This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

AIM: To observe the effect of Esketamine combined with sufentanil on analgesia and emotion after thoracoscopic radical resection of lung cancer. METHODS: A total of 108 patients undergoing thoracoscopic radical resection of lung cancer were randomly divided into three groups: Esketamine plus sufentanil patient-controlled analgesia group (S group), low-dose sufentanil patient-controlled analgesia group (LC group) and high-dose sufentanil patient-controlled analgesia group (HC group). PCIA was performed after operation. The formula of analgesia pump in group S: Esketamine 1.2 mg/kg, sufentanil 1 μg/kg, LC group analgesic pump formula: sufentanil 1 μg/kg; Formula of analgesic pump in HC group: sufentanil 1.5 μg/kg; Tropisetron 10 mg was added to three groups of analgesia pumps, and normal saline was diluted to 100 mL. Observe the visual analogue scale (VAS) and Ramsay sedation score of resting and exercise pain at 6 h (T

OBJECTIVE: To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). METHODS: A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. RESULTS: The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). CONCLUSIONS The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.
Humans ; Polymorphism, Single Nucleotide ; Prospective Studies ; Vitamin D-Binding Protein/genetics* ; Acute Disease ; Pancreatitis/genetics* ; Genotype ; Prognosis

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.
Humans ; Medicine, Chinese Traditional ; Psoriasis/drug therapy*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*