[Use of indocyanine green fluorescence navigation in laparoscopic anatomical hepatectomy].

Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ2 test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.

[Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: a case-control and Mendelian randomization study].

OBJECTIVE: To explore the causal association between circulating leptin levels and the risk of colorectal adenoma and colorectal cancer. METHODS: We collected demographic and clinical data and serum samples from 497 patients with colorectal adenoma, 955 patients with colorectal cancer, and 911 healthy individuals from the First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Cancer Hospital, Zhuji People's Hospital, and Lin'an District First People's Hospital. Instrumental variables of leptin were selected and genotyping tests were performed. A logistic regression model and stratified analysis were used to evaluate the association of serum leptin levels with colorectal adenoma, colorectal cancer, and the progression of colorectal adenoma to colorectal cancer. Genetic risk score (GRS) and single nucleotide polymorphisms (SNPs) were further used as instrumental variables in one-sample and two-sample Mendelian randomization analyses leveraging two-stage least squares and inverse-variance weighted methods to estimate the causal association of leptin levels with the risk of colorectal adenoma, colorectal cancer, and progression of colorectal adenoma to colorectal cancer. RESULTS: High levels of leptin, compared with its lowest quartile, were positively correlated with colorectal adenoma (P=0.005) and negatively with colorectal cancer (P < 0.001) and the risk of progression of colorectal adenoma to colorectal cancer (P < 0.001). Mendelian randomization analysis showed that GRS of leptin, either weighted or not, was not significantly correlated with the risk of colorectal adenoma, colorectal cancer, or the progression of colorectal adenoma to colorectal cancer, nor did the two-sample Mendelian randomization study support an association between leptin and the risk of colorectal cancer (P>0.05). CONCLUSION: Although the case-control study suggests probable correlations of leptin with the risk of colorectal adenoma, colorectal cancer, and colorectal adenoma progression to colorectal cancer, Mendelian randomization studies did not support a causal association of leptin with the risks of colorectal adenoma, colorectal cancer, or colorectal adenoma progression to colorectal cancer.

Genetic parameters and weighted single-step genome-wide association study for supernumerary teats in Holstein cattle.

Supernumerary teats (SNT) are a common epidermal abnormality of udders in mammals. The SNT negatively affect machine milking ability, udder health, and animal welfare and sometimes act as reservoirs for undesirable bacteria, resulting in economic losses on calves and lactating cows due to the cost of SNT removal surgery, early culling, and low milk yield. This study aimed to analyze the incidence and genetic parameter of SNT and detect SNT-related genes in Chinese Holstein cattle. In this study, the incidence of SNT was recorded in 4,670 Chinese Holstein cattle (born between 2008 and 2017) from 2 farms, including 734 genotyped cows with 114,485 SNPs. The SNT had a total frequency of 9.8% and estimated heritability of 0.22 (SE = 0.07), which were obtained using a threshold model in the studied Chinese Holstein population. Furthermore, we calculated approximate genetic correlations between SNT and the following indicator traits: 12 milk production, 28 body conformation, 5 fertility and reproduction, 5 health, and 9 longevity. Generally, the estimated correlations, such as 305-d milk yield for third parity (-0.55; SE = 0.02) and age at first calving in heifer (0.19; SE = 0.03), were low to moderate. A single-step GWAS was implemented, and 10 genes associated with SNT located in BTA4 were identified. The region (112.70-112.90 Mb) on BTA4 showed the highest genetic variance for SNT. The quantitative trait loci on BTA4 was mapped into the RARRES2 gene, which was previously shown to affect adipogenesis and hormone secretion. The WIF1 gene, which was located in BTA5, was also considered as a candidate gene for SNT. Overall, these findings provide useful information for breeders who are interested in reducing SNT.

Modified dynamic high-frequency ultrasound-guided needle aponeurotomy for Dupuytren's contracture.

The aim of this report was to introduce the use of modified dynamic high-frequency ultrasound-guided needle aponeurotomy for Dupuytren's contracture. From January 2014 to February 2019, the technique was used in 42 consecutive patients who suffered from Dupuytren's contracture: 38 male and 4 female; mean age, 57 years (range, 32-80 years). Assessments comprised total active extension deficit and total active flexion of the fingers, active range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) score, and EQ-5D index. Recurrence was defined as ≥20° flexion contracture. Compared to the opposite hand, preoperative total active extension deficit and total active flexion were 105° ± 32° and 221° ± 33°, respectively. The mean active range of motion of the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints was 42° ± 24°, 37° ± 26° and 62° ± 14°, respectively. Mean follow-up was 27 months (range, 24-35 months). There were no cases of tendon rupture or neurovascular injury. Total active extension deficit and total active flexion at the final follow-up were 17° ± 11° and 225° ± 32°, respectively. The mean active range of motion of metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints was 73° ± 28°, 89° ± 24° and 63° ± 16°, respectively. The pre- and post-operative DASH scores were 18 ± 10 and 5 ± 2, respectively. Health-related quality of life on EQ-5D index improved from 0.72 ± 0.28 pre-operatively to 0.88 ± 0.72 post-operatively (p < 0.05). Recurrence rates in the metacarpophalangeal joint and proximal interphalangeal joint were 7% and 11%, respectively. The modified dynamic high-frequency ultrasound-guided needle aponeurotomy is a safe and effective way to treat Dupuytren's contractures. Ultrasound visualization ensures that the cords can be completely transected. Dynamic ultrasound decreases the risk of iatrogenic injury to the neurovascular bundles and tendons, and decreases the recurrence rate. LEVEL OF EVIDENCE: Therapeutic study, level IV.

[Follow-up analysis on change of serum total cholesterol concentration in rural residents in Shanxi province].

Objective: To analyze the longitudinal change of serum total cholesterol concentration in 733 rural residents in Shanxi province. Methods: Based on the residents of five rural areas in Shanxi province who participated in China nutrition and health survey in 2002, a follow-up survey was conducted in 2015. Fasting venous blood of the participants was collected and serum TC concentration was tested by cholesterol oxidase method. Results: Of 733 participants, 332 were male and 401 were female. In 2002 baseline survey, the age of the participants was (42.6±9.5) years old, 76.2% of male and 83.8% of female had junior middle school education or below. Proportion of smoking were 65.7% and 1.2%, drinking were 26.8% and 4.0%, obesity were 6.3% and 12.0%, and central obesity were 27.1% and 31.9%, respectively in male and female. The follow-up age of participants in 2015 was (55.8±9.5) years old, proportion of smoking changed to 48.2% and 1.5%, drinking were 49.7% and 3.0%, obesity increased to 11.8% and 18.2% and central obesity increased to 41.6% and 53.6%, respectively in male and female. The overall serum TC level increased from (3.82±0.89) mmol/L to (4.72±0.97) mmol/L with an average increase of 27.2%, which increased from (3.84±0.94) mmol/L to (4.54±0.93) mmol/L in male with an average increase of 22.7%, and increased from (3.81±0.84) mmol/L to (4.86±0.98) mmol/L in female with an average increase of 30.9%. The serum TC levels in 18-, 30-, 40-, and 50-59 years old group increased from (3.42±0.83), (3.72±0.77), (3.90±0.83) and (4.00±1.03) mmol/L to (4.38±1.01), (4.79±0.92), (4.73±0.99) and (4.76±0.96) mmol/L, with average increase range of 31.4%, 32.1%, 25.2% and 22.6%, respectively. The mean serum TC levels between two years all had statistically significant difference among groups of gender, age, education, marital status, family history of cardiovascular disease, smoking, drinking, BMI and waist circumference after paired t-test and ANOVA analysis (P<0.01). Conclusion: The longitudinal serum TC level of rural residents in Shanxi province increased rapidly.

Obstetrical outcomes after first-trimester chorionic villus sampling in twin pregnancies: A retrospective case-control study.

AIM: Prenatal diagnostic testing by chorionic villus sampling (CVS) is sometimes recommended for women with twin pregnancies. However, few studies have compared the outcomes between twins with CVS and control twins without intervention. This study aimed to compare the obstetrical outcomes of CVS in twin pregnancies and those in non-intervention twin pregnancies. METHODS: First-trimester transabdominal CVS was performed on dichorionic-diamniotic twins (n = 54; Group 1) between December 2006 and January 2017 at the Department of Obstetrics and Gynecology at our hospital, and the data were retrospectively analyzed. CVS risks were evaluated by comparing obstetrical outcomes with those of a control population of 155 dichorionic-diamniotic twins without intervention (Group 2). RESULTS: The difference in the overall fetal loss rate (Group 1, 7.4% vs Group 2, 3.9%; P = 0.287) between the two groups was not statistically significant. The miscarriage rate, defined as delivery at <24 gestational weeks, and early preterm delivery, defined as delivery at <34 gestational weeks, were not significant between the groups (miscarriage: Group 1, 5.6% vs Group 2, 3.2%; P = 0.428; early preterm delivery: Group 1, 11.1% vs Group 2, 9.0%; P = 0.788). The mean gestational age at delivery, birth weights and neonatal intensive care unit admission rate were not statistically significant between the groups. Thus, the overall fetal loss rate and obstetrical outcomes of Group 1 were comparable with those of Group 2. CONCLUSION: In conclusion, the overall obstetrical outcomes were not significantly different between twins with CVS and control twins with the advantage of enabling early decision-making about selective feticide in twins with CVS.

[Body mass index and related attribution to all-cause mortality in adults of Family Cohort of Nutrition and Chronic Diseases in Shanxi province].

Objective: To assess the relationship between body mass index (BMI) and mortality in adults of Shanxi, China. Methods: Baseline data were from the '2002 China Nutrition and Health Survey' in Shanxi province. All the death-related investigation and follow-up visits were carried out from December 2015 to March 2016. The follow-up program covered 5 360 people from all the 7 007 participants aged 18 years and over that having complete core information, with a rate as 76.5%. Participants of this study were divided into eight groups, according to the appearance of BMI. Taking the group with the lowest mortality density as the reference group, Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of deaths by the whole population, gender and age groups (≥60 years, <60 years). Results were then adjusted by age, gender, smoking, alcohol use and education level from the baseline survey. Sensitivity analysis was also conducted. Results: Results from the study showed that among the total number of 67 129 person- years from the average period of 12.5 years, there were 615 deaths occurred, with the mortality density as 916 per 100 000 person-years. Taking the BMI range of 26.0-27.9 kg/m(2) as the reference, the aHRs of death increased to 1.90 (95%CI: 1.26-2.86), 1.68 (95%CI: 1.15-2.45), 1.49 (95%CI: 1.08-2.06) and 1.72 (95%CI: 1.07-2.76) after the multivariate adjustment, in these four groups (BMI<18.5, 18.5-19.9, 22.0-23.9 and ≥30.0 kg/m(2)), respectively. Low body weight (BMI<18.5 kg/m(2)) was associated with higher risks of death in the elderly of ≥60 years, with the aHR of death as 1.94 (95%CI: 1.20-3.15). Conclusions: When BMI appeared as ≤19.9 kg/m(2), 22.0-23.9 kg/m(2) and ≥30.0 kg/m(2), the risks of death would increase. In addition to programs that focusing on obesity, special attention should be paid to the high risk of mortality which was caused by low-weight and malnutrition in the elderly.

Improvement in postoperative pain control by combined use of intravenous dexamethasone with intravenous dexmedetomidine after interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised controlled trial.

BACKGROUND: Intravenous dexamethasone or dexmedetomidine is reported to prolong the duration of analgesia after single-shot interscalene brachial plexus block (ISBPB). However, the effect of co-administration of these agents on the duration of analgesia has not been evaluated. OBJECTIVES: We evaluated the difference in time to first rescue analgesic request between patients receiving co-administered intravenous dexamethasone and dexmedetomidine and patients receiving intravenous dexamethasone alone after single-shot ISBPB for arthroscopic shoulder surgery. DESIGN: A randomised controlled study. SETTING: A single tertiary care centre, study period from August 2017 to January 2018. PATIENTS: Sixty-six patients undergoing arthroscopic shoulder surgery with ISBPB with 15 ml of 0.5% ropivacaine with 1 : 200 000 epinephrine. INTERVENTIONS: We randomly assigned the patients to one of three groups: intravenous 0.9% saline (control), intravenous dexamethasone 0.11 mg kg (D1 group), or co-administered intravenous dexamethasone 0.11 mg kg and intravenous dexmedetomidine 1.0 µg kg (D2 group). MAIN OUTCOME MEASURES: The primary outcome was the time to first rescue analgesic request. RESULTS: The median [interquartile range] time to first rescue analgesic request was significantly longer for the D2 group (66.3 h [23.3 to 72]) than the D1 (17.4 h [14.9 to 36], P = 0.002) and control (10.9 h [10.1 to 12.2], P < 0.001) groups. The D1 and D2 groups both had reduced pain scores, reduced postoperative opioid consumption, less sleep disruption and improved patient satisfaction compared with the control group. There were no significant elevations in blood glucose concentrations in patients receiving dexamethasone (D1 and D2 groups) compared with the control group at postoperative day 1. CONCLUSION: Co-administration of intravenous dexamethasone (0.11 mg kg) with dexmedetomidine (1.0 µg kg) significantly prolonged the time to first rescue analgesic request after single-shot ISBPB in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0002569.

[Cortical auditory evoked potentials in congenital hearing impaired children with cochlear implants].

OBJECTIVE: By investigating the auditory cortical evoked potential in congenital hearing impaired children with cochlear implants, the association between central auditory development and the age of implantation was studied. METHODS: P1-N1-P2 were recorded in 110 profound hearing impaired children, aged from 12 to 80 months old and being implanted with cochlear implants before the age of 5 years. Their implant using time ranged from just at the switch-on to 48 months. The stimuli were /m/, /t/, /g/, presented at 65 dB SPL in sound field. The presence rate of each wave was obtained and the relationship between P1 latency and implant age, the time of speech processor switch-on were analyzed. RESULTS: The presence rate of P1, N1 and P2 was 66.4%, 15.5% and 12.7%, respectively. The presence of P1 was significantly higher than that of N1(χ(2)=228.542, P=0.00)and P2(χ(2)=257.438, P=0.00). There was no significant difference of P1 presence rate elicited by /m/, /t/ and /g/(64.1%, 66.9% and 68.3%, χ(2)=0.589, P=0.75). There existed no significant difference either among P1 latency(P=0.22)or amplitude(P=0.09) elicited by /m/, /t/ and /g/. There was significant difference between the implant age before and after 42-month-old regarding the proportion that entered the age-appropriate normal P1 latency range(P=0.02). No significant difference was found among groups of implant using time of 1, 2, 3 and 4 years in aspect of the proportion that entered the age-appropriate normal P1 latency range(P=1.00). CONCLUSIONS: Compared with implanted after the age of 42-month-old children with prelingual hearing impairment younger than 5 years old, the ones implanted before 42-month-old have more chance for normal development for central auditory system. Once implanted before 42-month-old, the cortical auditory system restored its normal development as early as 1 year after implantation.

Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism.

Lysosome membrane permeabilization (LMP) mediates cell death in a variety of cancer cells. However, little is known about lysosomes and LMP in chronic lymphocytic leukemia (CLL). Owing to drug resistance and toxicity in CLL patients, better treatment strategies are required. Our results show that CLL cells were sensitive to the lysosomotropic agent siramesine. Furthermore, this drug was more effective in CLL cells, regardless of prognostic factors, compared with normal B cells. Siramesine caused LMP, lipid peroxidation and transcription factor EB nuclear translocation followed by mitochondrial membrane potential loss and reactive oxygen species release. Siramesine-induced cell death was blocked by lipid antioxidants, but not by soluble antioxidants or protease inhibitors. To determine whether CLL cells had altered lysosomes, we investigated sphingolipid metabolism as the lysosome is a hub for lipid metabolism. We found that CLL cells had more lysosomes, increased sphingosine-1-phosphate phosphatase 1 (SPP1) expression, and increased levels of sphingosine compared with normal B cells. Raising sphingosine levels increased LMP and cell death in CLL cells, but not in normal B cells. Together, these results show that excess sphingosine in CLL cells could contribute to their sensitivity toward LMP. Thus, targeting the lysosome could be a novel therapeutic strategy in CLL.

Molecular characterization of the Tobacco rattle virus RNA2 genome isolated from Gladiolus.

Tobacco rattle virus (TRV-K) was first identified in a symptomatic Gladiolus plant cultivated in Korea. We analyzed the TRV-K genome and compared its phylogeny with other TRV isolates. After constructing of a full-length genomic RNA2 strand clone, a complete sequence was generated from several overlapping clones. The cloned genome was 3261 bases in length, identical to TRV-K, and had three open reading frames. TRV-K had the highest sequence identity with the American isolate TRV-ORY. Sequence analysis of the RNA2 genome showed that TRV-K contains an intact 2a, 2b, and 2c coding sequence and an RNA1-related 3' terminus, which is typical of TRV RNA2. Phylogenetic analysis revealed that TRV-K is in the same cluster as the American isolates and another Korean isolate, TRV-SK; however, it was in a different cluster than the European isolates.

Death receptor 6 (DR6) antagonist antibody is neuroprotective in the mouse SOD1G93A model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons, axon degeneration, and denervation of neuromuscular junctions (NMJ). Here we show that death receptor 6 (DR6) levels are elevated in spinal cords from post-mortem samples of human ALS and from SOD1(G93A) transgenic mice, and DR6 promotes motor neuron death through activation of the caspase 3 signaling pathway. Blocking DR6 with antagonist antibody 5D10 promotes motor neuron survival in vitro via activation of Akt phosphorylation and inhibition of the caspase 3 signaling pathway, after growth factor withdrawal, sodium arsenite treatment or co-culture with SOD1(G93A) astrocytes. Treatment of SOD1(G93A) mice at an asymptomatic stage starting on the age of 42 days with 5D10 protects NMJ from denervation, decreases gliosis, increases survival of motor neurons and CC1(+) oligodendrocytes in spinal cord, decreases phosphorylated neurofilament heavy chain (pNfH) levels in serum, and promotes motor functional improvement assessed by increased grip strength. The combined data provide clear evidence for neuroprotective effects of 5D10. Blocking DR6 function represents a new approach for the treatment of neurodegenerative disorders involving motor neuron death and axon degeneration, such as ALS.

A DR6/p75(NTR) complex is responsible for ß-amyloid-induced cortical neuron death.

The p75 neurotrophin receptor (p75(NTR)) is a known mediator of ß-amyloid (Aß)-induced neurotoxicity implicated in Alzheimer's disease (AD). Here, we demonstrate that death receptor 6 (DR6) binds to p75(NTR) and is a component of the p75(NTR) signaling complex responsible for Aß-induced cortical neuron death. Cortical neurons isolated from either DR6 or p75(NTR) null mice are resistant to Aß-induced neurotoxicity. Blocking DR6 function in cortical neurons by anti-DR6 antibodies that block the binding of DR6 to p75(NTR) receptor complex or by a dominant negative DR6 construct lacking the cytoplasmic signaling death domain attenuates Aß-induced caspase 3 activation and cell death. DR6 expression is upregulated in AD cortex and correlates with elevated neuronal death. Targeting the disruption of the DR6/p75(NTR) complex to prevent Aß cytotoxicity represents a new approach for the treatment of neurodegenerative disorders such as AD.

Heritable and non-genetic factors as variables of pharmacologic phenotypes in lymphoblastoid cell lines.

Publicly available genetic and expression data on lymphoblastoid cell lines (LCLs) make them a unique resource for understanding the genetic underpinnings of pharmacological outcomes and disease. LCLs have been used for pharmacogenomic discovery and validation of clinical findings associated with drug response. However, variation in cellular growth rate, baseline Epstein-Barr virus (EBV) copy number and ATP levels can all be confounders in such studies. Our objective is to better define confounding variables that affect pharmacological end points in LCLs. To this end, we evaluated the effect of these three variables on drug-induced cytotoxicity in LCLs. The drugs evaluated included daunorubicin, etoposide, carboplatin, cisplatin, cytarabine, pemetrexed, 5'-deoxyfluorouridine, vorinostat, methotrexate, 6-mercaptopurine, and 5-fluorouracil. Baseline ATP or EBV copy number were not significantly correlated with cellular growth rate or drug-induced cytotoxicity. In contrast, cellular growth rate and drug-induced cytotoxicity were significantly, directly related for all drugs except vorinostat. Importantly, cellular growth rate is under appreciable genetic influence (h²=0.30-0.39) with five suggestive linkage regions across the genome. Not surprisingly, a percentage of SNPs that significantly associate with drug-induced cytotoxicity also associate with cellular growth rate (P ≤ 0.0001). Studies using LCLs for pharmacologic outcomes should therefore consider that a portion of the genetic variation explaining drug-induced cytotoxicity is mediated via heritable effects on growth rate.

The effects of desflurane and sevoflurane on hepatic and renal functions after right hepatectomy in living donors*.

We compared postoperative hepatic and renal functions between the two inhalational anesthetics, desflurane and sevoflurane in living donors undergoing right hepatectomy. Seventy-four adult donors were randomly allocated into Des group (n = 37) and sevo group (n = 37). Before the induction of anesthesia, morphine sulfate 400 microg was injected intrathecally. Anesthesia was maintained with one minimum alveolar concentration (MAC) of deflurane or sevoflurane plus continuous intravenous remifentanil. Liver and renal function tests were performed and analysed at preoperative period, immediately after operation, and on 1st, 2nd, 3rd, 5th, 7th, and 30th postoperative days (PODs). Aspartate aminotransferase (AST) showed significant elevations from the day of surgery to POD 3 and alanine aminotransferase (ALT) was significantly elevated on POD 1 and POD 3 in the sevo group. Albumin level was significantly lower on POD 2 in the sevo group. Creatinine was significantly higher on POD 3 and POD 30 and estimated glomerular filtration ratio was significantly lower on POD 3 and POD 30 in the sevo group. No patient developed hepatic or renal failures. The results of our study showed better postoperative hepatic and renal function test with desflurane than sevoflurane at equivalent dose of 1 MAC in living donors undergoing right hepatectomy, but further study is required to evaluate clinical importance.

Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia.

Development of placentation and successful pregnancy depend on co-ordinated interactions between the maternal decidua and myometrium, and the invasive properties of the fetal trophoblast. Syncytin, a protein encoded by the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W, is highly expressed in placental tissue. Previously, we have shown that the major site of syncytin expression is the placental syncytiotrophoblast, a fused multinuclear syncytium originating from cytotrophoblast cells. Here we present the first evidence that in pre-eclampsia, syncytin gene expression levels are dramatically reduced. Additionally, immunohistochemical examination of normal placentae and placentae from women with pre-eclampsia reveals that the syncytin protein in placental tissue from women with pre-eclampsia is localized improperly to the apical syncytiotrophoblast microvillous membrane as opposed to its normal location on the basal syncytiotrophoblast cytoplasmic membrane. Our previous results suggest that syncytin may mediate placental cytotrophoblast fusion in vivo and may play an important role in human placental morphogenesis. The present study suggests that altered expression of the syncytin gene, and altered cellular location of its protein product, may contribute to the aetiology of pre-eclampsia.

Exogenously regulated stem cell-mediated gene therapy for bone regeneration.

Regulated expression of transgene production and function is of great importance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem cell-based system for controlling bone regeneration, utilizing genetically engineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We show that doxycycline (a tetracycline analogue) is able to control hBMP-2 expression and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, doxycycline administration controlled both bone formation and bone regeneration. Moreover, our findings showed increased angiogenesis accompanied by bone formation whenever genetically engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.

Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis.

Many mammalian viruses have acquired genes from their hosts during their evolution. The rationale for these acquisitions is usually quite clear: the captured genes are subverted to provide a selective advantage to the virus. Here we describe the opposite situation, where a viral gene has been sequestered to serve an important function in the physiology of a mammalian host. This gene, encoding a protein that we have called syncytin, is the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W. We find that the major sites of syncytin expression are placental syncytiotrophoblasts, multinucleated cells that originate from fetal trophoblasts. We show that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibited by an anti-syncytin antiserum. Our data indicate that syncytin may mediate placental cytotrophoblast fusion in vivo, and thus may be important in human placental morphogenesis.

Study on the effects of losartan on cardiomyocyte apoptosis and gene expression after ischemia and reperfusion in vivo in rats.

In order to study the effects of losartan on cardiomyocyte apoptosis following ischemia (0.5 h) and reperfusion (48 h) in vivo and bcl-2 and bax gene expression, TUNEL staining method, immunohistochemistry and in situ hybridization histochemistry (ISHH) were used to monitor the apoptotic cells, mRNA and protein of gene expression, respectively. Image processing system was used to quantitatively dispose the positive metric substance of both immunohistochemistry and ISHH through the average optical density (OD) value. The number of the apoptotic cells were 38 +/- 9 (control group), 0-1 (sham operation group) and 9 +/- 4 (losartan-treated group) in each visual field respectively with the difference among the groups being significant (P < 0.001). OD values of bcl-2 (ISHH) were 0.07425 +/- 0.02029 (control group), 0.05961 +/- 0.009932 (sham operation group) and 0.07619 +/- 0.01445 (losartan-treated group) respectively, while OD values of bcl-2 (immunohistochemistry) were 0.1374 +/- 0.01367 (control group), 0.08510 +/- 0.01862 (sham operation group) and 0.1252 +/- 0.02064 (losartan-treated group). bcl-2 gene expression was increased significantly in the control group and losartan-treated group as compared with sham operation group (P < 0.05). OD value of bax (immunohistochemistry) was 09727 +/- 0.02230 (control group), 0.06182 +/- 0.01430 (sham operation group) and 0.06213 +/- 0.01420 (losartan-treated group). bax gene expression was decreased very significantly in losartan-treated group and sham operation group as compared with control group (P < 0.001). Bcl-2/bax ratio was 1.413 (control group), 1.376 (sham operation group) and 2.016 (losartan-treated group) respectively. The results indicated that losartan might inhibit cardiomyocyte apoptosis following ischemia and reperfusion. The mechanism might be that bax gene expression was inhibited to increase bcl-2/bax ratio.