into a tall tented wave， and the ST segment presented a "damaged" change， indicating that the model was successfully prepared. Compared with the sham group， the model group showed dull and dry hair， slow movement， increased heart weight index （P<0.01）， decreased left ventricular ejection fraction （EF） and left ventricular shortening fraction （FS） （P<0.01）， increased left ventricular end-diastolic diameter （LVEDd） and left ventricular end-systolic diameter （LVESd） （P<0.01）， disarranged myocardial fibers， collagen fiber hyperplasia （P<0.01）， increased expression of COL1A1 （P<0.01）， upregulated protein levels of ICAM-1 and VCAM-1 （P<0.01）， downregulated CD31 expression， and upregulated α-SMA expression （P<0.01）. Compared with the model group， the treatment groups recovered the above indexes in different degrees （P<0.05， P<0.01）， and the combined group had better effect （P<0.05）. ConclusionG-Rg₁ combined with hirudin can ameliorate myocardial fibrosis after AMI by inhibiting the expression of adhesion molecular protein in the heart tissue， reducing the adhesion of inflammatory cells， alleviating cardiac inflammation， and inhibiting cardiac endothelial-to-mesenchymal transition.

OBJECTIVE To explore the effects and potential mechanism of asperuloside （ASP） on colonic pathological injury and inflammatory response in rats with ulcerative colitis （UC） based on the stimulator of interferon genes （STING）/TANK binding kinase 1 （TBK1）/interferon regulatory factor 3 （IRF3） signaling pathway. METHODS A UC rat model was established by intrarectal injection of trinitrobenzenesulfonic acid and ethanol. The successfully modeled rats were allocated to model group， low- dose ASP group （17.5 mg/kg）， high-dose ASP group （35 mg/kg）， and high-dose ASP+STING activator ADU-S100 group （35 mg/kg ASP+20 mg/kg ADU-S100）， with 16 rats in each group. Another 16 healthy rats were selected as control group， by intrarectally injecting with normal saline. The rats in each group were given the corresponding drug solutions or normal saline by gavage or/and intraperitoneal injection once a day for 14 consecutive days. Twenty-four hours after the last administration， the disease activity index （DAI） and colonic mucosal damage index （CMDI） were employed to assess the severity of UC and colonic mucosal damage in each group. Colonic tissue pathological changes were observed， and histopathological scores were recorded. Apoptosis in colonic tissue， levels of inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interferon-β （IFN-β）， interleukin-4 （IL-4）， IL-10]， and expressions of pathway-related proteins [STING， TBK1， IRF3， nuclear factor-κB p65 （NF-κB p65）] were detected. RESULTS Compared with the control group， the model group showed severe destruction of colonic mucosa and glandular structure， mucosal epithelial erosion， crypt loss， marked inflammatory cell infiltration； it also demonstrated significant increase in DAI score， CMDI score， colonic histopathological score， apoptosis rate， the levels of TNF-α and IFN-β， and protein expression of STING and phosphorylation levels of TBK1， IRF3 and NF-κB p65， while the levels of IL-4 and IL-10 were significantly decreased （P＜0.05）. Compared with the model group， the low- and high-dose ASP groups showed relatively intact colonic mucosal structure， orderly glandular arrangement， reduced congestion and edema， and markedly reduced inflammatory cell infiltration and ulcers； all quantitative indicators were significantly improved， with the high-dose group showing more pronounced improvements than the low-dose group （P＜0.05）. Compared with the high-dose ASP group， the above indicators of rats in the high-dose ASP+STING activator group were significantly reversed （P＜0.05）. CONCLUSIONS ASP may alleviate colonic pathological injury and inflammatory response in UC rats by inhibiting the STING/TBK1/IRF3 signaling pathway.

Objective: To systematically evaluate the incidence and influencing factors of depression in family caregivers of Alzheimer's disease (AD) patients, so as to provide the basis for the prevention and treatment of depression among the family caregivers of AD patients. Methods: Publications pertaining to depression in family caregivers of AD patients were retrieved from CNKI, Wanfang Data, PubMed and other databases from the time of their establishment to June 15, 2023. The evaluation criteria recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale were used to assess the quality of cross-sectional and cohort studies, respectively. Stata 16.0 and Revman 5.4 softwares were used to conduct a meta-analysis on the incidence and influencing factors of depression in family caregivers of AD patients. Sensitivity analysis and publication bias assessment were also performed on the results. Results: A total of 2 324 articles were retrieved, and ultimately 14 articles were included, with a total sample size of 8 313 individuals. There were 6 high-quality articles and 8 moderate-quality articles. Meta-analysis showed that the incidence of depression in family caregivers of AD patients was 37.5% (95%CI: 30.2%-45.1%). Factors associated with depression included patients' high degree of dementia (OR=1.718, 95%CI: 1.059-2.789), patients' low scores on Activities of Daily Living Scale (OR=1.344, 95%CI: 1.059-1.706), patients' psychobehavioral abnormalities (OR=1.248, 95%CI: 1.155-1.348), long duration of caregiving (OR=1.998, 95%CI: 1.637-2.437), less involvement of other family members in caregiving (OR=1.597, 95%CI: 1.237-2.061), low educational level (OR=1.191, 95%CI: 1.044-1.359), poor caregiving skills (OR=3.060, 95%CI: 2.257-4.149), poor self-rated health (OR=2.536, 95%CI: 1.114-5.771) and social support (OR=0.424, 95%CI: 0.232-0.774). The results of depression incidence demonstrated good stability with no significant publication bias. However, publication bias was observed in the influencing factors for depression, which were patients' high degree of dementia and patients' low scores on Activities of Daily Living Scale. Conclusions The incidence of depression in family caregivers of AD patients ranges from 30.2% to 45.1%. It is primarily influenced by the severity of patients' symptoms and ability to perform daily activities, and caregivers' educational level, caregiving skills, health status, caregiving duration and social support.

Objective To investigate the effect of tetrandrine(Tet)on injury of primary human articular chondro-cytes induced by interleukin-1β(IL-1β).Methods Human articular chondrocytes were divided into control group,IL-1β group,hypoxia inducible factor(HIF-1α)inhibitor group[2-methoxyestradiol(2-ME2)group],Tet groups containing low,medium and high concentrations.Each group has six replicated samples.MTT assay was used to de-tect the viability of cells;cell apoptosis was detected by flow cytometry;the level of inflammatory related factors like tumor necrosis factor-α(TNF-α),matrix metalloproteinase 3(MMP-3),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and the activity of antioxidant factors like super oxide dismutase(SOD)and glutathione peroxides(GPx)in cells were detected by ELISA;Western blot was used to detect the expression of HIF-1α and VEGF in cells.Results Compared with the control group,the apoptosis rate,level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in IL-1β group all increased,the cell survival rate and the activity of SOD and GPx significantly decreased(P＜0.05);compared with IL-1β group,the apoptosis rate,the level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in 2-ME2 group and Tet groups with low,medium,and high concentration significanthy decreased(P＜0.05).The cell survival rate and the activity of SOD and GPx significantly increased(P＜0.05).Conclusions Tetrandrine attenuates IL-1β-in-duced injury of human articular chondrocytes.

Objective:To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing.Methods:In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6 th, 2023 (6 th week) to May 28 th (21 th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results:There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10 th week, with H1N1 as the predominant one from the 6 th to 9 th week (10.0%-50.0%) and then H3N2 from the 10 th to 16 th week (15.0%-90.0%). HMPV was detected from the 15 th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20 th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15 th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7 th week 10% (6/60), to peak in the 11 th week 31.8% (21/66). H3N2 was detected from the 8 th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12 th week 1.3% (1/80), reaching 30.4% (35/115) at 19 th week. The positive rate of HMPV reached 12.1% (14/116) at 21 th week. Conclusions:In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

Primary cutaneous T-cell lymphoma (CTCL) is the most common malignant proliferative disease of mature memory T cells, and the most common subtype is mycosis fungoides/Sézary syndrome. The local treatment in the skin is mainly given in patients with early CTCL and good prognosis can be achieved generally, while for patients in advanced stage, there is no standard recommended treatment regimen due to the poor efficacy of traditional therapy. In recent years, with the development of immune-targeted drugs for T-cell lymphoma, a variety of new drugs have shown good efficacy in the clinical treatment of CTCL, including histone deacetylase inhibitors, monoclonal antibodies, chimeric antigen receptors T-cell therapy. This paper reviews the research progress of immune-targeted therapy drugs for advanced mycosis fungoides/Sézary syndrome.