The Prognosis of Skip Metastasis in Papillary Thyroid Microcarcinoma Is Better Than That of Continuous Metastasis.

CONTEXT: A few papillary thyroid microcarcinomas (PTMCs) may have skip metastasis (SLNM), but the risk factors remain controversial and the prognosis is unclear. OBJECTIVES: To investigate the incidence, lymph node metastasis (LNM) patterns, risk factors, and prognosis of SLNM in PTMCs. METHODS: We reviewed the medical records of PTMC patients who underwent thyroid surgery in our institution. Analyses of risk factors were performed for SLNM. Recurrence-free survival (RFS) of SLNM, central lymph node metastasis (CLNM), and continuous metastasis (CLNM and lateral lymph node metastasis [CLNM + LLNM]) were compared after propensity score matching (PSM). RESULTS: SLNM was detected in 1.7% (50/3923) and frequently involved level III (66.7%). Compared with CLNM + LLNM, SLNM had more LNM at a single level (P < 0.01) and less LNM at 2 levels (P < 0.05). A tumor size of 0.5 to 1 cm (odds ratio [OR], 2.26; 95% CI, 1.27-4.00) and location in the upper pole (OR, 3.30; 95% CI, 2.02-5.40) were independent risk factors for SLNM. A total of 910 (23.2%) PTMCs with LNM were included in the prognostic analysis. At a median follow-up of 60 months, the RFS of SLNM did not differ from that of CLNM (P = 0.10) but was significantly higher than that of CLNM + LLNM (P < 0.01) after using PSM. CONCLUSIONS: When the tumor size is 0.5 to 1 cm or its location is in the upper pole, we must remain vigilant to SLNM in PTMC. Because its prognosis is comparable to that of only CLNM and better than that of CLNM + LLNM, less intensive treatment should be considered.

Long-term outcomes and prognostic factors in papillary thyroid microcarcinoma patients with distant metastases.

PURPOSES: Distant metastasis from papillary thyroid microcarcinoma (PTMC) is extremely rare and the long-term outcomes and independent prognostic factors remain unclear. The present study aimed to investigate clinicopathological characteristics and evaluate the long-term outcomes and prognostic factors of PTMC patients with distant metastases (DM) who underwent surgery and radioactive iodine (131I) treatment. METHODS: We retrospectively reviewed the medical records of 13,441 patients with thyroid cancer (including 1697 cases with PTMC) who underwent 131I treatment at our institution between January 2008 and December 2019. PTMC patients with distant metastases with sufficient clinical follow-up data were enrolled in this cohort study. The overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method and the prognostic factors were assessed by Cox proportional hazards. RESULTS: Thirty-three PTMC patients with DM were enrolled in this study. The median follow-up was 75 months (range: 5-151 months). The 5-year and 10-year OS rates were 96.97 and 81.41%, respectively, and the 5-year and 10-year PFS rates were 90.46 and 69.68%, respectively. Multivariate analysis showed that male sex (P = 0.005), radioactive iodine refractory PTMC (P = 0.033), and symptomatic DM (P = 0.022) were significantly associated with worse 10-year PFS in PTMC patients with DM. No independent predictor related to poor 10-year OS was found in the present study. CONCLUSIONS: The prognosis of PTMC patients becomes worse after the development of DM. Male sex, radioactive iodine refractory PTMC, and symptomatic DM were identified as independent factors associated with PFS.

Effects of Kuntai capsule on GnRH-a-induced perimenopause symptoms:a prospective randomized controlled study / 中国实用妇科与产科杂志

OBJECTIVE: To evaluate the effect of Kuntai capsule on the gonadotrophin releasing hormone agonist(GnRH-a)-induced perimenopaus symptoms and the sex hormone levels.METHODS: A total of 99 patients with uterine fibroids,adenomyosis or moderate to severe endometriosis who needed the treatment of GnRH-a at Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2015 to March 2016 were collected and randomly divided into research group(Kuntai capsule)and control group(Tibolone). GnRH-a was injected once every 28 days and first injection of GnRH-a was administered on the 2 nd to 4 th day of menstrual period or retraction bleeding after surgery.Kuntai capsule or Tibolone was orally taken beginning from the first GnRH-a injection,and the co-administration of Caltrate D-600 and alfacalcidol was given in both groups.The Kupperman scores,sex hormone levels including folliclestimulating hormone(FSH)and estrogen(E_2),and adverse events were recorded.RESULTS: Kuntai capsule kept the perimenopause symptoms at mild level with the slow increase of Kupperman scores,whose effect was significantly superior to Tibolone(P<0.05)after 8 weeks of treatment,especially in paresthesia,nervousness,and formication.The FSH and E_2 levels in both Kuntai and Tibolone groups were obviously decreased when compared with the pre-treatment(P<0.05),and these hormone levels in Kuntai group were comparable to those in Tibolone group.No adverse events occurred in either group. CONCLUSION: In the short-term treatment of GnRH-a,Kuntai capsule exhibits significant alleviating effects on perimenopause symptoms caused by GnRH-a with high safety and few adverse reactions.

A Phosphate-Starvation Induced RING-Type E3 Ligase Maintains Phosphate Homeostasis Partially Through OsSPX2 in Rice.

Phosphate (Pi), as the main form of phosphorus that can be absorbed by plants, is one of the most limiting macro-nutrients for plants. However, the mechanism for maintaining Pi homeostasis in rice (Oryza sativa) is still not well understood. We identified a Pi-starvation-induced E3 ligase (OsPIE1) in rice. Using an in vitro self-ubiquitination assay, we determined the E3 ligase activities of OsPIE1. Using GUS staining and GFP detection, we analyzed tissue expression patterns of OsPIE1 and the subcellular localization of its encoded protein. The function of OsPIE1 in Pi homeostasis was analyzed using OsPIE1 overexpressors and ospie1 mutants. OsPIE1 was localized to the nucleus, and expressed in epidermis, exodermis and sclerenchyma layers of primary root. Under Pi-sufficient condition, overexpression of OsPIE1 upregulated the expression of OsPT2, OsPT3, OsPT10 and OsPAP21b, resulting in Pi accumulation and acid phosphatases (APases) induction in roots. OsSPX2 was strongly suppressed in OsPIE1 overexpressors. Further comparative transcriptome analysis, tissue expression patterns and genetic interaction analysis indicated that the enhancing of Pi accumulation and APase activities upon overexpression of OsPIE1 was (at least in part) caused by repression of OsSPX2. These results indicate that OsPIE1 plays an important role in maintaining Pi homeostasis in rice.

Deregulation of microRNA expression in thyroid tumors.

MicroRNAs (miRNAs or miRs) are endogenous non-coding RNAs that negatively regulate gene expression by binding to the 3' non-coding regions of target mRNAs, resulting in their cleavage or blocking their translation. miRNAs may have an impact on cell differentiation, proliferation, and survival, and their deregulation can be inclined to diseases and cancers, including thyroid tumors. The purpose of this review is to summarize the existing findings of deregulated miRNAs in different types of thyroid tumors and to exhibit their potential target genes, especially to demonstrate those involved in tumor invasion and metastasis. In addition, new findings of circulating miRNA expression profiles, single nucleotide polymorphism (SNP) in thyroid tumors, and the correlation of somatic mutations with deregulated miRNA expression in thyroid tumors were all included in this review.

[Meta-analysis of laparoscopic Nissen and Toupet fundoplication for gastro-oesophageal reflux disease].

OBJECTIVE: To compare laparoscopic Nissen fundoplication (LNF)and Toupet laparoscopic fundoplication (LTF) with respect to treatment outcomes and postoperative complications. METHODS: PubMed, Medline, Embase and the Cochrane Library were searched. Only randomized controlled trials (RCTs) comparing laparoscopic Nissen and Toupet fundoplication were included. Outcomes evaluation included occurrences of heartburn, reflux, difficulty swallowing, chest pain, abdominal distention, failure to hiccup, diarrhea, and early complications and degree of patient satisfaction at early (three to six months) and later (one to three years) post-operative periods. RESULTS: Of 939 patients in seven RCTs, 478 received LNF and 461 received LTF. For both groups, control of reflux was good and occurrence of heartburn was similar (P>0.05). A lower incidence of postoperative dysphagia for both early and later post-operative periods, but a higher overall complication rate in early post-operative period were observed in the LTF group (P<0.05). Patient satisfaction was similar (P>0.05). CONCLUSIONS: LNF and LTF are both safe and effective. The adoption of procedure should be based on the patient status and surgeon experience.

Upregulated CD133 expression in tumorigenesis of colon cancer cells.

AIM: To analyze the upregulated CD133 expression in tumorigenesis of primary colon cancer cells. METHODS: Upregulated CD133 expression in tumorigenesis of colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) was analyzed by flow cytometry. Human colon cancer tissue samples were stained with anti-human CD133. SW620 cells were sorted according to the CD133 expression level measured by fluorescence-activated cell sorting. Spheroids of colorectal cancer cells were cultured with the hanging drop. Expression of CD133 and Lgr5 in spheroids of colorectal cancer cells and monolayer culture was detected by RT-qPCR. Spheroids of colorectal cancer cells were analyzed using anti-human CD133 with immunohistochemical staining. RESULTS: CD133 antigen was expressed in colorectal cancer cell lines (Lovo, Colo205, Caco-2, HCT116 and SW620) as well as in primary and metastatic human colon cancer tissues. However, the CD133 was differently expressed in these cell lines and tissues. The expression levels of CD133 and Lgr5 were significantly higher in spheroids of parental, CD133(hi) and CD133⁻ cells than in their monolayer culture at the mRNA level (P < 0.05). Immunohistochemical staining of spheroids of CD133⁻ cells showed that CD133 was highly expressed in colorectal cancer cell lines. CONCLUSION: Upregulated CD133 expression plays a role in tumorigenesis colorectal cancer cells, which may promote the expression of other critical genes that can drive tumorigenesis.

The expression changes of genes associated with protein metabolism, folding, transport, localizati on and assembly during rat liver regeneration.

To study the expression and function of protein metabolism, folding, transport, localization and assembly-associated genes in rat liver regeneration (LR) at transcriptional level, we obtained above genes from databases and scientific articles, detected their expression profiles in rat LR using Rat Genome 230 2.0 array, and determined liver regeneration-associated genes by comparing the partial hepatectomy (PH) group with sham operation (SO) group. Totally 1147 genes were preliminarily confirmed to be LR-associated. The results from the chip detection demonstrated that genes involved in the above biological processes were mostly up-regulated in rat LR; protein metabolism-participating genes were initially expressed mainly at 0.5-1 h and 16-30 h following PH; protein degradation-accelerating genes outnumbered protein accumulation-promoting genes between 0.5-12 h, whereas the latter were more than the former during 16-48 hours; protein synthesis-involved genes were more frequently up-regulated at 16,24,42 and 66 h, especially at 42 h; up-regulation of protein degradation-associated genes dominated almost during the whole period of LR, especially at forepart and prophase; the up-regulated protein folding-associated genes were predominant than down-regulated at 2, 16-24, 42, 66, 72 and 168 h, especially at 66 h; protein transport and localization-associated genes were predominantly up-regulated during the whole period of LR, especially at 66 h; and most of protein complex assembly-associated genes were up-regulated before 96 h, especially at 12 h. it was inferred according to the above analysis that protein synthesis was enhanced at metaphase of LR, and the activities of protein degradation, folding, transport, localization and assembly were vigorous almost during the whole period of LR.

Elevated expression of autocrine motility factor receptor correlates with overexpression of RhoC and indicates poor prognosis in hepatocellular carcinoma.

Our previous study identified RhoC as an invasion and metastasis marker in hepatocellular carcinoma patients. Recent document suggested RhoGTPase is required for autocrine motility factor signaling. In this study, we questioned whether there is a correlation between expression of autocrine motility factor receptor and RhoC. Furthermore, we questioned whether elevated expression of autocrine motility factor correlates with metastasis and poor prognosis of HCC. The mRNA expression level of AMFR and RhoC were examined by RT-PCR in 25 cases of HCC and pericarcinomatous liver tissues (PCLT). In addition, the correlation between the expression level of AMFR and clinical pathologic parameters was analyzed. Furthermore, follow-up information was collected to evaluate the prognostic value of AMFR for HCC patients. Our results showed that the expression of AMFR and RhoC significantly increased in HCC compared with PCLT; extrahepatic metastatic lesions expressed significantly higher levels of AMFR and RhoC than corresponding intrahepatic HCC tissues. There is a highly significant correlation of AMFR expression levels with tumor vein invasion, number of tumor nodes, and tumor stage. Anticipatively, positive correlation was observed between mRNA expression of AMFR and RhoC gene. Furthermore, the HCC patients with high-expression of AMFR had significant high recurrence/metastasis and shorter survival than those with low-expression of AMFR. Together, our findings suggested a strong correlation between the expression of AMFR and RhoC and also a correlation between overexpression of them and invasion and metastasis of HCC. Furthermore, our data indicated AMFR as a potential prognosis for HCC.

Expression patterns and action analysis of genes associated with hepatitis virus infection during rat liver regeneration.

AIM: To study the action of hepatitis virus infection-associated genes at transcription level during liver regeneration (LR). METHODS: Hepatitis virus infection-associated genes were obtained by collecting the data from databases and retrieving the correlated articles, and their expression changes in the regenerating rat liver were detected with the rat genome 230 2.0 array. RESULTS: Eighty-eight genes were found to be associated with liver regeneration. The number of genes initially and totally expressed during initial LR [0.5-4 h after partial hepatectomy (PH)], transition from G0 to G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and reorganization of structure-function (66-168 h after PH) was 37, 8, 48, 3 and 37, 26, 80, 57, respectively, indicating that the genes were mainly triggered at the early stage of LR (0.5-4 h after PH), and worked at different phases. These genes were classified into 5 types according to their expression similarity, namely 37 up-regulated, 9 predominantly up-regulated, 34 down-regulated, 6 predominantly down-regulated and 2 up/down-regulated genes. Their total up- and down-regulation frequencies were 359 and 149 during LR, indicating that the expression of most genes was enhanced, while the expression of a small number of genes was attenuated during LR. According to time relevance, they were classified into 12 groups (0.5 and 1 h, 2 and 4 h, 6 h, 8 and 12 h, 16 and 96 h, 18 and 24 h, 30 and 42 h, 36 and 48 h, 54 and 60 h, 66 and 72 h, 120 and 144 h, 168 h), demonstrating that the cellular physiological and biochemical activities during LR were fluctuated. According to expression changes of the genes, their expression patterns were classified into 23 types, suggesting that the cellular physiological and biochemical activities during LR were diverse and complicated. CONCLUSION: The anti-virus infection capacity of regenerating liver can be enhanced and 88 genes play an important role in LR.

[The polymorphism of Y chromosome and mtDNA distribution among two Bai populations].

In the same ethnic group, people residing at different places may have genetic difference. The difference can be the results of migration and admixture events happened in history. To clarify the genetic relationship and micro-evolution of two Bai ethnic populations residing in Yunnan and Hunan province respectively,we investigated their genetic difference from paternal and maternal genealogy with six other ethnic groups as outgroups. Fourteen loci from mtDNA and thirteen loci from Y chromosome were selected for genotyping using PCR-RFLP methods. Result showed that H6 and H8 are the same dominant Y chromosome haplotypes in two Bai groups. However,the distribution of mtDNA haplogroups showed difference between two Bai populations. D, B, M8 are the predominant haplogroups in Hunan Bai ethnic population, whereas M, G, F are dominant in Yunnan Bai ethnic population. Principal Component (PC) analysis based on the Y chromosome haplotypes showed that two Bai ethic populations cluster together. It shows a close paternal genetic relationship between two Bai ethnic populations. From the mtDNA PC plot, it is clear that Hunan Bai is close to Hunan Han and Tujia, whereas Yunnan Bai is close to ethnic groups living in Yunnan province. The difference of mtDNA haplogroup distribution in two Bai people may reflect the maternal gene flow between ethnic groups living in Hunan province after the ancestors of Hunan Bai migrated from Yunnan province to Hunan province 800 years ago.

[Genetic polymorphism of mitochondrial DNA in coding region in 16 ethnic populations of Yunnan].

The genetic polymorphism of mitochondrial DNA in the coding region in 16 ethnic populations of Yunnan was analyzed using PCR-RFLP in a total of 654 samples. Seventeen haplogroups were found, four of which were undefined haplogroups. Haplogroup distribution and Principal Component (PC) analysis showed that the ethnic groups descended from Bai-Yue tribe have B, F and M7 as the predominant haplogroups,which indicated their origination from southern China. Haplogroup A, D and N9 were predominant in the Mongolian ethnic group, reflecting their north-originated characteristics. The groups descended from Di-Qiang tribe shared the predominant haplogroups with both the south and north originated groups,which demonstrated that they inherit the maternal characteristics from both southern and northern populations. There is genetic difference among the populations in the same ethnic group and is usually smaller than that among the ethnic groups from different ancient tribes, but not necessarily smaller than that among the groups from the same tribe.

[Principal component analysis of Y-chromosome haplotype distribution in 18 ethnic groups in Yunnan Province].

Based on the historical records, 18 of the 26 ethnic groups in Yunnan Province are the descendant populations of three ancient tribes, Bai-Yue, Bai-Pu and Di-Qiang, linguistically belonging to the Daic, Austro-Asiatic and Tibeto-Burman, respectively. In order to trace the origins of these native ethnic groups, a total of 13 East Asian specific Y-chromosome biallelic markers were used to study the genetic structure of 20 local populations covering all the 18 ethnic groups in Yunnan Province. Haplotypes were analysis by PCR-RFLP method. Our results showed that H11 and H12 were the predominant haplotypes in the descendant populations of Bai-Yue tribe. H5, H6 and H8 were the dominant haplotypes in Di-Qiang descendants, and the frequencies of H6, H8 and H11 were very high in the descendant populations of Bai-Pu. To investigate relationships among 20 populations, a three dimensional PC analysis were performed based on the distribution of the 13 haplotypes. All populations were divided into two clusters in the PC plot. The first cluster was mainly composed by the descendant populations of Bai-Yue, and the second one was mainly composed by the descendants of Di-Qiang tribe. This result indicated that Bai-Yue and Di-Qiang's paternal lineage had different origins, which was in agreement with the historical documents and linguistic classification.

[Overexpression of the RhoC gene correlates with invasion and metastasis of hepatocellular carcinoma].

OBJECTIVE: Rho, a ras homologous gene, encodes a group of GTP-binding proteins. Our previous study suggested that one member of the Rho gene family, RhoC, was related to the progression of human hepatocellular carcinoma (HCC). This study is to elucidate correlation of Rho overexpression with invasion and metastasis of HCC. METHODS: The expression level of RhoC mRNA and protein in 25 cases of HCC and adjacent non-cancerous liver tissue was examined by RT-PCR and Western blot. Mutation of RhoC gene was examined by PCR-SSCP. RESULTS: The expression of RhoC mRNA and protein was found in all HCC and adjacent non-cancerous liver tissue. The expression level of RhoC mRNA and protein was significantly higher in tumor tissue than in adjacent non-cancerous liver tissue (1.8 +/- 1.1 vs 1.0 +/- 0.7; 33 992 +/- 10 384 vs 17 342 +/- 9998, P < 0.01). The degree of RhoC overexpression was even more marked in metastatic lesions than in primary tumors (P < 0.01). Overexpression of the rhoC gene was significantly correlated with such clinic-pathological findings as cell differentiation, portal vein invasion, number of primary tumor nodules and metastatic lesions (P < 0.05). Mutation of RhoC gene was found in none of the HCC specimens examined. CONCLUSION: Overexpression of RhoC gene may play an important role in carcinogenesis and progression of HCC.

Expression and significance of RhoC gene in hepatocellular carcinoma.

AIM: To investigate the expression of RhoC gene in hepatocellular carcinoma (HCC) and to evaluate the relationship between RhoC gene expression and invasion and metastasis of HCC. METHODS: mRNA expression level of RhoC gene was examined by reverse transcription-polymerase chain reaction (RT-PCR) in 25 cases of HCC and para-cancerous normal liver tissues. In addition, mutation of RhoC gene was examined by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). RESULTS: The mRNA expression levels of RhoC in tumor tissues were significantly higher than those in para-cancerous normal liver tissues (1.8+/-1.1 vs 1.0+/-0.7, P<0.01). The metastatic lesions outside of liver also showed significantly higher RhoC mRNA levels than corresponding tumor tissues in liver (3.3+/-0.5 vs 2.0+/-0.7, P<0.01). There were significant associations between RhoC gene expression and certain clinical and pathological findings, including cell differentiation, vein invasion, number of tumor nodes and metastatic lesions. Mutation of RhoC gene was not found by PCR-SSCP. CONCLUSION: The RhoC gene may be related to malignant transformation and development of HCC and may play an important role in the invasion and metastasis of HCC by overexpression but not mutation.

[The frequency distribution of flavin-containing monooxygenase 3 mutant alleles in 28 populations from Yunnan].

OBJECTIVE: To study the frequency distribution of flavin-containing monooxygenase 3 (FMO3) mutant alleles in 28 populations originating from 24 ethnic minorities in Yunnan of China. METHODS: FMO3 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The average frequencies of FMO3/Stop(148), FMO3/Lys(158) and FMO3/Gly(308) were 0.395(0.174-0.803), 0.208 (0.056-0.414), 0.046(0-0.217), respectively. The frequencies of FMO3/Gly(308) in Blang, Huayaodai, Shuidai, Zhuang, De'ang, Jingpo, Nu and Hui populations were null. CONCLUSION: It was found that the frequencies of FMO3 mutant alleles varied not only in different ethnic groups, but also in different populations that stemmed from the same ethnic group.

Tri-iodothyronine supplement protects gut barrier in septic rats.

AIM: To investigate the role of tri-iodothyronine supplement in protecting gut barrier in septic rats. METHODS: Twenty-two rats were randomized into three groups: sham group (n=6), sepsis group (n=8), and sepsis plus tri-iodothyronine (T(3)) group (n=8). Septic rat model was established through cecal ligation and puncture (CLP). After 5 h, sham and sepsis groups received saline, and the remaining group received T(3) intraperitoneally. Twenty-one hrs After CLP, intestinal permeability and serum free T(3) and T(4) were measured with fluorescence spectrophotometer and by radioimmunoassay, respectively. Intestinal ultrastructure and histologic morphology were observed under transmission electron microscopy (TEM) and light microscopy, respectively. RESULTS: After 21 h, septic symptoms and signs in sepsis plus T(3) group were milder than those in sepsis group. Serum FT(3) or FT(4) concentration in sepsis group was lower than that in sham group (1.59+/-0.20, 3.41+/-2.14 pmol/L vs 3.44+/-1.40, 9.53+/-3.39 pmol/L, P<0.05), and FT(3) concentration in sepsis plus T(3) group (3.40+/-1.65 pmol/L, P<0.05) was corrected. Portal concentration of fluorescein isothiocyanate-dextran (FITC-D) in sepsis group (2.51+/-0.56 mg/L) was higher than that in sham group (1.22+/-0.21 mg/L) (P<0.01), and in sepsis plus T(3) group (1.68+/-0.38 mg/L) it was decreased significantly(P<0.01). TEM and light microscopy showed that T(3) supplement preserved well ultrastructure and morphology of intestinal mucosa in septic rats. CONCLUSION: Tri-iodothyronine supplement protects gut barrier in septic rats.