Perioperative fluid management for adult cardiac surgery: network meta-analysis pooling on twenty randomised controlled trials.

BACKGROUND: The aim of this study was to evaluate colloids and crystalloids used in perioperative fluid therapy for cardiac surgery patients to further investigate the optimal management strategies of different solutions. METHOD: RCTs about adult surgical patients allocated to receive perioperative fluid therapy for electronic databases, including Ovid MEDLINE, EMBase, and Cochrane Central Register of Controlled Trials, were searched up to February 15, 2023. RESULTS: None of the results based on network comparisons, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay, were statistically significant. Due to the small number of included studies, the results, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, are from the direct comparison. For transfusion of RBCs, significant differences were observed in the comparisons of 3% gelatine vs. 6% HES 200/0.5, 4% albumin vs. 5% albumin, 4% gelatine vs. 5% albumin, 5% albumin vs. 6% HES 200/0.5, and 6% HES 130/0.4 vs. 6% HES 200/0.5. In transfusion of FFP, significant differences were observed in comparisons of 3% gelatine vs. 4% gelatine, 3% gelatine vs. 6% HES 200/0.5, 5% albumin vs. 6% HES 200/0.5, 4% gelatine vs. 5% albumin, 4% gelatine vs. 6% HES 200/0.4, and 6% HES 130/0.4 vs. 6% HES 200/0.5. For urinary output at 24 h after surgery, the results are deposited in the main text. CONCLUSION: This study showed that 3% gelatin and 5% albumin can reduce the transfuse RBC and FFP. In addition, the use of hypertonic saline solution can increase urine output, and 5% albumin and 6% HES can shorten the length of ICU stay. However, none of the perioperative fluids showed an objective advantage in various outcomes, including mortality, transfuse PLA, postoperative chest tube output over the first 24 h following surgery, and length of hospital stay. The reliable and sufficient evidences on the injury of the kidney, including acute kidney injury, serum creatinine, serum microglobulin, and blood urea nitrogen, was still lacking. In general, perioperative fluids had advantages and disadvantages, and there were no evidences to support the recommendation of the optimal perioperative fluid for cardiac surgery.

A hot-Jupiter progenitor on a super-eccentric retrograde orbit.

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.

Structural insights into somatostatin receptor 5 bound with cyclic peptides.

Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/DTrp of pasireotide and SSTR5. Moreover, we find that the Q2.63, N6.55, F7.35 and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

Olfactory preference of the litchi fruit borer for oviposition on two litchi varieties.

BACKGROUND: The litchi fruit borer Conopomorpha sinensis Bradley is a major destructive pest of litchi and longan plants in China, India and South East Asia. Given its strong olfactory-based oviposition behaviour, interfering with the chemical communication between this insect pest and its host plant may serve as a potential control strategy. However, the chemical compounds associated with its egg-laying behaviour remain poorly understood. RESULTS: In this study, we investigated the olfactory preference of female C. sinensis for oviposition on intact mature fruits of the Feizixiao (FZX) and Guiwei (GW) varieties. Results showed that female C. sinensis preferred to lay eggs on FZX compared with GW fruits, and this preference was olfactory-induced. In addition, we identified differences in the chemical composition of the volatile blend and proportions between FZX and GW fruits, with terpenes being the main volatile components contributing to this divergence. Compounds that induced electrophysiological activity in female borers were subsequently screened from FZX. d-Limonene exhibited the strongest oviposition attraction among four candidates. Furthermore, this compound served as a volatile olfactory cue for recognition and orientation in female C. sinensis. CONCLUSION: The results of this study provide a deeper understanding of the olfactory preferences of female C. sinensis for oviposition on specific litchi varieties. © 2024 Society of Chemical Industry.

Dihydroartemisinin-driven selective anti-lung cancer proliferation by binding to EGFR and inhibition of NRAS signaling pathway-induced DNA damage.

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Comparison of indocyanine green and blue-stained glue for preoperative localization for pulmonary nodules.

Background: In patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization. Methods: Consecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used. Results: In total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy. Conclusions: IG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG.

Presurgical computed tomography-guided localization of lung ground glass nodules: comparing hook-wire and indocyanine green.

BACKGROUND: Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs. METHODS: Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques. RESULTS: A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000). CONCLUSIONS: Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.

Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

NBD-based colorimetric and ratiometric fluorescent probe in NIR for bisulfite.

This work presented a FRET-ICT based fluorescent probe (named NTC) composed of coumarin-benzothiazole as the acceptor and 4-nitrobenzo[c][1,2,5] oxadiazole (NBD) as the donor for the detection of SO2 derivatives in NIR. Probe NTC possessed superior performance including selectivity, quickly response toward SO32-/HSO3- and high energy transfer efficiency (94 %). The test strips provided a simple and effective tool in detecting the presence of bisulfite. Besides, NTC was applied to test the sulfur dioxide derivatives in food samples and cells.

Computed Tomography-Based Predictive Model for the Probability of Lymph Node Metastasis in Gastric Cancer: A Meta-analysis.

OBJECTIVES: Whether or not a gastric cancer (GC) patient exhibits lymph node metastasis (LNM) is critical to accurately guiding their treatment and prognostic evaluation, necessitating the ability to reliably predict preoperative LNM status. The present meta-analysis sought to examine the diagnostic value of computed tomography (CT)-based predictive models as a tool to gauge the preoperative LNM status of patients with GC. METHODS: Relevant articles were identified in the PubMed, Web of Science, and Wanfang databases. These studies were used to conduct pooled analyses examining sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values, and area under the curve values were computed for summary receiver operating characteristic curves. RESULTS: The final meta-analysis incorporated data from 15 studies, all of which were conducted in China, enrolling 3,817 patients with GC (LNM+: 1790; LNM-: 2027). The developed CT-based predictive model exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 84% (95% confidence interval [CI], 0.79-0.87), 81% (95% CI, 0.76-0.85), 4.39 (95% CI, 3.40-5.67), and 0.20 (95% CI, 0.16-0.26). The identified results were not associated with significant potential for publication bias ( P = 0.071). Similarly, CT-based analyses of LN status exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 62% (95% CI, 0.53-0.70), 77% (95% CI, 0.72-0.81), 2.71 (95% CI, 2.20-3.33), and 0.49 (95% CI, 0.40-0.61), with no significant risk of publication bias ( P = 0.984). CONCLUSIONS: Overall, the present meta-analysis revealed that a CT-based predictive model may outperform CT-based analyses alone when assessing the preoperative LNM status of patients with GC, offering superior diagnostic utility.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients / 中国药房

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

Indocyanine green-loaded platelet activated by photodynamic and photothermal effects for selective control of wound repair.

OBJECTIVE: Prompt and effective wound repair is an essential strategy to promote recovery and prevent infection in patients with various types of trauma. Platelets can release a variety of growth factors upon activation to facilitate revascularization and tissue repair, provided that their activation is uncontrollable. The present study is designed to explore the selective activation of platelets by photodynamic and photothermal effects (PDE/PTE) as well as the trauma repair mediated by PDE/PTE. MATERIALS AND METHODS: In the current research, platelets were extracted from the blood of mice. Indocyanine green (ICG) was applied to induce PDE/PTE. The uptake of ICG by platelets was detected by laser confocal microscopy and flow cytometry. The cellular integrity was measured by microscopy. The reactive oxygen species (ROS) generation and temperature of platelets were assayed by 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) and temperature detector. The activation of platelets was measured by western blots (WB), dynamic light scattering (DLS), and scanning electron microscopy (SEM). The release of growth factor was detected by enzyme-linked immuno sorbent assay (Elisa), wherein the in vitro cell proliferation was investigated by 5-Ethynyl-2'-deoxyuridine (EDU) assay. The wound infection rates model and histological examination were constructed to assay the ICG-loaded platelet-mediated wound repair. RESULTS: Platelets could load with ICG, a kind of photodynamic and photothermal agent, as carriers and remain intact. Near-infrared (NIR) laser irradiation of ICG-loaded platelets (ICG@PLT) facilitated higher temperature and ROS generation, which immediately activated ICG@PLT, as characterized by increased membrane p-selectin (CD62p), cyclooxygenase-2 (COX-2), thromboxane A2 receptor (TXA2R) expression, elevated hydrated particle size, and prominent aggregation in platelets. Further investigation revealed that massive insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) were released from the activated ICG@PLT, which also promoted the proliferation of endothelial cells and keratinocytes in co-culture. In consequence, activated platelets and increased neovascularization could be observed in rats with wound infection treated by ICG@PLT in the presence of NIR. More impressively, the hydrogel containing ICG@PLT accelerated wound healing and suppressed inflammation under NIR, exhibiting excellent wound repair properties. CONCLUSION: Taken together, the current work identified that platelets could be activated by PDE/PTE and thereby release growth factor, potentiating wound repair in a controlled manner.

Dynamic tear meniscus parameters in complete blinking: insights into dry eye assessment.

AIM: To investigate the relationship between dynamic tear meniscus parameters and dry eye using an automated tear meniscus segmentation method. METHODS: The analysis of tear meniscus videos captured within 5s after a complete blink includes data from 38 participates. By processing video data, several key parameters including the average height of the tear meniscus at different lengths, the curvature of the tear meniscus's upper boundary, and the total area of the tear meniscus in each frame were calculated. The effective values of these dynamic parameters were then linearly fitted to explore the relationship between their changing trends and dry eye disease. RESULTS: In 94.74% of the samples, the average height of central tear meniscus increased over time. Moreover, 97.37% of the samples exhibited an increase in the overall tear meniscus height (TMH) and area from the nasal to temporal side. Notably, the central TMH increased at a faster rate compared to the nasal side with the temporal side showing the slowest ascent. Statistical analysis indicates that the upper boundary curvature of the whole tear meniscus as well as the tear meniscus of the nasal side (2, 3, and 4 mm) aid in identifying the presence of dry eye and assessing its severity. CONCLUSION: This study contributes to the understanding of tear meniscus dynamics as potential markers for dry eye, utilizing an automated and non-invasive approach that has implications for clinical assessment.