Prognostic Significance of Advanced Lung Cancer Inflammation Index, a Nutritional and Inflammation Index, in Patients With Gastrointestinal Cancers: A Meta-analysis.

Previous studies have investigated the prognostic value of the advanced lung cancer inflammation index (ALI) in gastrointestinal (GI) cancers; however, the results are controversial. This meta-analysis aimed to evaluate the prognostic and clinicopathological role of ALI in patients with GI cancers. A systematic search of electronic databases was conducted to evaluate the prognostic and clinicopathological value of ALI in GI cancers. Nine studies comprising 3,750 patients were included in this meta-analysis. The pooled results showed that a low ALI was significantly associated with worse overall survival (OS, hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.53-2.47, P < 0.001, I2 = 63.9%) and disease-free survival/relapse-free survival (DFS/RFS, HR = 1.49, 95% CI = 1.28-1.73, P < 0.001, I2 = 0%) in patients with GI cancers. In addition, decreased ALI correlated with the depth of tumor invasion and presence of distant metastasis and tended to be associated with male sex, high carcinoembryonic antigen levels, lymph node metastasis, and right-sided colon cancer. Low ALI was associated with adverse OS and DFS/RFS in patients with GI cancer. In addition, decreased ALI also correlated with clinicopathological factors, indicating higher stage of the malignancy.

Delivery of WeChat-Based HIV Result e-Reports in Social Networks for Recruitment of High-Risk Population: Baseline Data From a Cluster Randomized Controlled Trial.

BACKGROUND: Disclosure of infectious disease status to social network peers can facilitate reaching and early detection among high-risk populations. In this era of social media, globally, HIV/AIDS represents a high burden of infectious disease. Thus, delivery of an HIV result e-report via social media presents a new approach that has the potential to improve contact with and enrollment of the high-risk population in research studies and routine practice. OBJECTIVE: This study explores the effectiveness and associated factors of a recruitment strategy (ie, WeChat-based HIV e-report delivery in social networks) on the enrollment of men who have sex with men (MSM) for an HIV testing intervention study. METHODS: This was an enrollment result analysis of an ongoing cluster randomized controlled trial (RCT) aiming to promote HIV testing among MSM. Recruitment of potential participants was based on the unit of an egocentric social network, which includes 1 core member (an offline tested ego as the recruiter) and several network members (online alters as network associates). Alters' enrollment and alters' transformation to ego-recruiters (alter-ego) were measured as outcomes. Recruitment outcomes were compared between the exchangeable and regular e-report groups of the RCT. Associated factors of both outcomes were also investigated, including sociodemographic characteristics, health behaviors, social network characteristics, e-report types, and online delivery information. Binary outcomes were modeled using logistic models, with Firth correction for rare events. Qualitative interviews were conducted to understand facilitators and barriers in detail for alter-ego as the subsequent wave's recruiter. RESULTS: The e-report of 1157 egos who tested offline were delivered to 5165 alters in 3 recruitment waves; eventually, 1162 eligible alters enrolled in this RCT (response rate: 22.5%). In the exchangeable e-report group, 544 egos recruited 467 alters, of which 35 alters transformed to alter-egos (7.5%), whereas in the regular e-report group, 613 egos recruited 695 alters, of which 40 alters transformed to alter-egos (5.8%). Alters' enrollment at first wave was associated with a higher number of e-reports being forwarded by the egos. Alters' transformation to alter-egos for the subsequent wave was associated with the exchangeable e-report, higher income, being a Guangzhou resident, unprotected anal intercourse, preferring self-testing, and viewing senders' e-reports frequently. Qualitative interviews revealed that the lack of awareness of e-reports' function and inadequate access to e-reports at offline testing facilities were major barriers to alters' transformation to offline ego-recruiters. CONCLUSIONS: The delivery of e-report was feasible in MSM social network, and the success and sustainability of online recruitment depended on high levels of familiarity among MSM with the digital tool. The HIV e-report exchange mechanism might promote MSM to test HIV offline to get their own e-report for exchange in the community. The e-report provides an innovative recruitment method with great potential to trace direct contacts for infectious diseases studies.

[Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders].

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.

Longitudinal associations between BMI change and the risks of colorectal cancer incidence, cancer-relate and all-cause mortality among 81,388 older adults : BMI change and the risks of colorectal cancer incidence and mortality.

BACKGROUND: It remains controversial whether weight change could influence the risks of colorectal cancer (CRC) and mortality. This study aimed to quantify the associations between full-spectrum changes in body mass index (BMI) and the risks of colorectal cancer (CRC) incidence, cancer-related and all-cause mortality among midlife to elder population. METHODS: A total of 81,388 participants who were free of cancer and aged 55 to 74 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening program were involved. The percentage change of BMI was calculated as (BMI in 2006 - BMI at baseline)/BMI at baseline, and was categorized into nine groups: decrease (≥ 15.0%, 10.0-14.9%, 5.0-9.9%, 2.5-4.9%), stable (decrease/increase < 2.5%), increase (2.5-4.9%, 5.0-9.9%, 10.0-14.9%, ≥ 15.0%). The associations between percentage change in BMI from study enrolment to follow-up (median: 9.1 years) and the risks of CRC and mortality were evaluated using Cox proportional hazard regression models. RESULTS: After 2006, there were 241 new CRC cases, 648 cancer-related deaths, and 2361 all-cause deaths identified. Overall, the associations between BMI change and CRC incidence and cancer-related mortality, respectively, were not statistically significant. Compared with participants whose BMI were stable, individuals who had a decrease in BMI were at increased risk of all-cause mortality, and the HRs were 1.21 (95% CI: 1.03-1.42), 1.65 (95% CI: 1.44-1.89), 1.84 (95% CI: 1.56-2.17), and 2.84 (95% CI: 2.42-3.35) for 2.5-4.9%, 5.0-9.9%, 10.0-14.9%, and ≥ 15.0% decrease in BMI, respectively. An L-shaped association between BMI change and all-cause mortality was observed. Every 5% decrease in BMI was associated with a 27% increase in the risk of all-cause mortality (HR = 1.27, 95% CI: 1.22-1.31, p < 0.001). The results from subgroups showed similar trends. CONCLUSIONS: A decrease in BMI more than 5% shows a significantly increased risk of all-cause mortality among older individuals; but no significant association between increase in BMI and all-cause mortality. These findings emphasize the importance of body weight management in older population, and more studies are warranted to evaluate the cause-and-effect relationship between changes in BMI and cancer incidence/mortality.

Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis.

BACKGROUND: This study investigated the relationship between liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis. We used an acoustic radiation force impulse (ARFI) technique to measure stiffness, and a radio frequency (RF) vascular quantitative ultrasound technique to measure changes in common carotid artery elasticity and vascular function. METHODS: Two-hundred seventeen patients with chronic viral hepatitis caused by either hepatitis B virus (HBV) or hepatitis C virus (HCV) were enrolled. We divided the patients into two groups, one comprising 147 patients with chronic hepatitis B (CHB) (98 men and 49 women, average age 46.5 ± 12.2 years) and another comprising 70 patients with chronic hepatitis C (CHC) (47 men and 23 women, average age 47.6 ± 12.1 years). Additionally, 64 healthy age- and sex-matched participants (43 men and 21 women, average age 47.8 ± 5.1 years) were selected as the control group. The ARFI technique was used to measure liver stiffness and the RF ultrasound technique was used to measure carotid artery elasticity parameters including intima-media thickness (IMT), pulse wave velocity (PWV), arterial wall dilation coefficient (DC), compliance coefficient (CC), sclerosis indices α and ß, and augmentation index (Aix). Clinical indicators, liver stiffness, and carotid artery elasticity parameters were observed and compared between the different age groups to investigate the correlation between carotid artery elasticity parameters and liver stiffness. RESULTS: The ARFI values for the CHB and CHC groups were significantly higher than those for the control group (1.84 ± 0.52 vs. 1.04 ± 0.11 m/s; 1.86 ± 0.37 vs. 1.04 ± 0.11 m/s, respectively; P < 0.001). When compared to the control group, both CHB and CHC groups showed an IMT of the same order, but had significantly higher elasticity parameters, such as α and ß, as well as lower DC and CC values (P < 0.001). The PWV of the CHC group was significantly higher than that of the control group (7.98 ± 1.42 vs. 6.09 ± 0.90 m/s, P < 0.001). In the CHB group, all parameters including ARFI, IMT, PWV, DC, CC, α and ß, were significantly different between the two age groups (P < 0.05). Within the CHC group, all parameters including IMT, PWV, DC, α and ß, were significantly different between the two age groups (P < 0.05), except for ARFI, wherein the difference was not statistically significant. The correlation analysis and stepwise multiple linear regression analysis indicated that for patients with CHB, age was an independent predictor of common carotid artery IMT (R2 = 0.468, F = 54.635, and P < 0.001). For patients with CHC, age and blood sugar were independent predictors of common carotid artery IMT (R2 = 0.465, F = 29.118, and P < 0.001). CONCLUSION: Although based on ARFI and RF ultrasound, the carotid artery IMT in patients with CHB and CHC was not significantly higher than that in the control group, their functional elasticity parameters had already changed. This finding serves as a useful reference for the clinical diagnosis of vascular diseases in patients with viral hepatitis. TRIAL REGISTRATION: ClinicalTrials: ChiCTR1800015859 25/04/2018.

Pif1 is a force-regulated helicase.

Pif1 is a prototypical member of the 5' to 3' DNA helicase family conserved from bacteria to human. It has a high binding affinity for DNA, but unwinds double-stranded DNA (dsDNA) with a low processivity. Efficient DNA unwinding has been observed only at high protein concentrations that favor dimerization of Pif1. In this research, we used single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) to study the DNA unwinding activity of Saccharomyces cerevisiae Pif1 (Pif1) under different forces exerted on the tails of a forked dsDNA. We found that Pif1 can unwind the forked DNA repetitively for many unwinding-rezipping cycles at zero force. However, Pif1 was found to have a very limited processivity in each cycle because it loosened its strong association with the tracking strand readily, which explains why Pif1 cannot be observed to unwind DNA efficiently in bulk assays at low protein concentrations. The force enhanced the unwinding rate and the total unwinding length of Pif1 significantly. With a force of 9 pN, the rate and length were enhanced by more than 3- and 20-fold, respectively. Our results imply that the DNA unwinding activity of Pif1 can be regulated by force. The relevance of this characteristic of Pif1 to its cellular functions is discussed.

Unwinding forward and sliding back: an intermittent unwinding mode of the BLM helicase.

There are lines of evidence that the Bloom syndrome helicase, BLM, catalyzes regression of stalled replication forks and disrupts displacement loops (D-loops) formed during homologous recombination (HR). Here we constructed a forked DNA with a 3' single-stranded gap and a 5' double-stranded handle to partly mimic a stalled DNA fork and used magnetic tweezers to study BLM-catalyzed unwinding of the forked DNA. We have directly observed that the BLM helicase may slide on the opposite strand for some distance after duplex unwinding at different forces. For DNA construct with a long hairpin, progressive unwinding of the hairpin is frequently interrupted by strand switching and backward sliding of the enzyme. Quantitative study of the uninterrupted unwinding length (time) has revealed a two-state-transition mechanism for strand-switching during the unwinding process. Mutational studies revealed that the RQC domain plays an important role in stabilizing the helicase/DNA interaction during both DNA unwinding and backward sliding of BLM. Especially, Lys1125 in the RQC domain, a highly conserved amino acid among RecQ helicases, may be involved in the backward sliding activity. We have also directly observed the in vitro pathway that BLM disrupts the mimic stalled replication fork. These results may shed new light on the mechanisms for BLM in DNA repair and homologous recombination.

[Effects of Gualou Xiebai Banxia decoction on blood lipid content, oxidative stress and ox-LDL/Lox-1 pathway in ApoE-/- mice].

To observe the functions of Gualou Xiebai Banxia decoction（GXBD） on regulating lipid metabolism, anti-oxidation, and interposing ox-LDL/Lox-1 pathway, and to explore its anti-atherosclerosis (AS) mechanisms. AS models were established by using 42 Apo-E-/- male mice with high fat diet. AS model mice were randomly divided into the model group, simvastatin group, and GXBD high and low dose groups. C57BL/6J male mice were used as the normal control group, n=10 and the treatment lasted for 8 weeks. The levels of TC, TG, LDL-C, HDL-C, SOD, MDA, GSH-px, and ox-LDL in blood serum were tested 24 h after the last administration. The changes of aortic tissues structure were observed by HE staining; the expression levels of Lox-1 protein and the expression levels of mRNA were detected by Western blot and PCR respectively.Results showed that the blood lipid levels and MDA, ox-LDL levels in blood serum of model group were significantly higher than those in the normal control group, but SOD, GSH-px levels were significantly lower than those in the normal control group, and the Lox-1 protein and mRNA expression levels were also significantly higher than those in the control group(P<0.05), namely aortic atherosclerosis lesions were obvious in model group.The levels of blood lipid and MDA, ox-LDL of GXBD high and low dose groups and simvastatin group were significantly lower than those in model group, while SOD, GSH-px levels were significantly higher than those in model group, and Lox-1 protein and mRNA expression levels were significantly lower than those in model group(P<0.05), namely the aortic atherosclerosis lesions were significantly relieved. The above results indicated that GXBD was capable of modulating blood lipid, anti-oxidation, and inhibiting the expression of Lox-1, and interposing ox-LDL/Lox-1 pathway in the AS model Apo-E-/- mice, which may be one of the mechanisms of anti-atherosclerosis.

[Effect of tripterygium glycosides and Danshen injection on blood coagulation mechanism in children with allergic purpura nephritis].

To observe the effect of tripterygium glycosides combined with Danshen injection on blood coagulation mechanism in children with allergic purpura nephritis, and investigate its treatment efficacy through a randomized controlled study. The results showed that before treatment, there were no significant differences in levels of D-D, APTT, PT, FIB and PLT between treatment group and control group; while after treatment, there were significant differences in levels of D-D, PT, FIB and PLT between two groups, but no difference in level of APTT. The effective rate was 90.38% in treatment group, significantly higher than 79.25% in the control group. There was no significant difference in incidence of adverse reactions between two groups. The results suggested that tripterygium glycosides combined with Danshen injection can enhance treatment efficacy and improve blood coagulation mechanism of children in the treatment of purpura nephritis, with high safety and no adverse effects.

Cloning and identification of a novel thyroid hormone receptor ß isoform expressed in the pituitary gland.

We have previously identified a novel Trß isoform (TrßΔ) in the rat, in which a novel exon N (108 bps) was found between exon 3 and exon 4 of TrßΔ, which represents the only difference between TrßΔ and Trß1. In this study, we searched for an elongated Trß2-like subtype with one additional exon N. We successfully isolated the entire mRNA/cDNA of a novel elongated Trß2 isoform via PCR in the rat pituitary gland. The mRNA/cDNA was only 108 bps (exon N) longer than that Trß2, and the extension of the sequence was between exon 3 and 4 of Trß. The whole sequence of this novel Trß isoform has been published in NCBI GenBank (HM043807.1); it is named TRbeta2Delta (Trß2Δ). In adult rat pituitary tissue, quantitative real-time RT-PCR analysis showed that the mRNA levels of Trß2Δ and Trß2 were roughly equal (P > 0.05). We cloned, expressed, and purified the His-Trß2Δ protein [recombinant TRß2Δ (rTRß2Δ)]. SDS-PAGE and western blotting revealed that the molecular weight of rTRß2Δ was 58.2 kDa. Using a radioligand binding assay and an electrophoretic mobility shift assay, rTRß2Δ-bound T3 with high affinity and recognized thyroid hormone response element (TRE) binding sites. Finally, in vitro transfection experiments further confirmed that rTRß2Δ binding T3 significantly promotes the transcription of target genes via the TRE. Here, we have provided evidence suggesting that rTRß2Δ is a novel functional TR isoform.

Study on the synthesis, biological activity and spectroscopy of naphthalimide-diamine conjugates.

Eleven novel naphthalimide-diamine conjugates were synthesized and their structures were confirmed by elemental analysis, 1H-NMR, 13C-NMR and MS. Their in vitro antitumor activities were assessed using MTT assays on two cancerous cell lines K562, HCT116, and one normal hepatoma cell line QSG 7701. Compound 7f exhibited potent antitumor activity on HCT116 cells and favorable cell selectivity toward QSG 7701 compared with the positive control, amonafide. Moreover, 7f could block HeG2 cells in the G2/M phase and induce HeG2 cells apoptosis. The interaction of compound 7f with herring sperm DNA was studied by UV/vis absorption and fluorescence spectroscopy under physiological conditions (pH = 7.4). The observed spectral quenching of compound 7f by DNA and the displacement of EB from DNA-EB complex by compound 7f indicated that compound 7f could intercalate into DNA base pairs, which was also corroborated by the effect of KI on compound-DNA interaction. Further caloric fluorescent tests revealed that the quenching mechanism was a static type. Meanwhile, the binding constants, thermodynamic parameters and the effect of NaCl on compound-DNA interaction showed that the type of interaction force was mainly hydrogen bonds and the binding process was driven by hydrogen and van der Waals bonding.

[Identification of main chemical constituents of diterpene lactone effective fraction of Andrographis panniculata by HPLC-DAD/ESI-MS and their preliminary pharmacodynamics research].

OBJECTIVE: To establish an HPLC-DAD/ESI-MS method for quickly identifying chemical constituents in diterpene lactone effective fraction of Andrographis panniculata and to study its pharmacodynamics. METHOD: The separation was performed on an Agilent SB-C18 column (2.1 mm x 150 mm, 5 µm) with a mobile phase of acetonitrile (A) and water (B). The flow rate was maintained at 0.4 mL x min(-1) and detection wavelength was set at 205 nm. The samples were analyzed in positive ion mode, and mass scan range was m/z 50-1 000. Using two kinds of tumor cell lines made living animal models, and studied preliminary pharmacodynamics on anti-tumor aspect. RESULT: Five diterpene lactones in the diterpene lactone effective fraction of A. panniculata could be separated in one run. Pharmacodynamic experiments showed that the effectve fraction had an inhibitory effect on the growth of tumor. CONCLUSION: A rapid and efficient HPLC-ESI-MS method to determine the chemical constituents in diterpene lactone effective fraction of A. panniculata has been established, and the preliminary pharmacodynamics research has been done, which could be used for the quality control and further studies of diterpene lactone effective fraction of A. panniculata in vivo.

Pirarubicin combined with TLR3 or TLR4 agonists enhances anti-tumor efficiency.

BACKGROUND: Triple-negative breast cancer (TNBC) is prone to relapse due to the lack of effective therapeutic targets. Macrophages are the most abundant immune cells in the tumor microenvironment (TME) of breast cancer. Targeting the cross-talk between macrophages and cancer cells provides a more efficient strategy for anti-tumor therapy. Toll-like receptors (TLRs) are important players involved in macrophage activation, and TLR agonists are known to play roles in cancer therapy. However, the combination strategy of TLR agonists with chemotherapy drugs is still not well characterized. METHODS: RT-PCR and Western blot were used to detect the expression of TLRs. The communication between breast cancer cells and macrophages were determined by co-culture in vitro. Tumor cells proliferation and migration were investigated by MTT assay and scratch wound assay. The effects of drug combinations and toxic side effects were assessed by immunohistochemistry and Hematoxylin & Eosin staining. RESULTS: Expression of TLR3 and TLR4 were lower in breast tumor tissues compared with adjacent normal tissues. Patients with higher TLR3 or TLR4 expression levels had a better prognosis than those with lower expression levels. TLR3/4 expression was significantly inhibited when breast cancer cells MDA-MB-231 and E0771 were conditioned-cultured with macrophages in vitro and was also inhibited by pirarubicin (THP). However, the combination of TLR agonists and THP could reverse this response and inhibit the proliferation and migration of breast cancer cells. Additionally, this combination significantly reduced the tumor volume and weight in the murine model, increased the expression of TLR3/4 in mouse breast tumors. CONCLUSIONS: Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.

Sustainable Aerobic Bromination with Controllable Chemoselectivity.

The formation of C-Br(s) is one of the most fundamental reactions in organic synthesis. Oxidative bromination is a "green" way to achieve it. Aerobic bromination has drawn great interest in the past decades, while the poor substrate scope and selectivity, low efficiency, and the use of metal catalyst still confine its application. In this article, we establish a transition-metal-free aerobic bromination promoted by ionic liquid in a catalytic amount with controllable chemoselectivity toward numbers of C-Br(s) formed, and both NaBr/AcOH and HBr(aq) could be used as the bromine source. This methodology shows high efficiency and has a broad substrate scope for various kinds of C-H(s). We also validate this system by the gram-scale (one-pot) synthesis of functional molecules and direct recycle of the catalyst. The possible radical pathway of this catalysis is also presented with evidence.

[Effects of surgical operation on helper-inducer T-lymphocytes in sino-nasal neoplasms patients].

OBJECTIVE: To explore the effects of surgical operation on helper-inducer T-lymphocytes (Th1/Th2) in sino-nasal neoplasms. METHODS: From January 2004 to December 2011, 80 patients with malignant tumor in nasal cavities or sinuses were enrolled as experimental group and another 80 subjects with deflection of nasal septum as control group. The phorbol-12-myristate-13-acetate (PMA)-stimulated peripheral blood mononuclear cells (PBMC) were obtained from both malignant tumor and normal control tissues. And flow cytometry was used to detect the expression percentages of interleukin-4 (IL-4) in Th2 cell and interferon-gamma (IFN-γ) in Th1 cell at pre and post-operation. RESULTS: The preoperative expression percentage of CD3(+) CD8(-) IL-4(+) cell in malignant tumor patients was higher than that in controls (6.6% ± 1.7% vs 2.8% ± 1.7%, P < 0.05) while the expression percentage of CD3(+) CD8(-) IFN-γ(+) cell was lower (18.7% ± 5.7% vs 59.3% ± 1.5%, P < 0.05). The preoperative expression percentage of CD3(+) CD8(-) IL-4(+) cell was higher than that at postoperation (6.6% ± 1.7 %vs 2.8% ± 1.5%, P < 0.05). And the postoperative expression percentage of CD3(+) CD8(-) IFN-γ(+) cell was higher than that at preoperation (54.0% ± 4.0% vs 18.7% ± 5.7%, P < 0.05). CONCLUSION: Surgery may restore the immune balance in patients with malignant tumors in nasal cavities or sinuses.

Application of artificial scaffold systems in microbial metabolic engineering.

In nature, metabolic pathways are often organized into complex structures such as multienzyme complexes, enzyme molecular scaffolds, or reaction microcompartments. These structures help facilitate multi-step metabolic reactions. However, engineered metabolic pathways in microbial cell factories do not possess inherent metabolic regulatory mechanisms, which can result in metabolic imbalance. Taking inspiration from nature, scientists have successfully developed synthetic scaffolds to enhance the performance of engineered metabolic pathways in microbial cell factories. By recruiting enzymes, synthetic scaffolds facilitate the formation of multi-enzyme complexes, leading to the modulation of enzyme spatial distribution, increased enzyme activity, and a reduction in the loss of intermediate products and the toxicity associated with harmful intermediates within cells. In recent years, scaffolds based on proteins, nucleic acids, and various organelles have been developed and employed to facilitate multiple metabolic pathways. Despite varying degrees of success, synthetic scaffolds still encounter numerous challenges. The objective of this review is to provide a comprehensive introduction to these synthetic scaffolds and discuss their latest research advancements and challenges.

Prognostic value of lymphocyte-C-reactive protein ratio in patients with liver cancer: a meta-analysis.

Background: The impact of lymphocyte-C-reactive protein ratio (LCR) on clinical outcomes has been reported in liver cancer such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), but the results remain inconsistent. Methods: We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for relevant studies evaluating the association of LCR with survival outcomes and clinicopathological parameters. Results: Eight studies with 4316 patients were included in this meta-analysis. Low LCR was significantly associated with poor overall survival, disease-free survival/relapse-free survival and disease progression clinicopathological parameters in patients with HCC or ICC. Conclusion: Low pretreatment LCR was an adverse prognostic indicator in patients with HCC or ICC. In addition, it was correlated with clinicopathological parameters indicating a higher stage of malignancy.

Correction: WeChat-Based HIV e-Report, a New Approach for HIV Serostatus Requests and Disclosures Among Men Who Have Sex With Men: Prospective Subgroup Analysis of a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/44513.].

WeChat-Based HIV e-Report, a New Approach for HIV Serostatus Requests and Disclosures Among Men Who Have Sex With Men: Prospective Subgroup Analysis of a Randomized Controlled Trial

BACKGROUND: Requesting and disclosing HIV serostatus is associated with a reduction in HIV transmission among men who have sex with men (MSM). However, the reliability of common methods for HIV serostatus request and disclosure is inadequate. Validated approaches for requesting and disclosing HIV serostatus are necessary. OBJECTIVE: The objective of this study was to investigate the use of the HIV e-report as authentic evidence of HIV serostatus among the MSM community in Guangzhou, China. Additionally, the study aimed to explore its correlation with HIV serostatus requesting and disclosure receiving behavior. METHODS: This study is a subgroup analysis of a cluster randomized controlled trial (RCT) that enrolled 357 participants during the first year. Participants in this RCT were recruited from the WeChat-based HIV testing service miniprogram developed by Guangzhou Center for Disease Control and Prevention, China. Participants completed web-based questionnaires at baseline and at the month 3 follow-up, which covered sociodemographic characteristics, HIV-related information, HIV serostatus requests, receiving HIV serostatus disclosures, and HIV e-report usage. Univariate and multivariate logistic regressions were used for data analysis. RESULTS: The WeChat-based HIV e-report was available in Guangzhou when the RCT project started. At the month 3 follow-up, 32.2% (115/357) of participants had their own HIV e-reports, and 37.8% (135/357) of them had received others' HIV e-reports. In all, 13.1% (27/205) and 10.5% (16/153) of participants started to use HIV e-reports to request the HIV serostatus from regular and casual male sex partners, respectively. Moreover, 27.3% (42/154) and 16.5% (18/109) of the regular and casual male sex partners, respectively, chose HIV e-reports to disclose their HIV serostatus. Compared to MSM who did not have HIV e-reports, those who had HIV e-reports and stated, "I had had my own HIV e-report(s) but hadn't sent to others" (multivariate odds ratio 2.71, 95% CI 1.19-6.86; P=.02) and "I had had my own HIV e-reports and had sent to others" (multivariate odds ratio 2.67, 95% CI 1.07-7.73; P=.048) were more likely to request HIV serostatus from their partners. However, no factor was associated with receiving an HIV serostatus disclosure from partners. CONCLUSIONS: The HIV e-report has been accepted by the MSM community in Guangzhou and could be applied as a new optional approach for HIV serostatus requests and disclosures. This innovative intervention could be effective in promoting infectious disease serostatus disclosure among the related high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03984136; https://clinicaltrials.gov/show/NCT03984136. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12879-021-06484-y.

COX-2-independent induction of apoptosis by celecoxib and polyamine naphthalimide conjugate mediated by polyamine depression in colorectal cancer cell lines.

BACKGROUND: Polyamine metabolism is an intriguing tumor therapeutic target. The present study was designed to assess the synergistic antitumor effects of NPC-16, a novel polyamine naphthalimide conjugate, with celecoxib and to elucidate the mechanism of these effects on human colorectal cancer cells. METHODS: Cell proliferation was assessed by the MTT assay. Cell apoptosis and mitochondria membrane potential were evaluated by high content screening analysis. Intracellular polyamine content was detected by HPLC. Protein expression was detected by western blot analysis. RESULTS: The co-treatment with celecoxib enhanced NPC-16-induced apoptosis in HCT116 (COX-2 no expression), HT29 (COX-2 higher expression) and Caco-2 (COX-2 higher expression) colorectal cancer cells, which was mediated by the elevated NPC-16 uptake via the effect of celecoxib on polyamine metabolism, including the up-regulated spermidine/spermine N(1)-acetyltransferase (SSAT) activity and reduced intracellular polyamine levels. The presence of celecoxib does not result in obviously different effect on the NPC-16-triggered apoptosis in diverse COX-2 expressed colorectal cell lines, suggesting that COX-2 was not one vital factor in the apoptotic mechanism. Furthermore, this synergistic apoptosis was involved in the PKB/AKT signal pathway, Bcl-2 and caspase family members. Z-VAD-FMK, a cell permeable pan caspase inhibitor, almost completely inhibited celecoxib and NPC-16 co-induced apoptosis, indicating that this apoptosis was caspase dependent. CONCLUSIONS: Co-treatment of celecoxib and NPC-16 could induce colorectal cancer cell apoptosis via COX-2-independent and caspase-dependent mechanisms. The combination therapy with these agents might provide a novel therapeutic model for colorectal cancer.