SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To study the insulin-like growth factors-1 (IGF-1) and lipid level of term small for gestational age (SGA) infants within 24 hours postnatally and to explore the correlation between IGF-1 and blood lipids.Methods:A prospective study was conducted on singleton term SGA and appropriate for gestational age infant (AGA) who were delivered and admitted to the neonatal ward of Guangdong Women and Children Hospital within 24 hours after birth from May 2020 to January 2021, and the infants were divided into SGA and AGA groups to compare the differences in IGF-1 and lipid levels within 24 hours after birth and to analyze the correlation between IGF-1 and lipids.Results:A total of 95 cases in the SGA group and 84 cases in the AGA group were included in the study. The proportion of infants with IGF-1 <25 ng/ml was significantly higher in SGA group (87.4%) than in the AGA group (52.4%). It was also found that the proportion of infants with IGF-1 <25 ng/ml in SGA was significantly higher than that in AGA within different gender composition groups, early-term and full-term births groups. The triglyceride (TG) level was higher in the SGA group than that in the AGA group, but the high-density lipoprotein cholesterol (HDL-C) level was lower than that in the AGA group ( P<0.05). IGF-1 level within 24 hours postnatally in SGA and AGA was positively correlated with HDL-C levels ( P<0.01) and negatively correlated with TG ( P<0.01), and HDL-C level was a predictor of IGF-1. Conclusions:Compared with term AGA, SGA term infants showed insufficient IGF-1 and HDL-C secretion and high TG within 24 hours after birth. Nutritional support for SGA should be given promptly after birth to avoid hypoglycemia and to stimulate IGF-1 secretion.

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

A chemical fingerprint is an important mean for quality control of traditional Chinese medicine (TCM); however, there is much redundant information in a conventional fingerprint that can affect its availability and accuracy. In this work, the antibacterial biopotency of Scutellariae Radix (Huangqin, HQ) was determined according to the parallel line method of quantitative response. HPLC was adopted to detect the chemical fingerprint of HQ; Grey relational analysis (GRA) was used to identify the primary effective components. The results showed that the antibacterial biopotency of 15 batches of HQ ranged from 0 to 1 000 U·g^-1 and the average potency was 556.29 ± 258.57 U·g^-1 (1 U is equivalent to the bacteriostatic activity of 2.25 μg gentamicin). There were 34 characteristic peaks in the fingerprints of the samples and their similarities were 0.255-0.991. Eight components (P33, P30/baicalein, P19/baicalin, P15, P29, P34, P31/wogonin and P28) are positively related to antibacterial biopotency and selected from the top ten components of the grey correlation sequence to define the antibacterially effective components fingerprint of HQ. This fingerprint can clearly distinguish the commodity specification and grade, and can also characterize the morphology, components and the bacteriostatic potency differences of HQ. In summary, we established an antibacterially effective components fingerprint which provides simplified information on the antibacterial activity of Scutellariae Radix and could significantly improve the efficacy, specificity, and discriminative ability of the fingerprint for HQ, and could be a useful reference for the comprehensive quality evaluation of other TCM.

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.

Traditional Chinese medicine (TCM) Xiaoaiping shows a pharmacological activity in treatment of breast cancer. Although neoadjuvant chemotherapy has been more and more widely used in treatment of breast cancer in recent years, no report has been made about the clinical efficacy and mechanism of the combined application of neoadjuvant chemotherapy and Xiaoaiping in treatment of breast cancer. In this study, 66 patients with breast cancer were selected and divided into the control group and the treatment group evenly with the random number table method. All patients received TEC neoadjuvant chemotherapy. On that basis, the treatment group also received the adjuvant therapy of Xiaoaiping injection (60 mL, i. v. , qd). The short-term response rate and the follow-up survival rate of the two groups were observed and compared. Surgical specimens of the patient were collected to observe and compare their expressions of estrogen receptor ER-α36 in breast cancer tissues with the immunohistochemical method. According to the findings, the overall response rate of the treatment group was 78.79%, which was significantly higher than that of the control group (57.58% , χ2 = 5.48, P < 0.05). Compared with the control group, the treatment group showed significant increases in the disease-free survival (DFS) rate and the total survival rate at the 3rd year and 5th year (all P < 0.05) , and a notable reduction in ER-α36 expression in breast cancer tissues (P < 0.05). Based on the our results, Xiaoaiping can significantly enhance short-term ad long-term efficacies of neoadjuvant chemotherapy for breast cancer. Its mechanism may be correlated with the inhibition of ER-α 36 expression in breast cancer tissues.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; mortality ; Combined Modality Therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Treatment Outcome

Many phytochemicals show promise in cancer prevention and treatment, but their low aqueous solubility, poor stability, unfavorable bioavailability, and low target specificity make administering them at therapeutic doses unrealistic. This is particularly true for (-)-epigallocatechin gallate, curcumin, quercetin, resveratrol, and genistein. There is an increasing interest in developing novel delivery strategies for these natural products. Liposomes, micelles, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and poly (lactide-co-glycolide) nanoparticles are biocompatible and biodegradable nanoparticles. Those nanoparticles can increase the stability and solubility of phytochemicals, exhibit a sustained release property, enhance their absorption and bioavailability, protect them from premature enzymatic degradation or metabolism, prolong their circulation time, improve their target specificity to cancer cells or tumors via passive or targeted delivery, lower toxicity or side-effects to normal cells or tissues through preventing them from prematurely interacting with the biological environment, and enhance anti-cancer activities. Nanotechnology opens a door for developing phytochemical-loaded nanoparticles for prevention and treatment of cancer.
Antineoplastic Agents, Phytogenic ; administration & dosage ; therapeutic use ; Drug Carriers ; Humans ; Materials Testing ; Nanoparticles ; Neoplasms ; drug therapy ; Phytochemicals ; administration & dosage ; therapeutic use ; Plant Extracts ; administration & dosage ; therapeutic use

Axillary lymph nodes are the most common and initial site of metastasis of breast carcinoma. Precise axillary staging of breast carcinoma before initial treatment is crucial as it allows efficient identification for local and systemic treatment options, and provides prognostic information. Sentinel lymph node biopsy (SLNB) is an accurate minimally invasive technology for axillary staging. Although top evidence of high-quality clinical trials showed that SLNB could safely and effectively replace axillary lymph node dissection (ALND) for axillary negative patients with decrease in complications and improvement in quality of life, there are specific indications and contraindications for SLNB. Clinicians should balance the compliance of guideline and native clinical practice, especially for the circumstance of multifocal/multicentric lesion, breast biopsy history, and neoadjuvant chemotherapy. With the accumulation of clinical practice and new results of clinical trials, axillary therapy has changed from unique surgery to patient-tailored multi-disciplinary intervention, although ALND should be recommended traditionally if SLNB is positive. Intensive and accurate preoperative axillary staging is gradually valued by clinicians. Development of imaging modality especially ultrasonography and ultrasound-guided biopsy can identify some extra lymph node positive patients directly to ALND with avoidance of unnecessary SLNB. Thus, the positive rate of SLNB will decline significantly. It seems possible that axillary management will step into a noninvasive era abandoning SLNB in some patients with small breast cancer. In this article we review the prospect and guideline update of SLNB for patients with early-stage breast cancer.
Axilla ; Breast Neoplasms ; pathology ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Practice Guidelines as Topic ; Sentinel Lymph Node Biopsy

Objective To determine the risk factors for imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in neonatal intensive care unit (NICU).Methods One hundred and eighty-eight Pseudomonas aeruginosa infected children (confirmed by pathogenic examination) in the NICU of Maternal and Child Health Hospital of Guangdong from January 1,2008 to December 31,2011,were chosen as the objects of study,and were divided into two groups.The first group included 73 children that had been isolated with IRPA strains(IRPA group),and the second group included 115 children that only had imipenem-sensitive Pseudo monas aeruginosa (ISPA) strains (ISPA group).Chi-square test or t-test was applied.The risk factors were investigated by univariate or multivariate Logistic regression analysis.Results Data from univariate analysis showed that the gestational age and birth weight of neonates were lower than those in ISPA group [(34.0±3.5) weeks vs (35.6±2.8)weeks,t=3.413,P＜0.01; (1848.1±276.4) g vs (2110.7±345.6) g,t=5.472,P＜0.01].There were more neonates with gestational age ≤ 32 weeks [67.1％ (49/73) vs 45.2 ％ (52/115)],birth weight ＜1500 g [73.9％ (54/73) vs 33.0％(38/115)],small for gestational age [68.5％ (50/73) vs 29.6％ (34/115)],receiving imipenem [72.6％ (53/73) vs 27.0％ (31/115)] or the third generation cephalosporins [65.8％ (48/73) vs 33.0％ (38/115)] two weeks before the isolation of Pseudomonas aeruginosa,and mechanical ventilation [78.1％ (57/73) vs 61.7 ％ (71/115)],deep vein catheterization [83.6％(61/73) vs 65.2％(75/115)] in the IRPA group than in the ISPA group (all P＜0.05 or 0.01).The multivariate Logistic regression analysis revealed that imipenem treatment within two weeks before the isolation of Pseudomonas aeruginosa (OR=6.409; 95％ CI:1.926-21.333,P =0.002) was an independent risk factor.Conclusions IRPA infection in NICU hospitalized infants is strongly related to their gestational age and birth weight.History of imipenem administration could be an independent risk factor.

Adult ; Aged ; Chylothorax ; etiology ; therapy ; Female ; Humans ; Middle Aged ; Neck Dissection ; adverse effects ; Retrospective Studies ; Thyroid Neoplasms ; surgery