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.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P＜0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P＜0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P＜0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P＜0.05 or P＜0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P＜0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P＜0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.

Objective:To study the therapeutic effect of cardiac rehabilitation in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI)and its effect on inflammatory factors.Methods:A total of 94 AMI patients after PCI admitted in Hospital of China University of Geosciences(Wuhan)between June 2020 and August 2021 were selected and randomly divided into control group(n=47,routine therapy)and study group(n=47,individualized cardiac rehabilitation therapy based on routine therapy).Cardiopulmonary exercise indexes,blood lipid indexes,inflamma-tory factors and cardiac function indexes were compared between two groups before and 3 months after treatment.Results:Compared with control group after treatment,participants in study group had significant higher anaerobic threshold[(15.46±3.07)ml·min-1·kg-1 vs.(19.37±3.27)ml·min 1·kg-1],maximal oxygen uptake[(21.26±4.05)ml·min-1·kg-1 vs.(25.31±4.10)ml·min-1·kg-1],left ventricular ejection fraction(LVEF)[(52.20±5.75)％vs.(57.91±5.17)％],6min walking distance(6MWD)[(430.58±43.87)m vs.(481.52±44.57)m]and levels of high density lipoprotein cholesterol(HDL-C)[(1.30±0.32)mmol/L vs.(1.49±0.35)mmol/L]and interleukin(IL)-10[(5.45±0.55)pg/ml vs.(6.19±0.59)pg/ml](P＜0.01 all),and significant lower levels of triglyceride(TG)[(1.88±0.65)mmol/L vs.(1.54±0.63)mmol/L],total cholesterol(TC)[(3.49±0.54)mmol/L vs.(3.13±0.47)mmol/L],low density lipoprotein cholesterol(LDL-C)[(2.12±0.59)mmol/L vs.(1.57±0.52)mmol/L],tumor necrosis factor-α(TNF-α)[(128.34±14.5)pg/ml vs.(99.28±8.51)pg/ml],leptin(LEP)[(623.49±61.27)pg/ml vs.(483.57±47.61)pg/ml]and N terminal pro B-type natriuretic peptide(NT-proBNP)[(396.59±18.12)pg/ml vs.(302.96±17.56)pg/ml](P＜0.05 or＜0.01).Conclusion:Cardiac rehabilitation therapy can significantly im-prove the blood lipid levels,cardiac function and exercise endurance,and effectively reduce the levels of inflammatory fac-tors in AMI patients after PCI,which is an important component of secondary prevention in these patients.

This paper introduces Professor Huang Huang's clinical experience in treating depression with modified classical pre-scriptions of Zhongjing.Professor Huang Huang inherited and summarized Zhongjing's academic thoughts on treating emotional disea-ses,and formulated Jieyu Chufan Recipe by combining Banxia Houpu Decoction with Zhizi Houpu Decoction.He believes that depres-sion is characterized by qi stagnation and phlegm obstruction,as well as internal disturbance of stagnation fire,and formulated a treat-ment method of clearing heat and eliminating restlessness,relieving depression and resolving phlegm.Professor Huang Huang uses Jieyu Chufan Recipe as the basic prescription,and combines relevant classical prescriptions with modifications to treat depression ac-cording to different constitutions and syndromes of patients,achieving satisfactory clinical results.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins