ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Humans ; COVID-19 ; HIV Infections/drug therapy* ; Risk Factors

Abstract Plant exocrine-like nanovesicles(PELNs) is a new nano-therapeutic agent and delivery platform, which not only has the potential for disease treatment, but also can be used as a drug carrier to target disease sites and play a dual role in treatment and delivery. More importantly, PELNs has the characteristics of green nature and low immunogenicity. This review systematically introduced several secretory mechanisms of PELNs:Outer capsule positive organelle, polyvesicular body, vacuole and autophagosome; three components such as lipid, protein and nucleic acid; centrifugation, ultrafiltration, size exclusion chromatography, flow field-flow fractionation, immunomagnetic beads, polymer precipitation and other separation methods and their biological functions such as anti-inflammation, anti-tumor, protection of regeneration, antivirus, liver protection, etc.; sorted out the potential mechanism of PELNs as a therapeutic agent and molecular delivery platform, and put forward the problems existing in the research process of PELNs, such as quantification, mechanism research and few clinical trials. And its development potential in the future is discussed.

Seed quality plays an important role in the agricultural and animal husbandry production, the effective utilization of genetic resources, the conservation of biodiversity and the restoration and reconstruction of plant communities. Seed aging is a common physiological phenomenon during storage. It is a natural irreversible process that occurs and develops along with the extension of seed storage time. It is not only related to the growth, yield and quality of seed and seedling establishment, but also has an important effect on the conservation, utilization and development of plant germplasm resources. The physiological mechanisms of seed aging are complex and diverse. Most studies focus on conventional physiological characterization, while systematic and comprehensive in-depth studies are lacking. Here we review the recent advances in understanding the physiology of seed aging process, including the methods of seed aging, the effect of aging on seed germination, and the physiological and molecular mechanisms of seed aging. The change of multiple physiological parameters, including seed vigor, electrical conductivity, malondialdehyde content and storage material in the seed, antioxidant enzyme activity and mitochondrial structure, were summarized. Moreover, insights into the mechanism of seed aging from the aspects of transcriptome, proteome and aging related gene function were summarized. This study may facilitate the research of seed biology and the conservation and utilization of germplasm resources.
Germination ; Plants ; Proteome ; Seedlings ; Seeds/genetics*

Objective:To investigate the clinical value of stylized laparoscopic hemicolec-tomy for left colon cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 174 patients who underwent laparoscopic hemicolectomy for left colon cancer in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 106 males and 68 females, aged 59(range, 17?86)years. All patients underwent stylized laparoscopic hemicolectomy for left colon cancer. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative histopathological examinations; (4) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect tumor recurrence and metastasis and survival of patients up to October 2021. Follow-up was performed once every 3 months within postoperative 2 years, once every 6 months within postoperative 2 to 5 years and once a year after postoperative 5 years, with the end point as tumor recurrence and metastasis or death of patients. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3). Count data were described as absolute numbers or percentages. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Results:(1) Surgical situations. All the 174 patients underwent stylized laparoscopic hemicolectomy for left colon cancer successfully, including 6 cases receiving preoperative enteral stent placement due to bowel obstruc-tion, 3 cases receiving defunctioning ileostomy and 1 case receiving Hartmann procedure. The operation time, volume of intraoperative blood loss, time to postoperative initial defecation and duration of postoperative hospital stay of the 174 patients were 97(80,106)minutes, 45(25,60)mL, 5(3,6)days and 7(6,8)days, respectively. (2) Postoperative complications. Twelve of the 174 patients had complications, including 4 cases with incision infection or fat liquefaction, 3 cases with anastomotic leakage, 2 cases with incomplete bowel obstruction, 1 case with abdominal hemo-rrhage, 1 case with chylous leakage and 1 case with pulmonary infection. The 2 cases with anastomotic leakage underwent ileostomy. The patient with abdominal hemorrhage underwent laparotomy to stop bleeding. One elder patient died of postoperative pulmonary infection. The other patients with complications recovered with conservative treatment. (3) Postoperative histopatho-logical examinations. Of the 174 patients, there were 27 cases in stage Ⅰ of TNM staging, 68 cases in stage Ⅱ, 77 cases in stage Ⅲ and 2 cases in stage Ⅳ. There were 9 cases with well differentiated tumor, 107 cases with moderately differentiated tumor and 58 cases with poorly differentiated tumor. The number of lymph node detected, the number of positive lymph node and tumor diameter of the 174 patients were 19(15,23), 0(0,2) and 4(3,5)cm, respectively. Of the 174 patients, there were 79 cases with lymph node metastases, 21 cases with cancerous nodules, 35 cases with vascular invasion and 29 cases with nerve invasion. (4) Follow-up. Of the 174 patients, 157 cases were followed up for 27(range, 1?70)months. Of the 157 patients who conducted follow-up, 20 cases had tumor metastasis, including 9 cases with multiple metastasis, 5 cases with liver metastasis, 4 cases with lung metastasis, 1 case with bone metastasis and 1 case with spleen metastasis. The 5-year overall survival rate and tumor free survival rate of the 157 patients were 90.9% and 80.8%, respectively.Conclusion:The stylized laparoscopic hemicolectomy for left colon cancer is safe and feasible.

Objective:To investigate the characteristics of No.253 lymph node metastasis in middle and low rectal cancer and its influencing factors.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 316 patients with middle and low rectal cancer who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2013 to October 2021 were collected. There were 1 339 males and 977 females, aged (61±12)years. All patients underwent D 3 radical surgery for rectal cancer. Observation indicators: (1) No.253 lymph node metastasis in patients with middle and low rectal cancer; (2) analysis of influencing factors for No.253 lymph node metastasis in patients with middle and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD. Count data were expressed as absolute numbers and percentages, and comparison between groups was performed by the chi-square test. Logistic regression model was used for multivariate analysis. Results:(1) No.253 lymph node metastasis in patients with middle and low rectal cancer. There were 128 of 2 316 patients with positive No.253 lymph node and 2 188 cases with negative No.253 lymph node. The No.253 lymph node metastasis rate was 5.527%(128/2 316). There were 568 of 2 316 patients with the distance from distal margin of tumor to anal margin as 8?10 cm, 766 cases as ≥6 cm and<8 cm, 982 cases as <6 cm. Of the 568 patients with the distance from distal margin of tumor to anal margin as 8?10 cm, 57 cases had positive No.253 lymph node, including 3 cases(5.263%) of high differentiated tumor, 9 cases(15.789%) of moderate differentiated tumor, 45 cases(78.948%) of low differentiated tumor, respectively. There was 0 case of the above 57 patients with positive No.253 lymph node in TNM stage Ⅰ, 0 case in TNM stage Ⅱ, 20 cases(35.088%) in TNM stage Ⅲ, 37 cases(64.912%) in TNM stage Ⅳ, respectively. Of the 766 patients with the distance from distal margin of tumor to anal margin as ≥6 cm and <8 cm, 42 cases had positive No.253 lymph node, including 4 cases(9.524%) of high differentiated tumor, 11 cases(26.190%) of moderate differentiated tumor, 27 cases(64.286%) of low differentiated tumor, respectively. There was 0 case of the above 42 patients with positive No.253 lymph node in TNM stage Ⅰ, 0 case in TNM stage Ⅱ, 19 cases(45.238%) in TNM stage Ⅲ, 23 cases(54.762%) in TNM stage Ⅳ, respectively. Of the 982 patients with the distance from distal margin of tumor to anal margin as <6 cm, 29 cases had positive No.253 lymph node, including 1 case (3.448%) of high differentiated tumor, 3 cases (10.345%) of moderate differentiated tumor, 25 cases (86.207%) of low differentiated tumor, respectively. There was 0 case of the above 29 patients with positive No.253 lymph node in TNM stage Ⅰ, 0 case in TNM stage Ⅱ, 12 cases(41.379%) in TNM stage Ⅲ, 17 cases(58.621%) in TNM stage Ⅳ, respectively. (2) Analysis of influencing factors for No.253 lymph node metastasis in patients with middle and low rectal cancer. Results of univariate analysis showed that tumor T staging, tumor N staging, tumor TNM staging, tumor differentiation degree, the distance from distal margin of tumor to anal margin were related factors for No.253 lymph node metastasis in patients with middle and low rectal cancer ( χ2=28.48, 44.58, 172.62, 227.67, 34.57, P<0.05). Results of multivariate analysis showed that tumor T staging as stage T4, tumor N staging as stage N2, tumor TNM staging as stage Ⅳ, low differentiated tumor, the distance from distal margin of tumor to anal margin as ≥6 cm and <8 cm, 8?10 cm were independent risk factors for No.253 lymph node metastasis in patients with middle and low rectal cancer ( odds ratio=2.74, 3.48, 10.72, 21.47, 1.92, 3.67, 95% confidence intervals as 1.91?3.92, 2.42?4.98, 7.36?15.62, 10.33?44.60, 1.27?2.91, 2.31?5.81, P<0.05). Conclusions:The risk of No.253 lymph node metastasis is relatively high in middle and low rectal cancer patients with long distance from distal margin of tumor to anal margin, low differentiated tumor, and in high TNM stages. Tumor T staging as stage T4, tumor N staging as stage N2, tumor TNM staging as stage Ⅳ, low differentiated tumor, the distance from distal margin of tumor to anal margin as ≥6 cm and <8 cm, 8?10 cm are independent risk factors for No.253 lymph node metastasis in patients with middle and low rectal cancer.

Objective:To study the clinical features and drug resistance profile of neonatal sepsis caused by different species of Klebsiella.Methods:From January 2009 to December 2018, cryopreserved Klebsiella strains from blood culture of neonatal sepsis cases in NICU of our hospital were reactivated. Molecular identification and antimicrobial susceptibility tests were performed. Clinical features, laboratory tests, drug resistance profile and prognosis of these patients were analyzed retrospectively.Results:A total of 29 strains of Klebsiella were reactivated. Molecular identification assigned 22 cases (75.9%) into Klebsiella pneumoniae (Kpn) group and 7 cases (24.1%) into Klebsiella quasipneumoniae (Kqu) group. Gestational age and birth weight of Kpn group were higher than Kqu group [(33.1±3.2) weeks vs. (30.6±0.9) weeks, (1 847±677) g vs. (1 416±121) g] ( P<0.05). Abdominal distension was more common in Kqu group than Kpn group [42.9% (3/7) vs. 4.5% (1/22), P<0.05]. No significant differences existed in the laboratory tests including white blood cell count, platelet count, hypersensitive C-reactive protein and procalcitonin between the two groups ( P>0.05). Kpn was 100.0% sensitive to Cefazolin-Tazobactam and Amikacinto and less sensitive to Imipenem and Cefperazone-Sulbactam, Meropenem and Ertapenem. Kqu was generally more sensitive than Kpn and the sensitivity of Kqu to Imipenem was 100.0%. No significant differences existed of the prognosis between the two groups ( P>0.05). Conclusions:Kpn is the main pathogen of neonatal Klebsiella sepsis. Kqu sepsis is more common in neonates with smaller gestational age and lower birth weight. Abdominal distention is common presenting symptom in Kpn sepsis and sensitive antibiotics should be used early.

Objective:To explore the potential biomarkers for the metastasis and prognosis of uveal melanoma (UM) from molecular genetics.Methods:The data of 80 UM samples including 18 metastatic cases and 62 non-metastatic cases between 2007 and 2019 were downloaded from The Cancer Genome Atlas database.The tumor mutation burden and gene mutation information, including mutant genes, variant type, the proportion of single nucleotide variation (SNV) and mutation proportion, were analyzed using maftools package in R software, and the differentially expressed genes (DEGs) between the two groups were screened using edgeR package.The Kyoto Encyclopedia of Genes and Genomes enrichment analysis based on the DEGs was performed to screen prognosis-associated genes using KOBAS.Cox regression model was established using survival package in R software to verify the association between gene mutation and DEGs and the prognosis of UM patients.Results:The mutation analysis showed that missense mutation accounted for a large proportion in the mutation of UM samples, and the main variant type was SNV, and the mutation burden of UM was low.Compared with the non-metastatic UM samples, 562 DEGs were identified in the metastatic UM samples.Three pathways, including vitreoretinal degeneration, proteoglycans in cancer, and PI3K-Akt pathway, were significantly enriched.The expression levels of BAP1, FOXO3 and ITPR2 were 2 982.50 (1 251.50, 5 637.00), 1 223.00 (914.75, 2 706.25) and 2 201.50 (570.75, 4 814.00)in the metastatic group, and 5 225.00 (2 281.25, 8 784.00), 2 293.50 (1 254.25, 3 693.75) and 474.00 (153.00, 1 437.75) in the non-metastatic group, respectively.The expression of BAP1 and FOXO3 among the DEGs were significantly down-regulated and ITPR2 expression was significantly up-regulated in the metastatic group in comparison with the non-metastatic group ( Z=-1.786, -1.982, -3.065; all at P<0.10). The survival analysis revealed BAP1 mutation, decreased FOXO3 expression and increased ITPR2 expression were associated with inferior survival of UM patients (all at P<0.10). Conclusions:BAP1 mutation, up-regulation of FOXO3 and down-regulation of ITPR2 might be potential biomarkers for the metastasis and prognosis of UM.