[Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids].

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11ß-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Precipitation kinetics, microstructure evolution and mechanical behavior of a developed Al-Mn-Sc alloy fabricated by selective laser melting.

The dynamic metallurgical characteristics of the selective laser melting (SLM) process offer fabricated materials with non-equilibrium microstructures compared to their cast and wrought counterparts. To date, few studies on the precipitation kinetics of SLM processed heat-treatable alloys have been reported, despite the importance of obtaining such detailed knowledge for optimizing the mechanical properties. In this study, for the first time, the precipitation behavior of an SLM fabricated Al-Mn-Sc alloy was systematically investigated over the temperature range of 300-450 °C. The combination of in-situ synchrotron-based ultra-small angle X-ray scattering (USAXS), small angle X-ray scattering (SAXS) and X-ray diffraction (XRD) revealed the continuous evolution of Al6Mn and Al3Sc precipitates upon isothermal heating in both precipitate structure and morphology, which was confirmed by ex-situ transmission electron microscopy (TEM) studies. A pseudo-delay nucleation and growth phenomenon of the Al3Sc precipitates was observed for the SLM fabricated Al-Mn-Sc alloy. This phenomenon was attributed to the preformed Sc clusters in the as-fabricated condition due to the intrinsic heat treatment effect induced by the unique layer-by-layer building nature of SLM. The growth kinetics for the Al6Mn and Al3Sc precipitates were established based on the in-situ X-ray studies, with the respective activation energies determined to be (74 ± 4) kJ/mol and (63 ± 9) kJ/mol. The role of the precipitate evolution on the final mechanical properties was evaluated by tensile testing, and an observed discontinuous yielding phenomenon was effectively alleviated with increased aging temperatures.

Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling.

OBJECTIVE: Calcification serves as a surrogate for atherosclerosis-associated vascular diseases, and coronary artery calcification is mediated by multiple pathogenic factors. Estrogen is a known factor that protects the arterial wall against atherosclerosis, but its role in the coronary artery calcification development remains largely unclear. This study tested the hypothesis that estrogen inhibits coronary artery calcification via the hypoxia-induced factor-1α pathway. METHODS: Eight-week-old healthy female Sprague-Dawley rats were castrated, and vitamin D3 was administered orally to establish. Hypoxia-induced factor-1 inhibitor was administered to test its effect on vascular calcification and expression of bone morphogenetic protein 2 and runt-related transcription factor-2. Vascular smooth muscle cell calcification was induced with CaCl2 in rat aortic smooth muscle cells in the presence or absence of E2(17ß-estradiol) and bone morphogenetic protein 2 siRNA intervention. RESULTS: The estrogen levels in ovariectomized rats were significantly decreased, as determined by ELISA. Expression of hypoxia-induced factor-1α mRNA and protein was significantly increased in vascular cells with calcification as compared to those without calcification (p < 0.01). E2 treatment decreased the calcium concentration in vascular cell calcification and cell calcium nodules in vitro (p < 0.05). E2 also lowered the levels of hypoxia-induced factor-1α mRNA and protein (p < 0.01). Oral administration of the hypoxia-induced factor-1α inhibitor dimethyloxetane in castrated rats alleviated vascular calcification and expression of osteogenesis-related transcription factors, bone morphogenetic protein 2 and RUNX2 (p < 0.01). Finally, bone morphogenetic protein 2 siRNA treatment decreased the levels of p-Smad1/5/8 in A7r5 calcification cells (p < 0.01). CONCLUSION: Estrogen deficiency enhances vascular calcification. Treatment with estrogen reduces the expression of hypoxia-induced factor-1α as well as vascular calcification in rats. The estrogen effects occur in a fashion dependent on hypoxia-induced factor-1α regulation of bone morphogenetic protein-2 and downstream Smad1/5/8.

DNA copy number gain-mediated lncRNA LINC01061 upregulation predicts poor prognosis and promotes papillary thyroid cancer progression.

Several DNA copy number amplifications (CNAs) have been reported in papillary thyroid cancer (PTC). However, the functional role of CNAs in PTC remains very unclear. And whether there is a correlation between long noncoding RNA (lncRNA) and CNA requires to be explored. Here, we identified a novel lncRNA LINC01061. The genomic copy number of LINC01061 is amplified, which leads to its elevated expression level in PTC tissues. Moreover, increased level of LINC01061 was correlated with aggressive clinicopathological characteristics. Functional study indicated that LINC01061 silence significantly inhibited the proliferation, cell-cycle and invasion of PTC cells in vitro and tumor growth in vivo. Mechanistically, we showed that LINC01061 interacted with miR-4316 to promote E2F6 expression. The expression of miR-4316 was downregulated in PTC tissues while that of E2F6 was upregulated. Through rescue assay, we demonstrated that LINC01061 promoted PTC cell proliferation, cell-cycle progression and invasion by regulating miR-4316/E2F6 signaling pathway. In conclusion, our research indicated that LINC01061 might be a target for PTC therapy.

Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma.

BACKGROUND: miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer. METHODS: We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR. RESULTS: Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with ß2M, λ light and κ light chain concentration (r=0.480, p=0.0003; r=0.560, p<0.0001; r=0.560, p<0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r=0.247, p=0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR-4449, λ light chain, and ß2M together, the sensitivity was highest compared with λ light chain or ß2M alone, or combined. CONCLUSIONS: The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.

Binding of B-cell maturation antigen to B-cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways.

B-cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell-activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl-2 protein was up-regulated, and Bax protein was down-regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p-JNK and p-Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM.

Bit1-a potential positive regulator of epithelial-mesenchymal transition in lens epithelial cells.

PURPOSE: Posterior capsule opacification (PCO) is a common postoperative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important initial step of PCO pathogenesis. We have previously shown that Bit1 expresses in rat LECs. In this study, we aim to investigate the role of Bit1 in the EMT of human LECs. METHODS: The expression of Bit1 was firstly detected in human PCO-attached LECs and human lens cell line SRA01/04 by real-time PCR and immunofluorescence staining. The proliferation and migration of Bit1 knockdown SRA01/04 cells were evaluated by cell counting, wound-healing assay, and transwell migration assay. The EMT of LECs was triggered by TGF-ß2, and then the effect of Bit1 on EMT with a key biomarker of α-smooth muscle actin (α-SMA) was analyzed by siRNA knockdown assay, and the reversal of EMT was validated by real-time PCR and western blot. RESULTS: Bit1 was obviously augmented in LECs derived from PCO tissues and Bit1 expressed with high levels in the cytoplasm of cultured SRA01/04 cells. Cell proliferation, invasion, and migration, as well as α-SMA expression, were significantly decreased in Bit1 knockdown SRA01/04 cells. While TGF-ß2 elevated Bit1 and α-SMA expression levels in a dose-dependent manner, with peak levels at 10 ng/ml of TGF-ß2 treatment, suppression of Bit1 in SRA01/04 cells reversed the EMT process. TGF-ß2 induced elevation of α-SMA expression level, as well as migration, and invasion abilities were all suppressed by Bit1 deficiency. CONCLUSIONS: These findings reveal that Bit1 promotes TGF-ß2 induced α-SMA expression and acts as an positive regulator of EMT. Suppressing Bit1 inhibits the proliferation, migration, and EMT of LECs. Bit1 may be a potential novel therapeutic target for the prevention and treatment of PCO.

[Identification of interacting proteins with NF-κB in different status of uterine smooth muscle in labor].

OBJECTIVE: To analyze the differentially expressed proteins which interacted with NF-kappaB in the uterine lower segment smooth muscle tissues under different status of labor onset, and to provide a new foundation on the mechanisms for labor onset.
 Methods: NF-κB P65 protein expression in smooth muscle tissues from the term non-labor group, natural term labor group and drug-induced term labor group was analyzed by Western blot. Co-immunoprecipitation and SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) were performed to detect the proteins interacting with NF-κB p65 in the NF-κB p65 complexes. The components of the complex were identified by LC-ESI-MS/MS (liquid chromatography-tandem electrospray mass spectrometry) and database analysis. The identified differentially expressed proteins were confirmed by Western blot.
 Results: Positive expression of NF-κB was detected in all of the three groups. 10 differentially expressed proteins were identified by LC-ESI-MS/MS in human lower segment myometrium tissues in the term non-labor group and natural term labor group, mean while, 5 differentially expressed proteins were identified in the term non-labor group and the drug-induced labor group. 3 differential expression proteins were detected in all of the 3 groups, including Heat shock 70, Annexin A6 and Desmin, which were verified by Western blot. These proteins were mainly involved in chaperone, signal transduction, cell structure, and energy metabolism process, respectively.
 Conclusion: NF-κB expressed in uterine smooth muscle cells is involved in the process of initiation and regulation of labor onset through a number of proteins relevant to signal transduction, cell structure and energy metabolism.

[Screening time and schedule for outpatients with acute fatty liver of pregnancy].

OBJECTIVE: To identify the screening time and prepare a screening schedule for outpatients with acute fatty liver of pregnancy (AFLP).
 METHODS: AFLP patients who admitted to Xiangya Hospital and the Second Xiangya Hospital, Central South University, Hunan, China between November, 2006 and December, 2013, were retrospectively studied. The diagnosis of 78 AFLP patients met the domestic clinical and laboratory criteria and the Swansea criteria. Clinical and laboratory data obtained on admission were used for analysis. Contrastive analysis was conducted within our data and other large medical centers or general hospitals. 
 RESULTS: The difference between domestic clinical and laboratory criteria and Swansea criteria in diagnosing AFLP patients in the 2 hospitals mentioned above was significant (P<0.05). The maternal mortality was 14.10% (11/78) and perinatal mortality was 17.95 % (14/78). The mean gestational age at delivery was 35.6 weeks. Based on the clinical and laboratory data, more than 85% of AFLP patients showed abnormal levels of transaminase, bilirubin, and white blood cells, as well as coagulation dysfunction. Gastrointestinal symptoms, such as abdominal pain and vomiting, jaundice, renal impairment and ascites or bright liver on ultrasound scan, were showed in 50%-85% of AFLP patients. Less than 50% of patients suffered from low blood sugar, high blood ammonia or hepatic encephalopathy.
 CONCLUSION: The 34th gestation week might be important time for screening AFLP outpatients. Gastrointestinal symptoms, blood routine, liver function, and coagulant function tests are recommended as the first grade screening indicators. Renal function, blood sugar test, and abdominal ultrasound could be the second grade screening indicators for AFLP outpatients.

Prospective echocardiographic assessment of cardiac structure and function in Chinese persons living with HIV.

BACKGROUND: Persons living with human immunodeficiency virus (HIV) are at increased risk of developing cardiovascular disease. Few studies have focused on echocardiographic abnormalities in this population. METHODS: China AIDS Clinical Trial 0810 is a prospective, multicenter cohort study of persons living with HIV (PLWH). We performed an echocardiography substudy of 325 PLWH. We examined the prevalence of left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary arterial hypertension (PAH), and increased left ventricular mass (ILVM) in antiretroviral therapy (ART)-naive PLWH at baseline and week 48 after initiation of ART. RESULTS: Compared with age- and sex-matched healthy controls, PLWH had a higher prevalence of DD (16.5% vs 7.2%, P < .027) and a marginally significant higher prevalence of LVSD (7.3% vs 2.1%, P = .056). The increase in the prevalence of DD from baseline to week 48 in PLWH was marginally significant (P = .056). No significant difference was observed in the prevalence of LVSD, PAH, or ILVM at baseline and week 48 in PLWH. In logistic regression analysis of all participants, age was significantly associated with LVSD; HIV infection, age, and hypertension were associated with DD whereas HIV infection and hypertension were associated with ILVM at baseline. Logistic regression analysis of PLWH showed that only age was significantly associated with LVSD and DD. CONCLUSIONS: The prevalence of echocardiographic abnormalities was significantly higher in ART-naive PLWH than in controls. HIV infection was significantly associated with cardiac abnormalities. No significant change in echocardiographic abnormalities was observed after 48 weeks of ART. Longer-term prospective studies are warranted.

Effect of HSF4b on age related cataract may through its novel downstream target Hif1α.

Our previous study identified five new heat shock factor 4 (HSF4) mutations in 150 age-related cataract (ARC) patients which indicated that HSF4 mutations may be associated with this disease. Hypoxia-inducible factor (Hif1α) is an important downstream target of HSF4b. It has been found that Hif1α play also important roles in cataract development. To identify if HSF4b play it role in cataract development through HIF1α, we transfected SRA01/04 lens epithelial cells with small hairpin RNA of HSF4b and measured expressions Hif1α after transfection. Then, we perform chromatin immunoprecipitation quantitative PCR to see the relationship between HSF4b and HIF1α. We found that HSF4 downregulation led to decrease of HIF1α mRNA expression. Furthermore, we demonstrated by ChIP followed by quantitative PCR (ChIP-qPCR) that these HIF-1α is bound by HSF4b near promoters, not gene bodies.

Expression and prognostic significance of CIP2A in cutaneous malignant melanoma.

OBJECTIVE: We investigated the expression and clinical significance of Cancerous inhibitor of protein phosphatase 2A (CIP2A) in Cutaneous malignant melanoma (CMM). METHODS: CIP2A expression was analyzed by immunohistochemistry and western blot. We tested the invasion and migration capability of A375 cells with Matrigel invasion assay, Scratch migration assay and Matrigel migration assay after down-regulating CIP2A expression using siRNA. RESULTS: CIP2A immunostaining level was correlated with Breslow thickness, Clark's Level and lymphovascular invasion. High-CIP2A expression implied poor survival for patients. Downregulation of CIP2A attenuated metastasis of CMM cells. CONCLUSIONS: CIP2A may serve as a novel marker to predict the prognosis for CMM patients.

Serum 25(OH)D and vitamin D status in relation to VDR, GC and CYP2R1 variants in Chinese.

Previous studies have identified several common genetic variants in VDR, GC and CYP2R1 to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] and vitamin D deficiency in Western populations. We aimed to investigate the associations of these variants with serum levels of 25(OH)D and vitamin D status in 1,199 Chinese. Nine common variants of VDR, GC and CYP2R1 were genotyped using multiple SNaPshot assay, and serum 25(OH)D was detected by radioimmunoassay. The prevalence of vitamin D deficiency (<50 nmol/L) was 38.8%, which is higher in women (46.2%) than in men (34.3%, P<0.0001). The risk alleles of three common variants of GC (rs7041, rs4588, and rs2282679) were significantly associated with a lower serum levels of 25(OH)D (-1.789 ≤ß ≤-3.549, P ≤0.006), while common variants in VDR and CYP2R1 were not associated with serum levels of 25(OH)D after adjusted for covariates (P ≥0.30). None of the nine common variants were associated with the presence of vitamin D deficiency in multivariable adjusted logistic regression analyses (P ≥0.17). Haplotype-based analyses of GC-rs7041 and rs4588 showed that the haplotype Gc2-2 (rs7041 AA and rs4588 TT) had the lowest levels of 25(OH)D compared with other haplotypes that contained at least one copy of Gc1 allele (Ptrend <0.0001). Our results suggest that the common variants of GC are genetic determinants of serum 25(OH)D in Chinese.

Radiocarbon-dated archaeological record of early first millennium B.C. mounted pastoralists in the Kunlun Mountains, China.

Pastoral nomadism, as a successful economic and social system drawing on mobile herding, long-distance trade, and cavalry warfare, affected all polities of the Eurasian continent. The role that arid Inner Asia, particularly the areas of northwestern China, Kazakhstan, and Mongolia, played in the emergence of this phenomenon remains a fundamental and still challenging question in prehistoric archaeology of the Eurasian steppes. The cemetery of Liushiu (Xinjiang, China) reveals burial features, bronze bridle bits, weaponry, adornment, horse skulls, and sheep/goat bones, which, together with paleopathological changes in human skeletons, indicate the presence of mobile pastoralists and their flocks at summer pastures in the Kunlun Mountains, ∼2,850 m above sea level. Radiocarbon dates place the onset of the burial activity between 1108 and 893 B.C. (95% probability range) or most likely between 1017 and 926 B.C. (68%). These data from the Kunlun Mountains show a wider frontier within the diversity of mobile pastoral economies of Inner Asia and support the concept of multiregional transitions toward Iron Age complex pastoralism and mounted warfare.

Laparoscopic Ultrasound-Guided Transcystic Approach for the Treatment of Common Bile Duct Stones.

Background: The treatment of choledocholithiasis with nondilated common bile duct (CBD) is a challenge for surgeons who often choose endoscopic retrograde cholangiopancreatography with laparoscopic cholecystectomy (LC) staging surgery instead of simultaneous laparoscopic CBD exploration with LC because of the small CBD diameter. This study aims to introduce and assess the clinical applicability of a technique we developed to identify and extract CBD stones using laparoscopic ultrasound (LUS). Methods: We retrospectively reviewed surgical procedures and clinical data of 13 patients who underwent LC and CBD exploration using LUS between May 2022 and August 2023. The cystic duct was used for CBD stone removal. Results: Ten patients were successfully treated; 2 patients with residual stones were treated with ursodeoxycholic acid, whereas 1 patient required a microincision near the CBD and choledochoscopy because of stone incarceration in the duodenal papilla. The CBD diameter was 6 mm (5-9 mm). There were less than three CBD stones, with diameters of 2-6 mm; the median operative time was 105 minutes (range, 52-155 minutes). One patient developed postoperative cholangitis. The median postoperative hospital stay was 6 days (3-8 days). The stone clearance rate was 76.9%, and the CBD stone detection rate was 100%. No intraoperative complications, postoperative bile leakage, and mortality occurred. Conclusions: CBD exploration and transcystic stone extraction under LUS guidance are safe and effective approaches for patients with choledocholithiasis; strict control over surgical indications is necessary. This study could provide new strategies for effectively treating choledocholithiasis.

Analysis of Related Influencing Factors of Portal Vein Thrombosis After Hepatectomy.

Purpose: To analyze the related factors of portal vein thrombosis (PVT) after hepatectomy. Methods: A retrospective analysis was made on 1029 patients who underwent partial hepatectomy in the first affiliated Hospital of Chongqing Medical University from March 2018 to March 2023, including PVT group (n = 24) and non-PVT group (n = 1005). The general and clinical data of the two groups were collected. Univariate and multivariate logistic regression analysis was used to analyze the clinical information of the two groups. Result: The proportion of preoperative hepatitis B, liver cirrhosis, ascites, intraoperative blood transfusion, postoperative hemostatic drugs, preoperative prothrombin time, intraoperative portal occlusion time, operation time, international standardized ratio of prothrombin time on the first day after operation, D-dimer on the first day after operation, fibrin degradation products on the first day after operation and postoperative hospital stay in the PVT group were all higher than those in the control group (P < .05). The preoperative platelet and albumin in the PVT group were lower than those in the control group. Intraoperative blood transfusion, liver cirrhosis, ascites, international standardized ratio of postoperative prothrombin time, postoperative fibrin degradation products, hilar occlusion time and albumin were independent risk factors for PVT. Conclusion: There are many influencing factors of PVT after hepatectomy. Clinical intervention should be taken to reduce PVT. Clinical Registration Number: K2023-348.

Benefits of Hypothermic Oxygenated Perfusion Versus Static Cold Storage in Liver Transplant: A Comprehensive Systematic Review and Meta-analysis.

Background: The magnitude of potential benefits that hypothermic oxygenated perfusion (HOPE) may provide for liver transplantation (LT) patients compared to static cold storage (SCS) remains uncertain. In this systematic review and meta-analysis, we aimed to investigate the therapeutic effect that HOPE can offer LT recipients relative to SCS by synthesizing available evidence. Methods: A literature search was conducted in Embase, Medline, Web of Science, and the Cochrane database up to 1 June, 2023. The included studies were pooled for meta-analysis to synthesize their findings. Subgroup analysis was performed to investigate potential differences between HOPE and SCS for specific subgroups. Results: A total of 11 studies comprising 1765 patients were included. Compared with SCS, HOPE was associated with a significant reduction in the incidence of early allograft dysfunction (EAD) (OR: 0.36, 95% CI: 0.26-0.50), as well as a noteworthy decrease in graft loss rate within one year (OR: 0.57, 95% CI: 0.33-0.97) and a lower occurrence of Clavien-Dindo grade IIIa or higher complications (OR: 0.62, 95% CI: 0.43-0.89). Subgroup analysis revealed that HOPE significantly reduced the one-year mortality rate, any biliary complications incidence, and acute rejection of transplanted liver rate in patients who received organs from donation after cardiac death (DCD). Conclusions: HOPE has demonstrated efficacy in reducing the incidence of EAD after LT and shows some potential in diminishing postoperative complications such as biliary complications and acute rejection. This ultimately leads to improved patient prognosis, particularly among those receiving DCD grafts.

Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

Effect of rapamycin-induced tumor vessel thrombosis combined with docetaxel in non-small-cell lung cancer.

Lung cancer remains incurable in many cases despite current chemotherapies. We explored an approach combining a recently described antiangiogenic drug, rapamycin, with standard docetaxel cytotoxic therapy on the growth of non-small-cell lung cancer. Rapamycin alone inhibited tumor growth and upregulated apoptosis, with more pronounced effects when rapamycin and docetaxel were combined. Tumor vessel endothelium damage and thrombosis was evident with rapamycin treatment; this was concomitant with decreased microvessel density. In contrast, docetaxel was not antiangiogenic and did not reduce proliferation in tumors, despite its known cytotoxicity. Our data represent a new promising therapeutic regimen against non-small-cell lung cancer.