Objective:To investigate the incidence of cervical metastasis of oral and maxillary squamous cell carcinoma(SCC)and to define its impact factors.Methods:A retrospective study of patients with SCC of hard palate and maxillary alveolus treated by surgery from 2002 to 2011.Results:The incidences of cervical metastasis and occult metastasis were 17.2%(11 /64)and 9.8%(5 /51)re-spectively.pT classification and vascular invasion were correlated with cervical metastasis.Occult metastatic risk was significantly higher in pT4 patients.Presence of positive nodes impaired prognosis significantly.Conclusion:Overall and occult metastasis of oral and maxillary SCC were highly associated with pT classification.Routine and synchronous elective neck dissection(END)is recomend for the treatment of T4 lesions while observation is alternative for T1 -T3 lesions.

WRKY transcription factors, one of the largest families of transcriptional regulators in plants, involve in multiple life activities including plant growth and development as well as stress responses. However, little is known about the types and functions of WRKY transcription factors in Catharanthus roseus, an important medicinal plant. In this study, we identified 47 CrWRKY transcriptional factors from 26 009 proteins in Catharanthus roseus, and classified them into three distinct groups (G1, G2 and G3) according to the structure of WRKY domain and evolution of the protein family. The expression profiling showed that these CrWRKY genes expressed in a tissue/organ specific manner. The 47 CrWRKY genes were clustered into three types of expression patterns. The first type includes the CrWRKYs highly expressed in flowers and the protoplast treated with methy jasmonate (MeJA) or yeast extraction (YE). The second type contains the CrWRKYs highly expressed in stem and hairy root. The third type represents the CrWRKYs highly expressed in root, stem, leaf, seedling and the hairy root treated by MeJA. Real time quantitative PCR was employed to further identify the expression patterns of the 16 selected CrWRKY genes in various organs, the MeJA-treated protoplasts and hairy roots of Catharanthus roseus, and similar results were obtained. Notably, the expresion of more than 1/3 CrWRKY genes were regulated by MeJA or YE, indicating that these CrWRKYs are likely involed in the signalling webs which modulate the biosynthesis of terpenoid indole alkaloid and plant responses to various stresses. The present results provide a framework for functional identification of the CrWRKYs and understanding of the regulation network of terpenoid indole alkaloid biosynthesis in Catharanthus roseus.
Amino Acid Sequence ; Catharanthus ; genetics ; metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; Molecular Sequence Data ; Plant Proteins ; biosynthesis ; genetics ; Plants, Medicinal ; genetics ; metabolism ; Transcription Factors ; biosynthesis ; genetics

Palmitoleic acid (16:1delta9), an unusual monounsaturated fatty acid, is highly valued for human nutrition, medication and industry. Plant oils containing large amounts of palmitoleic acid are the ideal resource for biodiesel production. To increase accumulation of palmitoleic acid in plant tissues, we used a yeast (Saccharomyees cerevisiae) acyl-CoA-delta9 desaturase (Scdelta9D) for cytosol- and plastid-targeting expression in tobacco (Nicotiana tabacum L.). By doing this, we also studied the effects of the subcellular-targeted expression of this enzyme on lipid synthesis and metabolism in plant system. Compared to the wild type and vector control plants, the contents of monounsaturated palmitoleic (16:1delta9) and cis-vaccenic (18:1delta11) were significantly enhanced in the Scdelta9D-transgenic leaves whereas the levels of saturated palmitic acid (16:0) and polyunsaturated linoleic (18:2) and linolenic (18:3) acids were reduced in the transgenics. Notably, the contents of 16:1delta9 and 18:1delta11 in the Scdelta9D plastidal-expressed leaves were 2.7 and 1.9 folds of that in the cytosolic-expressed tissues. Statistical analysis appeared a negative correlation coefficient between 16:0 and 16:1delta9 levels. Our data indicate that yeast cytosolic acyl-CoA-delta9 desaturase can convert palmitic (16:0) into palmitoleic acid (16:1delta9) in high plant cells. Moreover, this effect of the enzyme is stronger with the plastid-targeted expression than the cytosol-target expression. The present study developed a new strategy for high accumulation of omega-7 fatty acids (16:1delta9 andl8:1delta11) in plant tissues by protein engineering of acyl-CoA-delta9 desaturase. The findings would particularly benefit the metabolic assembly of the lipid biosynthesis pathway in the large-biomass vegetative organs such as tobacco leaves for the production of high-quality biodiesel.
Fatty Acid Desaturases ; genetics ; metabolism ; Fatty Acids, Monounsaturated ; metabolism ; Plants, Genetically Modified ; Recombinant Proteins ; genetics ; metabolism ; Saccharomyces cerevisiae ; enzymology ; Saccharomyces cerevisiae Proteins ; genetics ; metabolism ; Tobacco ; genetics ; metabolism

Objective The bispectral index (BIS) was introduced into the sedation strategy of critical patients in intensive care unit (ICU) and replaced the Richmond agitation sedation scale (RASS).The ventilation time,ICU length of stay,and 90-day mortality were compared between the two groups of patients who performed early goal-directed sedation (EGDS) or standard traditional directed sedation (STDS) strategies.Methods A prospective controlled study of severe patients with mechanical ventilation ≥48 h in ICU (20 cases from April 2016 to May 2017,46 cases from June 2017 to April 2018) were randomly divided into EGDS or STDS group.There were no significant differences in age,gender,and acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ) score between the two groups in the two periods.The correlation between RASS and BIS was analyzed in the first period.The BIS of the patients in a RASS range of (-2-1) was 73.65 ± 7.87 in the EGDS group,and that of RASS range of (-3--1) was 64.14 ± 7.25 in the STDS group.The above BIS was applied to the two sedation strategies in the second period respectively.The ventilation time,ICU length of stay,and 90-day mortality were recorded.Results There was no significant difference in the ventilation time between the two groups [(164.12 ± 137.96) h and (155.33 ±64.86)h,P =0.08].ICU length of stay of the EGDS group was longer than that of the STDS group.The 90-day mortality of the EGDS group was higher than that of the STDS group.Conclusions Correlations between RASS and BIS were found in this study,and BIS can be used for sedation assessment in ICU patients.Large sample study is still needed to compare EGDS and STDS with BIS.

Objective To investigate the safety and efficacy of endoscopic varices ligation(EVL) plus endoscopic varices sclerotherapy(EVS)for esophageal varices hemorrhage in patients with liver cirrhosis. Methods Fifty?two liver cirrhosis patients with esophageal varices bleeding were randomly divided into EVL group(n=24)and EVLS group(n=28)according to random numbers generated by computer after first EVL. The EVL group continued undergoing EVL, and the EVLS group was treated by EVS. The interval of treatment was 2 weeks till varices disappeared. All patients were followed up for 18 months with endoscopy and endoscopic ultrasonography(EUS). The efficacy,changes of esophageal varices and perforating veins, varices recurrence and rebleeding were observed. Results There was no significant difference of complete cure rate between EVLS group and EVL group[67.9%(19/28)VS 62.5%(15/24),P>0.05]. The mean session of treatment(2.68±1.0 VS 1.83±0.7,P<0.05), and perforating veins obliteration rate after treatment in EVLS group was higher than that in EVL group[70.8%(17/24)VS 23.8%(5/21),P<0.05]. During 18 months of follow?up,there was no significant difference of rebleeding rate between the two groups[3.6%(1/28)VS 12.5%(3/24),P>0.05],and the varices recurrence rate was higher in EVL group than that in EVLS group[77.3%(17/22)VS 44.0%(11/25), P<0.05]. Child?Pugh class B patients in EVL group had a higher varices recurrence rate compared to that in EVLS group[75.0%(9/12)VS 31.5%(5/16), P<0.05]. Endoscopic recurrences occurred in patients with non?occlusive perforating veins. Conclusion EVL plus EVS sequential procedure is safe and effective for treatment of esophageal varices hemorrhage,especially for Child?Pugh class B patients.Perforating veins may play a key role in the development of esophageal varices and recurrence after endoscopic therapy. EUS findings can direct the endoscopic therapy and predict the variceal recurrence.

Objective:To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10 6/kg. Results:①All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. ②Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively.Conclusion:The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

In order to investigate the molecular mechanism of silk/threonine protein kinase (STK)-mediated blue light response in the algal Chlamydomonas reinhardtii, phenotype identification and transcriptome analysis were conducted for C. reinhardtii STK mutant strain crstk11 (with an AphvIII box reverse insertion in stk11 gene coding region) under blue light stress. Phenotypic examination showed that under normal light (white light), there was a slight difference in growth and pigment contents between the wild-type strain CC5325 and the mutant strain crstk11. Blue light inhibited the growth and chlorophyll synthesis in crstk11 cells, but significantly promoted the accumulation of carotenoids in crstk11. Transcriptome analysis showed that 860 differential expression genes (DEG) (559 up-regulated and 301 down-regulated) were detected in mutant (STK4) vs. wild type (WT4) upon treatment under high intensity blue light for 4 days. After being treated under high intensity blue light for 8 days, a total of 1 088 DEGs (468 upregulated and 620 downregulated) were obtained in STK8 vs. WT8. KEGG enrichment analysis revealed that compared to CC5325, the crstk11 blue light responsive genes were mainly involved in catalytic activity of intracellular photosynthesis, carbon metabolism, and pigment synthesis. Among them, upregulated genes included psaA, psaB, and psaC, psbA, psbB, psbC, psbD, psbH, and L, petA, petB, and petD, as well as genes encoding ATP synthase α, β and c subunits. Downregulated genes included petF and petJ. The present study uncovered that the protein kinase CrSTK11 of C. reinhardtii may participate in the blue light response of algal cells by mediating photosynthesis as well as pigment and carbon metabolism, providing new knowledge for in-depth analysis of the mechanism of light stress resistance in the algae.
Chlamydomonas reinhardtii/genetics* ; Photosynthesis/genetics* ; Plants/metabolism* ; Protein Kinases ; Threonine/metabolism* ; Carbon/metabolism* ; Serine/metabolism*