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.

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.

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 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 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 study aims to explore the molecular regulation mechanism of the differential accumulation of flavonoids in the leaves and roots of Sarcandra glabra. Liquid chromatography-mass spectrometry(LC-MS) and high-throughput transcriptome sequencing(RNA-seq) were employed to screen out the flavonoid-related differential metabolites and differentially expressed genes(DEGs) encoding key metabolic enzymes. Eight DEGs were randomly selected for qRT-PCR verification. The results showed that a total of 37 flavonoid-related differential metabolites between the leaves and roots of S. glabra were obtained, including pinocembrin, phlorizin, na-ringenin, kaempferol, leucocyanidin, and 5-O-caffeoylshikimic acid. The transcriptome analysis predicted 36 DEGs associated with flavonoids in the leaves and roots of S. glabra, including 2 genes in the PAL pathway, 3 genes in the 4CL pathway, 2 genes in the CHS pathway, 4 genes in the CHI pathway, 2 genes in the FLS pathway, 1 gene in the DFR pathway, 1 gene in the CYP73A pathway, 1 gene in the CYP75B1 pathway, 3 genes in the PGT1 pathway, 6 genes in the HCT pathway, 2 genes in the C3'H pathway, 1 gene in the CCOAOMT pathway, 1 gene in the ANR pathway, 1 gene in the LAR pathway, 2 genes in the 3AT pathway, 1 gene in the BZ1 pathway, 2 genes in the IFTM7 pathway, and 1 gene in the CYP81E9 pathway. Six transcription factors, including C2H2, bHLH, and bZIP, were involved in regulating the differential accumulation of flavonoids in the leaves and roots of S. glabra. The qRT-PCR results showed that the up-or down-regulated expression of the 8 randomly selected enzyme genes involved in flavonoid synthesis in the leaves and roots of S. glabra was consistent with the transcriptome sequencing results. This study preliminarily analyzed the transcriptional regulation mechanism of differential accumulation of flavonoids in the leaves and roots of S. glabra, laying a foundation for further elucidating the regulatory effects of key enzyme genes and corresponding transcription factors on the accumulation of flavonoids in S. glabra.
Metabolome ; Gene Expression Regulation, Plant ; Flavonoids ; Gene Expression Profiling ; Transcriptome ; Transcription Factors/metabolism*

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

Along with intensification of social and life pressures as well as the interference from various psychological stresses， the number of people suffering from insomnia is constantly increasing， and resistance and addiction of western medicine treatment have received much attention. Safe， effective and characteristic therapeutic drug are urgently needed in clinical practices. Chinese eight-word principle of health preservation via dredging collaterals integrates health-preservation quintessence of traditional major schools of Confucianism， Taoism， Buddhism and medicine， and becomes a new theory guiding health preservation in traditional Chinese medicine. The pathogenic characteristics of "deficiency of kidney-essence， insufficiency of heart blood and loss of spirit and consciousness" as well as the therapeutic methods of "tonifying the kidney， invigorating the brain， nourishing the heart and tranquilizing" were proposed on the basis of "conserving strength" and "calming" theory included in Chinese eight-word principle of health preservation via dredging collaterals and in combination with the opinions of "primordial spirit in brain" and "consciousness spirit in heart" described by recent medical doctor ZHANG Xichun in Intergrating Chinese and Western Medicine. The development of innovative Chinese medicine Yishen Yangxin Anshen tablets reflects theoretical innovation， original formula， outstanding pharmacological characteristics and definite clinical effect， and proves scientific value of Chinese eight-word principle of health preservation via dredging collaterals.

As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroG^fbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.
Escherichia coli/metabolism* ; Tryptophan ; Metabolic Engineering ; Bioreactors ; Metabolic Networks and Pathways