HBV DNA Integration into Telomerase or MLL4 Genes and TERT Promoter Point Mutation as Three Independent Signatures in Subgrouping HBV-Related HCC with Distinct Features.

Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform. Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC. Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort. Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.

On the Time Value of Yu Weihan’s Spiritual Strength / 中国医学伦理学

Yu Weihan, academician of the Chinese Academy of Engineering, devoted his whole life to the prevention and control of endemic diseases and basically eradicated the epidemic of Keshan disease. Academician Yu Weihan’s struggle experience has left us with valuable spiritual wealth. His spiritual strength is manifested in many aspects, such as the spirit of bearing hardships first, the spirit of innovative daring to be the first, the spirit of craftsmen striving for perfection, the patriotic spirit of caring for the people, and the dedication of being indifferent to fame and wealth. His great medical feelings of bravely shouldering the mission, caring for the people and taking root in the grass-roots have forcefully answered the three important questions: what kind of doctor to be, who to be and how to be a good doctor in the learning and working career of doctors in the new era. He set an model for doctors in later generations and highlighted the value of this spiritual strength for the time.

Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC.

Hepatitis B virus (HBV) DNA integration is an incidental event in the virus replication cycle and occurs in less than 1% of infected hepatocytes during viral infection. However, HBV DNA is present in the genome of approximately 90% of HBV-related HCCs and is the most common somatic mutation. Whole genome sequencing of liver tissues from chronic hepatitis B patients showed integration occurring at random positions in human chromosomes; however, in the genomes of HBV-related HCC patients, there are integration hotspots. Both the enrichment of the HBV-integration proportion in HCC and the emergence of integration hotspots suggested a strong positive selection of HBV-integrated hepatocytes to progress to HCC. The activation of HBV integration hotspot genes, such as telomerase (TERT) or histone methyltransferase (MLL4/KMT2B), resembles insertional mutagenesis by oncogenic animal retroviruses. These candidate oncogenic genes might shed new light on HBV-related HCC biology and become targets for new cancer therapies. Finally, the HBV integrations in individual HCC contain unique sequences at the junctions, such as virus-host chimera DNA (vh-DNA) presumably being a signature molecule for individual HCC. HBV integration may thus provide a new cell-free tumor DNA biomarker to monitor residual HCC after curative therapies or to track the development of de novo HCC.

A preliminary study on reducing the formation of intra-abdominal hernia and postoperative intestinal obstruction in laparoscopic Bricker operation / 现代泌尿外科杂志

【Objective】 To reduce the incidence of postoperative intestinal obstruction, we tried to improve surgical techniques by closing the cavity formed during radical cystectomy + ileal passage (Bricker) via laparoscopy to prevent the formation of abdominal hernia. 【Methods】 During Oct.2018 and Feb.2022, 41 patients were involved (conventional group). After standard laparoscopic radical cystectomy + pelvic lymphadenectomy, the ileum channel was established. The right medial retroperitoneum was sutured to cover the mesothelium and end of the ileum channel under open operation or endoscope. The space between the ureter and mesothelium of the ileum channel was sealed, and the end of the ileum channel and both ureters were externalized. During Feb.2022 and Dec.2022, 15 patients were involved (modified group). The right inner and outer lateral peritoneums below the ileal conduit were sutured to "bottom out" the gap between the ileal conduit and the right abdominal wall in addition to standard procedures. The recovery of intestinal function and incidence of bowel obstruction were compared between the two groups. 【Results】 In the conventional group, the intestinal function recovered within 2 to 6 days after surgery, with a median ventilation time of 3 days. Intestinal obstruction occurred in 3 patients, 2 of whom improved after conservative treatment while 1 underwent surgical exploration after ineffective conservative therapy. There were no significant differences in the time of discharge and ventilation between the two groups, but no intestinal obstruction occurred in the modified group. 【Conclusion】 Peritoneal externalization at the end of ileal passage can reduce the incidence of intra-abdominal hernia and postoperative intestinal obstruction, which is worthy of clinical application.

Discussion on the technical points of laparoscopic anterior approach to right hemihepatectomy / 中华肝胆外科杂志

Unlike the traditional surgical approach, which requires priority treatment of the perihepatic ligament and rotation of the liver, the anterior approach to the right hemicolectomy does not deal with the perihepatic ligament prior to parenchymal dissection and rotate and move the liver. The advantage is that it is more in line with the tumor-free principle and reduces unnecessary free. The disadvantage is that it is relatively difficult to control bleeding during the cleavage of the liver and there is some risk in the handling of the lower part of the vena cava sulcus. However, with the popularization and application of laparoscopy, it is more suitable for performing anterior approach right hemicolectomy than open surgery due to its unique caudodorsal view advantage, finer local anatomical structure display and subtle manipulation. This article discusses the procedures and technical points of laparoscopic right hemihepatectomy through the anterior approach.

Effect of Modified Chaihu Shugansan on Gallbladder Function and Inflammatory Cytokines Levels in Treatment of Chronic Cholecystitis Cholelithiasis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and influence of modified Chaihu Shugansan combined with ursodeoxycholic acid tablets on inflammatory factors in treatment of chronic cholecystitis cholelithiasis （stagnation of liver and gallbladder Qi）. Method:One hundred and ten patients were randomly divided into control group （60 cases） and observation group （60 cases）. Both groups received lifestyle intervention， and oral ursodeoxycholic acid tablets， 50 mg/time， taken in the morning and evening meals. Patients in control group additionally took Yidanshu capsules orally， 4 capsules/time， 3 times/day. Patients in observation group additionally took modified Chaihu Shugansan orally， 1 dose/day. The treatment courses continued 3 months in both groups. Before and after treatment， traditional Chinese medicine （TCM） symptom scores were graded， the ultrasound status of chronic gallbladder inflammation， gallbladder contraction function and stones was graded， the levels of interleukin-6 （IL-6）， IL-8， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and nuclear transcription factor-<italic>κ</italic>B（NF-<italic>κ</italic>B）Were detected， and safety was evaluated. The efficacy for TCM syndromes， imaging efficacy and the efficacy for eliminating gallbladder stones were compared between the two groups. Result:The efficacy for TCM syndrome， efficacy on color ultrasound for chronic cholecystitis and the efficacy on imaging for cholelithiasis in the observation group were all better than those in the control group（<italic>Z</italic>=2.104<italic>，Z</italic>=2.076，<italic>Z</italic>=2.101，<italic>P</italic><0.05）. The thickness of gallbladder wall and volume of the gallbladder of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， and gallbladder contraction function was higher than that in control group （<italic>P</italic><0.01）. Levels of IL-6， IL-8， TNF-<italic>α</italic> and NF-<italic>κ</italic>B in observation group were lower than those in control group （<italic>P</italic><0.01）. Conclusion:modified Chaihu Shugansan combined with ursodeoxycholic acid in the treatment of chronic cholecystitis and cholelithiasis （liver and gall Qi stagnation） is better than Yidanshu capsule combined with ursodeoxycholic acid sour scheme in terms of clinical efficacy， imaging efficacy， and elimination of gallbladder stones. It can reduce inflammation， and enhance gallbladder contraction， with high safety in clinical use.

Effectiveness and safety of two-step percutaneous transhepatic choledochoscopic lithotomy in treatment of complex hepatolithiasis / 临床肝胆病杂志

Objective To investigate the clinical effect of two-step percutaneous transhepatic choledochoscopic lithotomy (PTCSL) in the treatment of complex hepatolithiasis. Methods A retrospective analysis was performed for the clinical data of 118 patients with complex hepatolithiasis who were admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from January 2018 to June 2020, and according to the surgical procedure, they were divided into PTCSL group with 60 patients and surgery group with 58 patients. All patients were followed up for half a year to 3 years via telephone and outpatient service. The two groups were compared in terms of general information, perioperative indicators (including time of operation, intraoperative blood loss, incision length, time to first flatus and time to first defecation after surgery, time to extraction of abdominal drainage tube, and length of hospital stay), changes in liver function and inflammatory indicators, postoperative complications (bile leakage, acute cholangitis, wound infection, and venous thrombosis of lower extremities), stone clearance rate and recurrence rate, and quality of life. The two-independent-samples t -test was used for comparison of continuous data between two groups; the paired t -test was used for comparison between different periods of time within group; the chi-square test was used for comparison of categorical data between two groups. Results Compared with the surgery group, the PTCSL group had significantly shorter time of operation, time to first flatus and time to first defecation after surgery, and time to extraction of abdominal drainage tube, a significantly lower intraoperative blood loss, and a significantly shorter incision length (all P < 0.05). On day 1 after surgery, both groups had significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ( P < 0.05) and a significant increase in white blood cell count (WBC) ( P < 0.05), and the PTCSL group had significantly lower levels of ALT, AST, and WBC than the surgery group (all P < 0.05). Compared with the surgery group, the PTCSL group had significantly lower incidence rates of postoperative bile leakage (5.0% vs 17.2%, P < 0.05), acute cholangitis (3.3% vs 13.8%, P < 0.05), wound infection (1.7% vs 10.3%, P < 0.05), and venous thrombosis of lower extremities (1.7% vs 12.1%, P < 0.05). Compared with the surgery group, the PTCSL group had a significantly higher stone clearance rate (58.3% vs 37.9%, P < 0.05) and a significantly lower long-term stone recurrence rate (10.0% vs 20.7%, P < 0.05). The PTCSL group had significantly higher quality of life scores than the surgery group (all P < 0.05). Conclusion For the treatment of complex hepatolithiasis, two-step PTCSL can effectively remove stones, with the advantages of fast postoperative recovery, low recurrence rate and incidence rate of complications, and high quality of life, and therefore, it is an effective alternative surgical procedure.

A preliminary study on percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy in treatment of refractory liver abscess / 临床肝胆病杂志

Objective To investigate the clinical effect of percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy for necrosectomy and drainage in the treatment of refractory liver abscess after transcatheter arterial embolization (TACE). Methods A retrospective analysis was performed for three patients with refractory liver abscess after TACE in The Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine from January 2018 to December 2020, and among the three patients, one had the formation of liver abscess after TACE for hepatic metastases after pancreaticoduodenectomy, one had liver abscess after repeated TACE for massive hepatocellular carcinoma, and one had secondary liver abscess after TACE for traumatic hepatic rupture. All three patients received percutaneous transhepatic drainage and sequential percutaneous nephroscopy for the treatment of refractory liver abscess, and their specific treatment process was summarized. Results All three patients were diagnosed with refractory liver abscess based on CT, routine blood test, procalcitonin, blood culture, and clinical manifestation. Percutaneous transhepatic catheterization under the guidance of conventional ultrasonography or CT and effective antibiotics had an unsatisfactory therapeutic effect, and after sequential percutaneous nephroscopy was performed for necrosectomy and drainage, liver abscess was cured and the patients had good prognosis. Conclusion For refractory liver abscess after TACE, when routine puncture treatment has an unsatisfactory therapeutic effect or a patient cannot tolerate surgical operation, percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy is safe and effective in the treatment of refractory liver abscess.

Cell-Free Virus-Host Chimera DNA From Hepatitis B Virus Integration Sites as a Circulating Biomarker of Hepatocellular Cancer.

BACKGROUND AND AIMS: Early recurrence of hepatocellular carcinoma (HCC) after surgical resection compromises patient survival. Timely detection of HCC recurrence and its clonality is required to implement salvage therapies appropriately. This study examined the feasibility of virus-host chimera DNA (vh-DNA), generated from junctions of hepatitis B virus (HBV) integration in the HCC chromosome, as a circulating biomarker for this clinical setting. APPROACH AND RESULTS: HBV integration in 50 patients with HBV-related HCC was determined by the Hybridization capture-based next-generation sequencing (NGS) platform. For individual HCC, the vh-DNA was quantified by specific droplet digital PCR (ddPCR) assay in plasma samples collected before and 2 months after surgery. HBV integrations were identified in 44 out of 50 patients with HBV-related HCC. Tumor-specific ddPCR was developed to measure the corresponding vh-DNA copy number in baseline plasma from each patient immediately before surgery. vh-DNA was detected in 43 patients (97.7%), and the levels correlated with the tumor sizes (detection limit at 1.5 cm). Among the plasma collected at 2 months after surgery, 10 cases (23.3%) still contained the same signature vh-DNA detected at baseline, indicating the presence of residual tumor cells. Nine of them (90%) experienced HCC recurrence within 1 year, supporting vh-DNA as an independent risk factor in predicting early recurrence. Analysis of circulating vh-DNA at recurrence further helped identify the clonal origin. A total of 81.8% of recurrences came from original HCC clones sharing the same plasma vh-DNA, whereas 18.2% were from de novo HCC. CONCLUSIONS: vh-DNA was shown to be a circulating biomarker for detecting the tumor load in majority of patients with HBV-related HCC and aided in monitoring residual tumor and recurrence clonality after tumor resection.

The complete mitochondrial genome of Meretrix lusoria (Bivalvia: Veneroida: Veneridae) from Kumamoto, Japan.

We sequenced and assembled the complete mitochondrial genome sequence of the Meretrix lusoria, from Kumamoto, Japan. The length of mitogenome is 20,180 bp, including 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. The nucleotide composition of the mitogenome was 25.73% for A, 42.41% for T, 9.35% for C, and 22.49% for G. The AT and GC skewness of mitogenome sequence are -0.245 and 0.412, showing the T-skew and G-skew. The reconstructed phylogenetic relationships of 25 Bivalvia species based on 12 protein-coding genes were highly supported and the clade of all Meretrix clams included had a support value of 99%. Our results shall provide a better understanding in the evolutionary histories of the Veneroida and relative species.

Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth.

Neutrophil infiltration and neutrophil extracellular traps (NET) in solid cancers are associated with poorer prognosis, but the mechanisms are incompletely understood. We hypothesized that NETs enhance mitochondrial function in tumor cells, providing extra energy for accelerated growth. Metastatic colorectal cancer tissue showed increased intratumoral NETs and supranormal preoperative serum MPO-DNA, a NET marker. Higher MPO-DNA correlated with shorter survival. In mice, subcutaneous tumor implants and hepatic metastases grew slowly in PAD4-KO mice, genetically incapable of NETosis. In parallel experiments, human cancer cell lines grew slower in nu/nu mice treated with DNAse, which disassembles NETs. PAD4-KO tumors manifested decreased proliferation, increased apoptosis, and increased evidence of oxidative stress. PAD4-KO tumors had decreased mitochondrial density, mitochondrial DNA, a lesser degree of ATP production, along with significantly decreased mitochondrial biogenesis proteins PGC1α, TFAM, and NRF-1. In vitro, cancer cells treated with NETs upregulated mitochondrial biogenesis-associated genes, increased mitochondrial density, increased ATP production, enhanced the percentage of cancer cells with reduced mitochondrial membrane potential, and increased the oxygen consumption rate. Furthermore, NETs increased cancer cells' expression of fission and fusion-associated proteins, DRP-1 and MFN-2, and mitophagy-linked proteins, PINK1 and Parkin. All of which were decreased in PAD4-KO tumors. Mechanistically, neutrophil elastase released from NETs activated TLR4 on cancer cells, leading to PGC1α upregulation, increased mitochondrial biogenesis, and accelerated growth. Taken together, NETs can directly alter the metabolic programming of cancer cells to increase tumor growth. NETs represent a promising therapeutic target to halt cancer progression. SIGNIFICANCE: Neutrophils through the release of NETs facilitate the growth of stressed cancer cells by altering their bioenergetics, the inhibition of which induces cell death.

Research progress of distal pancreatectomy with en bloc celiac axis resection / 中华消化外科杂志

Carcinoma of pancreatic body and tail is a high invasive disease with a low resectability rate.It was once believed that celiac axis infiltration usually contraindicated resection.Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is described as a new treatment method of this disease.In recent years,more and more literatures have reported this operation,but they were case reports or small sample retrospective study,the results of which differed according to the different treatments and perioperative managements in different centers.The advantages and disadvantages of DP-CAR are still controversial.Research progress of DP-CAR is reviewed in this article.

Application of three-dimensional visualization technology in robotic nephron-sparing surgery / 中华泌尿外科杂志

Objective To explore the potential value of applying three-dimensional visualization technology in the robot-assisted laparoscopic nephron sparing partial nephrectomy.Methods From January to December 2018,98 patients with renal carcinoma undergoing robot-assisted laparoscopic nephron sparing surgery were retrospectively analyzed.Forty-one patients in the experimental group accomplished kidney CT examination and three-dimensional reconstruction before surgery,and fifty-seven patients in the control group only completed kidney CT examination.There were 20 males and 21 females in the experimental group with the age of (51.39 ± 14.80) years and body mass index (BMI) of (23.54 ± 3.08) kg/m2.The median tumor diameter was 3.40 cm (range 1.90-8.30 cm) and the mean R.E.N.A.L.score was (5.83 ± 1.51) in the experimental group including 11 cases of transperitoneal,17 cases of retroperitoneal and 13 cases of combined transperitoneal and retroperitoneal access.There were 35 males and 22 females in the control group with the age of (52.84 ± 12.28) years and BMI of (24.01 ±3.30)kg/m2.The median tumor diameter was 3.35 cm (range 1.40-7.0 cm) and the mean R.E.N.A.L.score was (6.17 ± 1.77) in the control group including 15 cases of transperitoneal,31 cases of retroperitoneal and 11 cases of combined transperitoneal and retroperitoneal access.There was no statistical difference between two groups in term of age,gender,BMI score,R.E.N.A.L.score,tumor size,tumor location and operative approach.Results Ninety-eight cases of operation were successfully completed without causing vascular and ureteral injury.The warm ischemia time in the experimental group was significantly shorter than that of the control group [median 15.0 (7.0-26.0) min vs.20.0 (10.0-28.0) min,P--0.02],while no statistical difference was observed in term of operation time [median 130.0 (65.0-340.0) min vs.139.0 (67.0-250.0) min,P =0.22].There was no significant difference between the two groups in the decrease of hemoglobin within 24 hours after operation [median 20.0 (4.0-39.0) g/L vs.15.5 (2.0-40.0) g/L,P =0.56] and the average length of hospital stay after operation [median 6.0(4.0-14.0) d vs.6.0(5.0-14.0) d,P =0.86].The trend of creatinine declining was not statistically significant between the two groups at both 24 hours [median:2.0 (-10.0-28.0) μmol/L vs.7.5 (-17.0-51.0) μ mol/L,P =0.24] and 6 months after operation [median:2.0 (-12.0-57.0) μ mol/L vs.4.5 (-3.0-24.0) μmol/L,P =0.39].Conclusions Preoperative three-dimensional reconstruction is helpful to shorten the warm ischemia time,but it did not show short-term and long-term protection for renal function.

Research progress of pancreatic enzyme replacement therapy after gastric resection / 国际外科学杂志

Gastric resection can cause a multifactorial clinical manifestations of dyspepsia,such as flatulence,diarrhea,weight loss,and fat diarrhea.Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat maldigestion following gastric surgery,the main causes may be related to rapid gastric emptying;asynchrony between gastric emptying and bilio-pancreatic secretion due to new tracts of various reconstructions;bacterial overgrowth after gastrectomy and so on.Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for EPI,due to lack of available evidence so far,the efficacy and safety of pancreatic enzyme substitution in patients following gastric resection remains unclear and cannot be generally recommended.This review will sum up the revelant studies addressing EPI and PERT after gastric resection in recent years,and summarizes the mechanisms,clinical diagnostic methods and PERT treatment perscription of EPI after gastrectomy to improve the cognition of clinicans.

The complete mitochondrial genome of Montipora aequituberculata (Scleractinia, Acroporidae).

The complete mitogenome of the hexacorallia, Montipora aequituberculata has been amplified and sequenced. The mitogenome consists of 17,886 bp, with 13 protein-coding genes, 2 ribosomal RNA genes, 2 transfer RNA genes and a control region. It has been observed that ND5 gene is split into two parts by a large fragment of genes, which commonly presented in scleractinian coral. The overall base composition of the H-strand was A, 24.91%; G, 24.1%; C, 14.2%; and T, 36.8%, with a slight AT bias of 61.7%. The control region was 627 bp in length and located between 12S rRNA and COIII gene. Based on the neighbour-joining (NJ) tree, M. aequituberculata was grouped with M. cactus, Anacropora matthai and Acropora tenuis, and formed a clade of Acroporidae. In conclusion, the complete mitogenome of M. aequituberculata data may provide more informative for phylogenetic approach for corals phylogeny.

Complete mitochondrial genome of the palemargin grouper Epinephelus bontoides (Pisces: Perciformes).

The complete mitogenome of the palemargin grouper, Epinephelus bontoides, was presented in this study. This mitochondrial genome consists of 16 903 bp, follow the typical gene arrangement with 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region (CR). The overall base composition was A, 28.7%; G, 16.1%; C, 28.0%; and T, 27.2%. The control region was 1200 bp in length, which located between tRNAPro and tRNAPhe, rich in A + T (69.2%) content. Based on the Neighbor-Joining (NJ) tree, E. bontoides was grouped with E. trimaculatus, E. quoyanus, E. areolatus, and E. bleekeri, and then combined with E. merra formed a clade. This complete mitogenome of E. bontoides can provide essential phylogenetic information of Epinephelus.

Relationship Between Blood Pressure Rhythm and Cognitive Function in Elderly Hypertension Patients / 中国循环杂志

Objective: To study the relationship between blood pressure (BP) rhythm and cognitive function in elder hypertension patients. Methods: Our research included in 2 groups: Hypertension group:n=74 patients≥80 years and Control group, n=36 elder subjects without hypertension. 24-hour ambulatory blood pressure monitoring (ABPM) was conducted in both groups. According to nocturnal BP reduction rate, Hypertension group was further divided into 4 subgroups as Dipper type BP subgroup, Non-dipper type BP subgroup, Anti-dipper type BP subgroup and Super-dipper type BP subgroup. Cognition function was evaluated by Mini-menta state examination (MMSE) form, MMSE score was compared among different groups and subgroups. Results: By MMSE score, the abilities of orientation, memory, attention, calculation and recall were different between Hypertension group and Control group,P<0.05. By MMSE score, the abilities of orientation and memory were different between Anti-dipper type BP subgroup and Dipper type BP subgroup,P<0.05; the abilities of orientation, memory, attention, calculation and recall were different between Non-dipper type BP subgroup and Dipper type BP subgroup,P<0.05; the memory was different between Super-dipper type BP subgroup and Dipper type BP subgroup,P<0.05. Conclusion: In elderly hypertension patients, compared to those with normal BP rhythm, the abnormal BP rhythm patients had the higher probability to suffer from cognitive dysfunction which was mainly as decreased abilities of orientation, memory, attention, calculation and recall.

Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4.

Glucosaminyl N-deacetylase/N-sulfotransferases (NDSTs) are the first enzymes that mediate the initiation of heparan sulfate sulfation. We previously identified NDST4 as a putative tumor suppressor in human colorectal cancer. In the study, we generated an Ndst4 knockout (Ndst4-/-) mouse strain and explored its phenotypic characteristics, particularly in the development of colonic epithelial homeostasis. The Ndst4-deficient mice were viable and fertile, and their life spans were similar to those of wild-type littermates. No gross behavioral or morphological differences were observed between the Ndst4-/- and wild-type mice, and no significant changes were determined in the hematological or serum biochemical parameters of the Ndst4-/- mice. Ndst4 RNA transcripts were expressed in the brain, lung, gastrointestinal tract, pancreas, and ovary. However, Ndst4-null mice exhibited no gross or histological abnormalities in the studied organs, except for the colon. Although no alterations were observed in the crypt length or number of proliferating cells, the Ndst4-/- mice exhibited an increased number of goblet cells and a decreased number of colonocytes in the proximal colon compared with the wild-type mice. Moreover, Ndst4 deficiency increased the basal level of apoptosis in the colonic epithelium. Taken together, we established, for the first time, an Ndst4-/- mouse strain and revealed the involvement of Ndst4 in the development and homeostasis of colonic epithelium. Accordingly, NDST4 in human colon might direct the biosynthesis of specific heparan sulfate proteoglycans that are essential for the maintenance of colonic epithelial homeostasis. Thus, the loss of its function may result in the tumorigenesis and progression of colorectal cancer.

DNA barcoding reveals that the common cupped oyster in Taiwan is the Portuguese oyster Crassostrea angulata (Ostreoida; Ostreidae), not C. gigas.

The Pacific cupped oyster, Crassostrea gigas, is one of the major aquacultural shellfish species that has been introduced to Europe and America from its native source in the West Pacific. In Taiwan, the cultivated cupped oysters along the west coast have been identified as C. gigas for over centuries; however, several molecular phylogenetic studies have cast doubt upon the existence of this species in Taiwan and adjacent waters. Indeed, our analyses of mitochondrial cytochrome oxidase I (COI) sequences from 313 Crassostrea collected from 12 locations along Taiwanese and southern Chinese coastlines confirm that all samples were the Portuguese oyster, C. angulata, rather than C. gigas. Multiple lines of evidence, including haplotypic and nucleotide diversity of the COI gene, demographic history, and population genetics, suggest that Taiwanese C. angulata is unique, probably experienced a sudden population expansion after the Last Glacial Maxima around 20,000 years ago, and has a significantly limited genetic connectivity across the Taiwan Strait. Our study applies an extended sampling and DNA barcoding to confirm the absence of C. gigas in natural and cultivated populations in Taiwan and southern China, where we only found C. angulata. We highlight the importance of conserving the gene pool of the C. angulata population in Taiwan, particularly considering the current threats by large-scale environmental disturbances such as marine pollution, habitat destruction, and climate change.