Effectiveness of integrase strand transfer inhibitors among treatment-naive people living with HIV/AIDS in Guangdong, China: A real-world, retrospective cohort study.

Integrase strand transfer inhibitors (INSTIs) in anti-retroviral therapy (ART) have been recommended by the World Health Organization for their higher efficacy, favorable safety and tolerability. However, the clinical evidence supporting switching to INSTI-containing regimens in low-and-middle-income countries (LMICs) is limited, as few patients have access to these regimens. We aimed to assess the effectiveness of INSTI-containing regimens in real-world settings in China compared to government-provided free ART. We compared the short-term (first 4 mo following ART initiation) and long-term (1 year after ART initiation) effectiveness between INSTI-containing regimens and free ART drugs provided by the Chinese government in 4 dimensions: viral suppression status, immune response, liver and kidney function, and AIDS-related diseases. We obtained data from electronic medical records in the National Infectious Disease Surveillance System. To control baseline confounders, we used propensity score matching (PSM), calculated using logistic regression including socio-demographic and baseline factors. Among 12,836 patients from 2012 to 2019, 673 (5.2%) used INSTI-containing regimens. Patients with INSTI-containing regimens were matched to those with free drugs (644 vs 644). For short-term effectiveness, patients initiating INSTI-containing regimens were more likely to achieve viral suppression (81.4% vs 52.0%; P < .001). The differences in immune response, liver and kidney function and AIDS-related diseases were not significant between the 2 groups. For long-term effectiveness, viral suppression rates were similar (87.96% vs 84.59%; P = .135), with no significant differences in immune response, liver and kidney function, or AIDS-related diseases. Our study suggests that patients initiating ART with INSTI-containing regimens have worse physical status at baseline than patients starting with free ART drugs. Furthermore, we found better virological performances of INSTI-containing regimens in the short-term but not in the long-term due to a high rate of drug changes. Our findings have clinical implications and provide new evidence regarding the effectiveness of INSTI-containing regimens in LMICs.

Lipid metabolism in tumor-infiltrating regulatory T cells: perspective to precision immunotherapy.

Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.

Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Effectiveness of a WHO self-help psychological intervention to alleviate stress among healthcare workers in the context of COVID-19 in China: a randomised controlled trial.

AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.

L-shaped association between the GA/HbA1c ratio and all-cause mortality in U.S. adults with NAFLD: a cross-sectional study from the NHANES 1999-2004.

OBJECTIVE: It is currently unclear whether there is a relationship between the ratio of glycated albumin to hemoglobin A1c (GA/HbA1c) and mortality in individuals diagnosed with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to investigate the relationship between the GA/HbA1c ratio and all-cause mortality in adults with NAFLD in the U.S. METHODS: The investigation included a total of 5,295 individuals aged ≥ 18 years who were diagnosed with NAFLD, these individuals were selected from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. To evaluate the outcomes of death, the researchers relied on National Death Index (NDI) records up to December 31, 2019. To better understand the nonlinear relationship between the GA/HbA1c ratio and mortality among individuals with NAFLD, this study employed both subgroup and sensitivity analyses. Furthermore, Cox proportional hazards models and two-part Cox proportional hazards model were utilized. RESULTS: The study included a total of 5,295 adult patients with NAFLD in the U.S. During a median follow-up period of 16.9 years, there were 1,471 recorded deaths, including 419 cardiovascular deaths. After accounting for various factors, a higher GA/HbA1c ratio exhibited a positive and nonlinear association with an increased risk of all-cause mortality in patients with NAFLD. Furthermore, the study revealed an L-shaped relationship between the GA/HbA1c ratio and all-cause mortality, with the inflection point occurring at a GA/HbA1c ratio of 2.21. When the GA/HbA1c ratio exceeded 2.21, each 1-unit increase in the ratio was associated with a 33% increase in the adjusted hazard ratio (HR 1.33; 95% CI 1.14, 1.60) for all-cause mortality. CONCLUSIONS: A nonlinear correlation between the ratio of GA to HbA1c and all-cause mortality was observed in U.S. adults with NAFLD. In addition, an elevated GA/HbA1c ratio was linked to an increased risk of all-cause mortality in these patients.

Macrophage-derived biomimetic nanoparticles enhanced SDT combined with immunotherapy inhibited tumor growth and metastasis.

Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy.

Pollution characteristics and health risk of sixty-five organics in one drinking water system: PAEs should be prioritized for control.

Currently, a large number of emerging organic contaminants have been detected in domestic and international drinking water systems. However, there are differences among the research methods, which lead to system errors in directly comparing the hazards of different contaminants, so it is difficult to analyze the priority control pollutants and the risk control target in drinking water from previous studies. Therefore, we selected a drinking water treatment plant (DWTP) in the east of China, and detected trihalomethanes (THMs), antibiotics, phthalate esters (PAEs), organophosphate esters (OPEs), per and polyfluoroalkyl substances (PFASs), a total of sixty-five organic contaminants in one batch water sample of four seasons, and carried out the whole process monitoring of "Source water-DWTP-Network-Users", and calculated the health risks of contaminants in tap water. The results showed that DWTP could effectively remove antibiotics and PAEs; the removal rate of coagulation for antibiotics can be up to 47%; the release of PAEs in the plastic water supply pipe leads to a significant increase of the concentrations in the water transportation system, which can reach 2.92 times of that in finished water; compared with other contaminants, THMs and PAEs in tap water have higher health risks. This study reveals that THMs and PAEs are priority control organic pollutants, and the water supply network is the key risk control target in the drinking water system, providing a theoretical basis for how to ensure the safety of drinking water.

Electrochemically Driven Nickel-Catalyzed Halogenation of Unsaturated Halide and Triflate Derivatives.

A robust electrochemically driven nickel-catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2'-bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional-group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates.

Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization.

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.

Temperature-Sensitive Nanocarbon Hydrogel for Photothermal Therapy of Tumors.

Background: Intelligent hydrogels continue to encounter formidable obstacles in the field of cancer treatment. A wide variety of hydrogel materials have been designed for diverse purposes, but materials with satisfactory therapeutic effects are still urgently needed. Methods: Here, we prepared an injectable hydrogel by means of physical crosslinking. Carbon nanoparticle suspension injection (CNSI), a sentinel lymph node imaging agent that has been widely used in the clinic, with sodium ß-glycerophosphate (ß-GP) were added to a temperature-sensitive chitosan (CS) hydrogel (CS/GP@CN) as an agent for photothermal therapy (PTT). After evaluating the rheological, morphological, and structural properties of the hydrogel, we used 4T1 mouse breast cancer cells and B16 melanoma cells to assess its in vitro properties. Then, we intratumorally injected the hydrogel into BALB/c tumor-bearing mice to assess the in vivo PTT effect, antitumor immune response and the number of lung metastases. Results: Surprisingly, this nanocarbon hydrogel called CS/GP@CN hydrogel not only had good biocompatibility and a great PTT effect under 808nm laser irradiation but also facilitated the maturation of dendritic cells to stimulate the antitumor immune response and had an extraordinary antimetastatic effect in the lungs. Discussion: Overall, this innovative temperature-sensitive nanocarbon hydrogel, which exists in a liquid state at room temperature and transforms to a gel at 37 °C, is an outstanding local delivery platform with tremendous PTT potential and broad clinical application prospects.

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis.

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Reperfusion and cytoprotective agents are a mutually beneficial pair in ischaemic stroke therapy: an overview of pathophysiology, pharmacological targets and candidate drugs focusing on excitotoxicity and free radical.

Stroke is the second-leading cause of death and the leading cause of disability in much of the world. In particular, China faces the greatest challenge from stroke, since the population is aged quickly. In decades of clinical trials, no neuroprotectant has had reproducible efficacy on primary clinical end points, because reperfusion is probably a necessity for neuroprotection to be clinically beneficial. Fortunately, the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke (AIS) therapy. Brain cytoprotective agents can prevent detrimental effects of ischaemia, and therefore 'freeze' ischaemic penumbra before reperfusion, extend the time window for reperfusion therapy. Because reperfusion often leads to reperfusion injury, including haemorrhagic transformation, brain oedema, infarct progression and neurological worsening, cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion injuries. Therefore, reperfusion and cytoprotective agents are a mutually beneficial pair in AIS therapy. In this review, we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS, focusing on excitotoxicity and free radicals. We discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials, highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.

Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer.

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Wedge resection versus segment IVb and V resection of the liver for T2 gallbladder cancer: a systematic review and meta-analysis.

Objectives: Although guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver. Methods: A specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted. Results: A total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed. Conclusions: In conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.

High-Resolution Network with Dynamic Convolution and Coordinate Attention for Classification of Chest X-ray Images.

The development of automatic chest X-ray (CXR) disease classification algorithms is significant for diagnosing thoracic diseases. Owing to the characteristics of lesions in CXR images, including high similarity in appearance of the disease, varied sizes, and different occurrence locations, most existing convolutional neural network-based methods have insufficient feature extraction for thoracic lesions and struggle to adapt to changes in lesion size and location. To address these issues, this study proposes a high-resolution classification network with dynamic convolution and coordinate attention (HRCC-Net). In the method, this study suggests a parallel multi-resolution network in which a high-resolution branch acquires essential detailed features of the lesion and multi-resolution feature swapping and fusion to obtain multiple receptive fields to extract complicated disease features adequately. Furthermore, this study proposes dynamic convolution to enhance the network's ability to represent multi-scale information to accommodate lesions of diverse scales. In addition, this study introduces a coordinate attention mechanism, which enables automatic focus on pathologically relevant regions and capturing the variations in lesion location. The proposed method is evaluated on ChestX-ray14 and CheXpert datasets. The average AUC (area under ROC curve) values reach 0.845 and 0.913, respectively, indicating this method's advantages compared with the currently available methods. Meanwhile, with its specificity and sensitivity to measure the performance of medical diagnostic systems, the network can improve diagnostic efficiency while reducing the rate of misdiagnosis. The proposed algorithm has great potential for thoracic disease diagnosis and treatment.

Plasmonic Cavity for Self-Powered Chemical Detection and Performance Boosted Surface-Enhanced Raman Scattering Detection.

With the popularization of the Internet of Things, the application of chemical sensors has become more and more extensive. However, it is difficult for a single functional sensor to meet multiple needs at the same time. For the next generation of chemical sensors, in addition to rapid qualitative and quantitative detection, it is also necessary to solve the problem of a distributed sensor power supply. Triboelectric nanogenerator (TENG) and surface-enhanced Raman scattering (SERS) are two emerging technologies that can be used for chemical testing. The combination of TENG and SERS technology is proposed to be an attractive research strategy to implement qualitative and quantitative analysis, as well as self-powered detection in one device. Herein, the Ag nanoparticle (NP)@polydimethylsiloxane (PDMS) plasmonic cavity is demonstrated, which can be exploited not only as a SERS substrate for qualitative analysis of the target molecules but also as a TENG based self-powered chemical sensor for rapid quantitative analysis. More importantly, the as-designed plasmonic cavity enables prolonged triboelectric field generated by the phenomena of triboelectricity, which in turn enhances the "hot spot" intensities from Ag NPs in the cavity and boosts the SERS signals. In this way, the device can have good feasibility and versatility for chemical detection. Specifically, the measurement of the concentration of many analytes can be successfully realized, including ions and small molecules. The results verify that the proposed sensor system has the potential for self-powered chemical sensors for environmental monitoring and analytical chemistry.

Robot Assisted Laparoscopy Combined with Thoracoscopy in the Treatment of Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus.

BACKGROUND: Facing the 0.7-22% incidence rate of hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT), there are usually no obvious symptoms and signs when the tumor thrombus completely blocks the IVCTT in the early stage.1.J Gastroenterol. 29:41-46;2.Hepatogastroenterology. 41:154-157;3.Clin Cardiol. 19:211-213; Once diagnosed, it is the end-stage manifestation without unified treatment for HCC with IVCTT, bringing poor prognosis. Without active treatment, the median survival time is only 3 months. Previous scholars believed that patients with IVCTT should not adopt active surgical treatment. With the advance of technology, active surgical treatment has significantly lengthened the survival time with IVCTT.4.Ann Surg Oncol. 20:914-22;5.World J Surg Oncol. 11:259;6.Hepatogastroenterology. 58:1694-1699; However, for patients with HCC and IVCTT, open surgery was always selected in the past by opening the diaphragm through the combined thoracoabdominal incision to block the superior and subhepatic vena cava, leading long incision and huge trauma. With the development of minimally invasive techniques, laparoscopy thoracoscopy has showed great advantages in the treatment of HCC with IVCTT. A patient underwent laparoscopic with thoracoscopic resection of tumor and cancer thrombectomy after neoadjuvant therapy and then survived after follow-up.7.Ann Surg Oncol. 29:5548-5549 Therefore, it used as a first reported case of robot-assisted laparoscopic with thoracoscopic treatment of HCC complicated inferior vena cava cancer thrombectomy. METHODS: A 41-year-old man had a liver space-occupying lesion discovered during his medical examination 2 months ago. The diagnosis of HCC with IVCTT was confirmed by enhanced CT and biopsy specimen in the first hospitalization. A combination of TACE, targeted therapy, and immunotherapy plan was applied for the patient after multidisciplinary treatment (MDT). Specifically, Lenvatinib was taken orally 8 mg daily and 160 mg of toripalimab was given intravenously every 3 weeks. His reexamination CT showed that the tumor was more advanced after 2 months of treatment. The surgical operation was performed based on comprehensive consideration. The patient was placed in the left lateral decubitus position, and a thoracoscopic prefabricated the inferior vena cava above diaphragm blocking device was pulled out of the incision. The patient was switched to a supine position with the head of the bed raised 30 degrees. The gallbladder was removed first after entering the abdominal cavity, then prefabricated first hilar blocking band. Sterile rubber glove edges and hemo-lock were used to fabricate the blocking device. The novel hepatic inflow occlusion device is a safe, reliable, and convenient technique that is associated with favorable perioperative outcomes and low risk of conversion.8.Surg Endosc. 34:2807-2813 The liver along the middle hepatic vein was cut to expose the anterior wall of the inferior vena cava, then prefabricated posterior inferior vena cava blocking belt and right hepatic vein blocking belt. Finally, the first portal of liver, right hepatic vein, retrohepatic inferior vena cava, and inferior vena cava above diaphragm were blocked in sequence, so that accomplishing tumor resection and thrombectomy of inferior vena cava. It should be emphasized that before the inferior vena cava is completely sutured, the retrohepatic inferior vena cava blocking device should be released to allow blood flow to flush the inferior vena cava. Moreover, transesophageal ultrasound is required to real-time monitor inferior vena cava blood flow and IVCTT. Some images of the operation are shown in Fig. 1. Fig. 1 (a) Layout of the trocar. ①Make a 3cm small incision between the right anterior axillary line and the midaxillary line, parallel to the fourth and fifth intercostal spaces; a puncture hole in the next intercostal space for endoscope; ②2cm above the intersection of umbilicus horizontal line and axillary front line; ③Intersection of right clavicular midline and umbilical horizontal line; ④Superior margin of umbilicus; ⑤The midpoint of '④ & ⑥'; ⑥2cm below the intersection of left clavicular midline and left costal margin. (b) Prefabricated the inferior vena cava blocking device above diaphragm by thoracoscopic. (c) The smooth tumor thrombus protruding into the inferior vena cava RESULTS: It took 475 min to finish the operation, and the loss of blood was estimated as 300 ml. The patient was discharged from hospital 8 days after the operation without postoperative complication. HCC was confirmed by postoperative pathology. CONCLUSIONS: Robot surgical system reduces the limitations of laparoscopic surgery by offering a stable three-dimensional view, 10-times-enlarged image, restored eye-hand axis, and excellent dexterity with the endowristed instruments, which has several advantages over open operation such as diminished blood loss, reduced morbidity, and shorter hospital stay.9.Chirurg. 88:7-11;10.BMC Surg. 11:2;11.Minerva Chir. 64:135-146; Furthermore, it could favor the operative feasibility of difficult resections reducing the conversion rate and playing a role to extend the indications of liver resection to minimally invasive approaches. It may provide new curative options in patients deemed inoperable with conventional surgery, such as HCC with IVCTT.12.Biosci Trends. 16:178-188;13.J Hepatobiliary Pancreat Sci. 29:1108-1123.

Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection.

BACKGROUND: The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. METHODS: We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease-free survival (DFS), surgery-related outcomes, and surgical approaches were collected. RESULTS: A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p < 0.001). There was no significance in OS (p = 0.790), DFS (p = 0.580), and surgery-related outcomes (all p > 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery-related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). CONCLUSIONS: Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery-related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.