19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Objective To investigate the surgical method and clinical outcome using the free anterolateral thigh flap with the medial gastrocnemius artery as the recipient artery for the repair of complex wounds in the lower leg. Methods A retrospective analysis was conducted on the clinical data of 11 patients with complex wounds in the lower leg admitted to Suzhou Ruihua Orthopedic Hospital from October 2020 to September 2022. All patients had extensive skin and subcutaneous soft tissue defects in the lower leg and received free anterolateral thigh flap repair with the medial gastrocnemius artery as the recipient artery. The skin of donor site was directly sutured. Results All 11 free skin flap survived in 11 patients, and both the donor and recipient sites healed in stage I. All patients were followed up after discharge, with a follow-up time of 12 to 35 months. The follow-up results at 12 months postoperatively showed good wound healing, good flap appearance and elasticity, restoration of normal knee and ankle joint function, and independent living ability. The donor site wounds healed well without significant scar hyperplasia. At the last follow-up, the flap sensory function was graded as S₃ in 2 patients and S₂ in 9 patients. The functional score of the affected limb was excellent in 5 patients and good in 6 patients, with an excellent and good rate of 100%. Conclusion The medial gastrocnemius artery has a suitable vessel caliber for anastomosis and a constant location. The use of the free anterolateral thigh flap with this artery as the recipient artery for the repair of severe wounds in the lower leg can effectively cover soft tissue defects and avoid injuring the residual main vessels in the lower leg, resulting in satisfactory outcomes.

Objective:To explore the clinical effects of free anterolateral thigh perforator flap pedicled with descending genicular artery in repairing wounds after lower leg limb-sparing surgery.Methods:A retrospective observational study was conducted. From January 2019 to June 2021, 12 patients with wounds after lower leg limb-sparing surgery who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 6 males and 6 females, aged 17 to 74 years, with original wound area ranging from 17 cm×9 cm to 40 cm×15 cm. Five patients had infection in wounds. The wounds were all repaired by free anterolateral thigh perforator flap from contralateral thigh, with area of 18 cm×10 cm to 37 cm×9 cm. The artery of flap was anastomosed with the descending genicular artery, and the wounds in donor areas were sutured directly. Seven patients were transplanted with split-thickness skin grafts from the contralateral thigh to cover the remaining wounds that can not be covered by flap and the wounds in donor areas were covered with gauze. During the operation, the types of perforating branch carried by flap and the types of arteries and veins in recipient areas were recorded. The survival and occurrence of vascular crisis of flap, the survival of skin graft, the wound healing in donor and recipient areas, and the length of hospital stay after flap transplant surgery were recorded. During follow-up, the color and texture of flap, reinfection in lower leg, and fracture healing were recorded. At the last follow-up, the limb salvage function of patients was evaluated according to the functional evaluation criteria of Chen Zhongwei's amputated limb replantation.Results:The types of perforating branches carried by flaps were as follows: 6 cases of only carrying the descending branch of the lateral circumflex femoral artery, 3 cases of only carrying the oblique branch of the lateral circumflex femoral artery, and 3 cases of carrying the descending branch of the lateral circumflex femoral artery and oblique branch of the lateral circumflex femoral artery after internal pressurization anastomosis. The types of arteries in the recipient area of flap were as follows: one case of main trunk of the descending genicular artery, 8 cases of the saphenous branch of the descending genicular artery, and 3 cases of the articular branch of the descending genicular artery. The types of veins in the recipient area of flap were as follows: 8 cases of one accompanying vein of the descending genicular artery and one branch of the great saphenous vein, and 4 cases of two branches of the great saphenous vein. All the flaps survived without vascular crisis, and all the skin grafts also survived. The wounds in the donor and recipient areas were all healed. The length of hospital stay of patient after flap transplant surgery ranged from 13 to 79 days. During the follow-up of 6 to 23 months, the color and texture of flap were both good, with no infection in lower leg wound. Internal or external fixation were removed after fracture healing in 5 patients, and bone graft internal fixation was performed in 7 patients whose fractures were not healed after surgery and all the incisions healed without infection. At the last follow-up, the limb salvage effect of patients was evaluated as followings: excellent in 7 patients, good in 4 patients, and fair in one patient.Conclusions:Free anterolateral thigh flap pedicled with descending genicular artery can effectively repair the wounds after lower leg limb-sparing surgery and control infection with short length of hospital stay, while not increasing the risk of secondary injury of distal limb vessels. Thus, it can obtain satisfactory limb salvage effect which is worthy of clinical promotion.

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.
Plant Breeding ; China ; Plant Roots/chemistry* ; Brain ; Publications

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.
China ; Drugs, Chinese Herbal ; Humans ; Industry ; Medicine, Chinese Traditional ; Policy

Objective: To explore the application value of T lymphocyte subsets combined with procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and white blood cell count (WBC) in the auxiliary diagnosis and prognosis evaluation of sepsis. Methods: In a retrospective study, seventy-two patients with sepsis diagnosed and treated in Tianjin First Central Hospital from June 2018 to April 2021 were selected as the research objects, and included in the sepsis group were 46 males and 26 females, aged 68 (57.3, 80.3) years. In addition, 111 patients with local infection admitted to hospital during the same period were included in the local infection group, including 62 males and 49 females, aged 68 (51, 77) years. Sepsis patients were divided into survival group (43 cases) and death group (29 cases) according to the 28-day outcome. CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺ ratio were detected by flow cytometry within 24 h after admission, PCT was detected by ELISA, CRP was detected by immunoturbidimetry, blood routine examination, blood lactic acid (Lac) and oxygen partial pressure (PO₂) were detected by instrumental method. Multivariate Logistic regression analysis was used to evaluate the correlation between each indicator and sepsis, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of each indicator for sepsis. Multivariate Logistic regression analysis and Kaplan Meier survival analysis were used to evaluate the prognostic value of each index for patients with sepsis. Results: Peripheral blood CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺ ratio and PLT in sepsis group were significantly lower than those in local infection group(Z=-8.184,P<0.001;Z=-7.210,P<0.001;Z=-5.936,P<0.001;Z=-2.700,P=0.007;Z=-6.381,P<0.001); PCT, CRP, NLR and Lac levels were significantly higher than those in local infection group(Z=-8.262,P<0.001;Z=-3.094,P=0.002;Z=-9.004,P<0.001;Z=-4.770,P<0.001). Multivariate Logistic regression model showed that PCT, NLR, CD3⁺, CD8⁺, CD4⁺/CD8⁺ were independent risk factors for sepsis. According to ROC curve analysis, AUC of sepsis patients diagnosed by each indicator were 0.862, 0.894, 0.858, 0.760 and 0.618, respectively. The cut-off values were 3.075 ng/ml, 10.715, 44.935×10⁹/L, 27.463×10⁹/L and 0.750, respectively. The NLR sensitivity was 80.6%, and the CD3⁺ specificity was 94.6%. The AUC of combined detection of PCT and NLR was 0.947, sensitivity was 87.5% and specificity was 91.9%. The combined detection AUC of PCT, NLR, CD3⁺, CD4⁺/CD8⁺ was 0.958, the sensitivity and specificity were 90.3% and 91.0% respectively(P<0.001). PCT and Lac in death group were significantly higher than those in survival group(Z=-2.302,P=0.021;Z=-3.095,P=0.002);Peripheral blood CD4⁺/CD8⁺ levels were significantly lower than those in survival group(Z=-3.691,P<0.001),Multivariate Logistic regression model showed that CD4⁺/CD8⁺ ratio was an independent risk factor for 28 d mortality in patients with sepsis (P<0.001). The ROC curve showed that the AUC was 0.758, and the Youden index reached the maximum when the cut-off value was 1.27, the sensitivity and specificity were 79.3% and 60.5%, respectively. Compared with patients with CD4⁺/CD8⁺ ≥1.27, 28-day mortality was significantly increased in patients with CD4⁺/CD8⁺<1.27 (P=0.032). Conclusion: The combined detection of PCT, NLR, CD3⁺ and CD4⁺/CD8⁺ can improve the auxiliary diagnostic efficiency of sepsis, and the ratio of CD4⁺/CD8⁺ in peripheral blood may have certain predictive value for the prognosis of sepsis.
Aged ; C-Reactive Protein/analysis* ; Female ; Humans ; Male ; Middle Aged ; Procalcitonin ; Retrospective Studies ; Sepsis/diagnosis* ; T-Lymphocyte Subsets/chemistry*

Objective:To study the clinical value of N-terminal pro-B-type natriuretic peptide (NTproBNP) predicting the risk of bronchopulmonary dysplasia (BPD) in very/extremely low birth weight infants (VLBWI/ELBWI).Methods:From June 2017 to December 2019, VLBWI/ELBWI admitted to neonatal department in our hospital were enrolled in this non-interventional prospective study. According to the occurrence of BPD, the infants were assigned into BPD group and non-BPD group. Infants in BPD group were further assigned into mild, moderate and severe BPD groups. Plasma NTproBNP were measured on 14 d, 21 d, 28 d, 35 d, 42 d and 49 d after birth. Repeated-measures ANOVA was used to determine the differences of NTproBNP at different time points in each group.Results:A total of 190 infants were enrolled, including 36 cases in BPD group (18, 13 and 5 cases in mild, moderate and severe BPD group, respectively) and 154 cases in non-BPD group. The gestational age, birth weight and 5-min Apgar score in BPD group were lower than non-BPD group. BPD group had significantly higher incidences of retinopathy of prematurity, patent ductus arteriosus and necrotizing enterocolitis and significantly longer duration of invasive mechanical ventilation and noninvasive ventilation than non-BPD group ( P<0.05).No significant differences existed in NTproBNP levels between BPD group and non-BPD group on 42 d and 49 d ( P>0.05). At other time points, NTproBNP levels in BPD group were significantly higher than non-BPD group ( P<0.05). NTproBNP level in severe BPD group was the highest on 14 d. No significant differences existed in NTproBNP levels between mild and moderate groups on 28 d ( P>0.05). At other time points, NTproBNP in severe BPD group was higher than mild and moderate BPD groups ( P<0.001). The receiver operating characteristic curve analysis showed the best cut-off value of NTproBNP was 982 pg/ml on 14 d (AUC=0.907, 95% CI 0.831~0.983). Conclusions:VLBWI/ELBWI with BPD have higher levels of NTproBNP. And the more severe of BPD, the higher the NTproBNP level. NTproBNP has certain predictive values for BPD in VLBWI/ELBWI.

Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.