[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

[Therapeutic strategies, practice, and prospect of a clinical cure for chronic hepatitis B in China].

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?

We found that congenital uterine anomalies have a negative impact on reproductive outcome in recurrent-miscarriage couples, being associated with further miscarriage with a normal embryonic karyotype. There has been no study comparing live birth rates between patients with and without surgery. We conducted a prospective study to prove that surgery for a bicornuate or septate uterus might improve the live birth rate. A total of 170 patients with congenital uterine anomalies suffering two or more miscarriages were examined. The live birth rate after ascertainment of anomalies, cumulative live birth rate and infertility rate, were compared between patients with and without surgery. In patients with a septate uterus, the live birth rate (81.3%) at the first pregnancy after ascertainment of anomalies with surgery tended to be higher than that (61.5%) in those without surgery. The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for having a baby, but tended to decrease the preterm birth rate and the low birth weight. The possibility that surgery has benefits for having a baby in patients with a septate uterus suffering recurrent miscarriage could not be excluded.

Interferon-ß gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway.

OBJECTIVE: This study aims to investigate the using of bone marrow mesenchymal stem cells (BMSCs) genetically engineered to produce interferon-ß (IFN-ß) as a gene delivery system to treat hepatocellular carcinoma (HCC) in vitro and in vivo. METHODS: To measure the effects on tumour cell growth in vitro, IFN-ß-producing BMSCs (BMSC/IFN-ß) were co-cultured with the HCC cell line HepG2 and Huh7. Enzyme-linked immunosorbent assay (ELISA) was used to detect the IFN-ß secretion in the BMSC culture condition medium (CM). The effect of BMSC/IFN-ß on HCC cells proliferation was examined both in vitro and in vivo by using MTT, colony formation assay, BrdU staining, cell cycle analysis, and xenografted NOD/SCID mouse tumour model. To examine the impact of BMSC/IFN-ß on the AKT/FOXO3a signalling, RT-PCR and western blotting were performed. RESULTS: The BMSC/IFN-ß cells can stably secrete high levels of IFN-ß. Both MTT and colony forming assay showed that HCC cells had a lower growth rate when cultured in BMSC/IFN-ß-CM as compared with that in BMSC/vector-CM or DMEM culture group. Co-culture with BMSC/IFN-ß-CM dramatically decreased the percentages of cells with incorporated BrdUrd. In BMSC/IFN-ß-CM-treated HCC cells, the proportion of G1-phase cells increased but it decreased in the S phase of the cell. The BMSC/IFN-ß inhibited HCC growth in NOD/SCID mice and proved the survival period of these mice. Compared with the control group, p21 and p27 expression of hepatoma cells increased, whereas cyclin D1 and phosphorylation of Rb expression decreased when co-cultured with BMSC/IFN-ß-CM. It was associated with suppression of Akt activity and enhanced transcriptional activity of FOXO3a. CONCLUSION: The IFN-ß gene-modified BMSCs can effectively inhibit the proliferation of HCC cells in vitro and in vivo through inhibiting AKT/FOXO3a pathway. These results indicate that BMSC/IFN-ß are a powerful anticancer cytotherapeutic tool for HCC.

Effects of freezing rates and cryoprotectant on thermal expansion of articular cartilage during freezing process.

The intact articular cartilage has not yet been successfully preserved at low temperature most likely due to the volume expansion from water to ice during freezing. The objective of this current study focuses on examining thermal expansion behavior of articular cartilage (AC) during freezing from 0 degree C to -100 degree C. Thermo Mechanical Analysis (TMA) was used to investigate the effects of different concentrations of dimethyl sulphoxide (DMSO) (0%, 10%, 30% and 60% v/v) and different freezing rates (1 C/min, 3 C/min and 5 C/min). The results showed that: (1) the inhomogeneous thermal expansion (or contraction) presents due to inhomogeneous water distributions in articular cartilage during freezing, which also may be the most likely reason that the matrix has been damaged in cryopreserved intact articular cartilage; (2) at the phase transition temperature range, the maximum thermal strain change value for 5C/min is approximately 1.45 times than that for 1 C/min, but the maximum thermal expansion coefficient of the later is about six times than that of the former; (3) the thermal expansion coefficient decreases with increasing cooling rate at the unfrozen temperature region, but some opposite results are obtained at the frozen temperature region; (4) the higher the DMSO concentration is, at the phase change temperature region, the smaller the thermal strain change as well as the maximum thermal expansion coefficient are, but DMSO concentration exhibits little effect on the thermal expansion coefficient at both unfrozen and frozen region. Once the DMSO concentration increasing enough, e.g. 60% v/v, the thermal strain decreases linearly and smoothly without any abrupt change due to little or no ice crystal forms (i.e. vitrification) in frozen articular cartilage. This study may improve our understanding of the thermal expansion (or contraction) behavior of cryopreserved articular cartilage and it may be useful for the future study on cryopreservation of intact articular cartilage.

[Summary of community smoking cessation intervention theory].

This paper analyzes the literatures about community-based smoking cessation interventions in recent decades and introduces the effectiveness of cessation interventions developed under different theoretical frameworks applied in the community. Because of the severe smoking prevalence in China and the shortage of existing smoking cessation services, the application of smoking cessation services in reducing the smoking rate in Chinese is discussed to provide a reference for the theoretical framework and practical application of community smoking cessation intervention research in China.

Down-regulation of iASPP in human hepatocellular carcinoma cells inhibits cell proliferation and tumor growth.

The oncoprotein inhibitory member of the ASPP family (iASPP) is a key inhibitor of the p53 tumor suppressor and is upregulated in patients with acute leukemia and breast carcinoma. To investigate the effect of iASPP inhibition on the proliferation of hepatocellular carcinoma cells, a recombinant lentivirus vector expressing a small interfering RNA (siRNA) against iASPP gene expression was constructed and used to infect human hepatocellular carcinoma cells (HepG2 and Hep3B). The results showed that iASPP mRNA and protein levels were significantly down-regulated in both cells infected with the siRNA against iASPP. siRNA-mediated down-regulation of iASPP repressed tumor cell proliferation and colony formation in vitro and induced a growth delay of the tumor in vivo, suggesting that iASPP plays an important role in the proliferation of hepatocellular carcinoma cells. iASPP may be a valuable candidate target gene in hepatocellular carcinoma therapy.

Predictive value of serum-soluble CD154 in fulminant hepatic failure.

The interaction of CD40 with CD154 is a pivotal trigger of immune cascade-inducing acute liver failure, however its clinical significance has not been well studied. The present study aimed to investigate the clinical implications of serum-soluble CD154 (sCD154) levels and the expression of CD40 on monocytes in patients with fulminant hepatic failure (FHF). The results showed that serum sCD154 levels and CD40 expression on monocytes were significantly higher in FHF patients than in acute hepatitis (AH) patients and healthy controls, and were also significantly higher in FHF patients who died, compared with those who survived. We conclude that high serum levels of sCD154 may be linked to fatal outcome in patients with severe liver injury and may be a valuable prognostic marker for survival in patients with FHF.

Genomic analysis of the Hsp70 superfamily in Arabidopsis thaliana.

The Arabidopsis genome contains at least 18 genes encoding members of the 70-kilodalton heat shock protein (Hsp70) family, 14 in the DnaK subfamily and 4 in the Hsp110/SSE subfamily. While the Hsp70s are highly conserved, a phylogenetic analysis including all members of this family in Arabidopsis and in yeast indicates the homology of Hsp70s in the subgroups, such as those predicted to localize in the same subcellular compartment and those similar to the mammalian Hsp110 and Grp170. Gene structure and genome organization suggest duplication in the origin of some genes. The Arabidopsis hsp70s exhibit distinct expression profiles; representative genes of the subgroups are expressed at relatively high levels during specific developmental stages and under thermal stress.

A modelling approach to global nitrate leaching caused by anthropogenic fertilisation.

Water quality associated with nitrate (NO3-) leaching from agricultural soils is an important environmental issue. This paper describes a new modelling approach to quantitatively evaluate the effect of the use of fertilisers on global nitrate leaching. A global process-based simulation model was previously developed for the nitrogen cycle in terrestrial ecosystems, in which soil inorganic nitrogen in the form of ammonium (NH4+) and NO3- was considered. After introducing data on world fertiliser consumption (FAO, 1995) into the steady-state model, the extent of disturbance to the nitrogen cycle caused by fertilisation was calculated. Although fertilisation resulted in an annual increase in net primary production (NPP, represented as carbon) of 18 Gt year-1, NO3- leaching and gaseous losses of nitrogen oxides and ammonia were also accelerated. Most regions with heavy fertiliser application (over 100 kg ha-1 year-1) showed a high annual leaching load equal to or more than 20 kg ha-1 year-1. About 2.5% of the land area occupied by terrestrial ecosystems suffered a serious leaching load of more than 30 kg ha-1 year-1. Of the total amount of applied fertilisers (138 Tg year-1) 19% was lost to NO3- leaching, 8% to gaseous ammonia, and 3% to gaseous nitrogen oxides. The rest was assumed to be fixed in the ecosystems through vegetation uptake.

Characterization of T cell subsets using monoclonal antibodies in nasopharyngeal carcinoma patients.

Peripheral blood T cell subsets from 99 patients with nasopharyngeal carcinoma (NPC), 38 age-matched healthy subjects, and 20 patients with head and neck cancer other than NPC were characterized by reactivity with monoclonal antibodies. Patients with NPC showed much lower values of percentage and absolute number of common T cells (OKT3+) and helper cells (OKT4+) (p less than 0.01) than the control groups. The percentage of suppressor cells (OKT8+) was found to be higher in NPC patients than in healthy persons (p less than 0.001), but the absolute number was still lower in NPC patients. A selective decrease in the ratios of OKT4+ to OKT8+ cells was found in NPC patients (p less than 0.001). The ratios were correlated inversely to the clinical stage (r = 0.294, p less than 0.01). After negative selection by complement-mediated cytolysis, the remaining cells were stimulated with phytohemagglutinin. Net counts of isotope incorporation were smaller in all T cell subsets of NPC patients (p less than 0.001). These data indicate that the depressed cell-mediated immunity in NPC patients is due to inadequate number and functions of T cell subsets and a relative increased proportion of suppressor T cells.

The Fujinon diagnostic fiber optic hysteroscope. Experience with 1,503 patients.

A soft and rigid diagnostic fiber optic hysteroscope (outer diameter, 3.7 mm) was developed. A total of 1,503 women underwent panoramic, televised fiber optic hysteroscopy without cervical dilation. No anesthesia, analgesia or tenaculum was required. No complication was encountered during or after the operation. The procedure is simple, easy and safe, with the operator in a relaxed and comfortable position even when the patient has acute flexion of the uterus. Our clinical results prove that the soft and rigid structure of the fiberscope offers advantages over rigid scopes or conventional fiberscopes with full-length soft, malleable parts.

Hong Kong Chinese women's perception of support from midwives during labour.

OBJECTIVE: to identify what support from midwives hinese women find most helpful in contributing to a positive labour and childbirth experience. DESIGN: a quantitative study using a cross-sectional design was employed. Data were collected using a Chinese language version of the Bryanton Adaptation of Nursing Support in Labor Questionnaire. SETTING: a postnatal ward in a Hong Kong public hospital. PARTICIPANTS: purposive sample of 30 Hong Kong Chinese women, from 24 to 38 hours after delivery. KEY FINDINGS: the category of 'informational support' with the specific behaviour of 'praise' was identified as the most supportive. Tangible support such as 'touching' was considered the least helpful behaviour. IMPLICATIONS FOR PRACTICE: suggestions are made for promoting culturally-sensitive midwifery care for Chinese women to include: 'saving face'; interpreting personal orientation; and supporting Chinese 'hot and cold' beliefs.

Multiphoton confocal microscopy using a femtosecond Cr:forsterite laser.

With its output wavelength covering the infrared penetrating window of most biological tissues at 1,200-1,250 nm, the femtosecond Cr:forsterite laser shows high potential to serve as an excellent excitation source for the multiphoton fluorescence microscope. Its high output power, short optical pulse width, high stability, and low dispersion in fibers make it a perfect replacement for the currently widely used Ti:sapphire laser. In this paper, we study the capability of using a femtosecond Cr:forsterite laser in multiphoton scanning microscopy. We have performed the multiphoton excited photoluminescence spectrum measurement on several commonly used bioprobes using the 1,230 nm femtosecond pulses from a Cr:forsterite laser. Efficient fluorescence can be easily observed in these bioprobes through two-photon or three-photon excitation processes. These results will assist in the selection of dichroic beam splitter and band pass filters in a multiphoton microscopic system. We have also performed the autofluorescence spectrum measurement from chlorophylls in live leaves of the plant Arabidopsis thaliana excited by 1,230 nm femtosecond pulses from the Cr:forsterite laser. Bright luminescence from chlorophyll, centered at 673 and 728 nm, respectively, can be easily observed. Taking advantage of the bright two-photon photoluminescence from chlorophyll, we demonstrated the two-photon scanning paradermal and cross-sectional images of palisade mesophyll cells in live leaves of Arabidopsis thaliana.

[Pharmacokinetic and clinical studies on cefodizime in the field of obstetrics and gynecology].

Pharmacokinetic and clinical studies on cefodizime (THR-221, CDZM) were carried out and the following results were obtained. Concentrations of CDZM in serum and uterine tissues were determined from 38 to 282 minutes after drip infusion of 1 g CDZM. CDZM reached peak level of 25.0 micrograms/g or higher in each tissue during a period of 38 to 83 minutes. Concentrations of CDZM in the dead space exudate after drip infusion of 2 g CDZM were also studied. At 240 minutes after injection, CDZM concentration in exudate reached a peak of 46.88 micrograms/ml. These levels far exceeded MICs of CDZM against major pathogens most often isolated in the field of obstetrics and gynecology. CDZM was administered to 7 patients with their diseases diagnosed as pelvic peritonitis (4 cases) or acute adnexitis (3 cases) at a dose of 2-4 g per day for 6-14. days. Clinical response was good in all cases. Transient elevation of liver function was noticed in 2 cases. No other adverse reactions were noted during the study.

[Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

Fundamental and clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791) were carried out and the following results were obtained. Concentrations of MK-0787 in plasma and uterine tissues were determined at 30 minutes to 390 minutes after the completion of an intravenous drip infusion of 500 mg/500 mg of MK-0787/MK-0791 sodium. Levels of MK-0787 in oviduct, ovary, endometrium, myometrium, uterine cervix and portio vaginalis were 5.1, 5.3, 4.2, 6.6, 5.2 micrograms/g and 6.0 micrograms/g, respectively, at 30 minutes after the completion of the infusion. These levels far exceeded the MICs of MK-0787 against major pathogens (Gram-negative rods and anaerobic bacilli) most often isolated in the field of obstetrics and gynecology. MK-0787/MK-0791 was administered by intravenous drip infusion to 11 patients, including 4 with pelvic peritonitis, 4 with adnexitis and one each with peritonitis, tubo-ovarian abscess, and endometritis, at a dose of 1 g/1 g-1.5 g/1.5 g per day for a period of 4 to 9 days. Clinical response was excellent in 2 and good in 9. No adverse reactions or abnormal laboratory findings were observed in any of the patients.

Clinical applications of a new Fujinon operating fiberoptic hysteroscope.

A soft and rigid operating fiberoptic hysteroscope (4.8 mm outer diameter) was developed by Lin et al., with the support of a Fuji Photo Optical Company. The functional part of the telescope consists of three sections: a soft, flexible front section, a rigid rotating middle section, and a semirigid, self-retaining rear section. With these features, the intrauterine target can be approached easily, directly, and closely, usually without cervical dilation or anesthesia and with the operator in a comfortable position. Clinical applications were divided into four groups: (1) directed biopsy, (2) transcervical tubocornual recanalization for the management of cornual occlusion, (3) hysteroscopic chorionic villus sampling, and (4) the removal of lost IUDs. Experience with 153 procedures is presented. No complications were encountered. The authors conclude that this new hysteroscope is a very useful tool for the treatment of intrauterine lesions, used easily in the office and the operating room alike.

Outcome of removal of intrauterine devices with flexible hysteroscopy in early pregnancy.

Removal of intrauterine devices (IUDs) in early pregnancy, when the IUDs threads are not visible at the cervical canal and the patient wishes to continue her pregnancy, remains a problem. Thirty-three patients using IUDs with nonvisible filaments on examination underwent flexible hysteroscopy for retrieval of the devices and follow-up until delivery. In all cases, hysteroscopies were performed without cervical dilatation and anesthesia. In 30 patients, the devices were found within the uterine cavity, and 28 IUDs were removed. In the remaining 3 patients, no IUD was observed. Twenty-four healthy children have been born. Six other patients requested a dilatation and curettage (D & C) about 1-2 weeks later after successful IUD removal. In 2 women, examinations were done at 22 and 29 weeks antepartum, and these 2 patients were lost to follow up. Operative fiberoptic hysteroscopy is proposed as a useful and effective method of retrieval of IUDs in early pregnancy when the filaments of the IUD are absent.