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Abstract Renal impairment and rhabdomyolysis are rare in transplant patients receiving sirolimus. We report the case of a 54-year-old male who underwent liver transplantation and was initially treated with tacrolimus, mycophenolate mofetil, and glucocorticoids for immunosuppression. After the development of renal dysfunction, tacrolimus was replaced with sirolimus. However, one month after taking sirolimus, the patient’s renal function continued to deteriorate, and rhabdomyolysis developed one and a half months later. Serum analysis indicated high sirolimus concentration, whereas renal histopathology revealed acute tubular injury and interstitial arteriopathy. After reducing the dosage of sirolimus, the patient’s creatine kinase levels returned to normal, and renal function improved. Two years after discharge, the patient’s renal function had recovered. This case highlights the importance of monitoring sirolimus blood concentrations in clinical practice, because elevated drug concentrations can lead to renal dysfunction and rhabdomyolysis as adverse reactions. Further investigations into the pathogenic mechanisms of sirolimus-induced renal dysfunction and rhabdomyolysis may contribute to clinical practice.

Abstract The NK-92MI cell line has displayed significant promise in clinical trials for cancer treatment. However, challenges persist in obtaining sufficient cell quantities and achieving optimal cytotoxicity. The proliferation of natural killer (NK) cells involves the formation of cell aggregates, but excessively large aggregates can impede nutrient and waste transport, leading to reduced cell survival rates. In this study, a custom bioreactor was designed to mimic pseudostatic culture conditions by integrating brief mechanical rotation during a 6-h static culture period. This method aimed to achieve an optimal aggregate size while improving cell viability. The findings revealed a 144-fold expansion of 3D NK-92MI cell aggregates, reaching an ideal size of 80–150 µm, significantly increasing both cell proliferation and survival rates. After 14 days of culture, the NK-92MI cells maintained their phenotype during the subsequent phase of cell activation. Moreover, these cells presented elevated levels of IFN-γ expression after IL-18 activation, resulting in enhanced NK cell-mediated cytotoxicity against K562 cells. This innovative strategy, which uses a closed suspension-based culture system, presents a promising approach for improving cell expansion and activation techniques in immunocellular therapy.

Abstract Objective To investigate the clinical significance of using 3D printing guides in modified unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fractures (OVCF), and to explore a new method for preventing paravertebral vein leakage during PVP in conjunction with a previous study of the optimal puncture-side bone cement/vertebral volume ratio(PSBCV/VV%). Methods This retrospective study analyzed 99 patients who underwent unilateral puncture PVP between January 2023 and December 2023. Patients were divided into a guide plate group (46 patients) and a conventional group (53 patients). The guide plate group underwent modified unilateral puncture PVP with the guidance of 3D printing guides, while the conventional group underwent unilateral puncture PVP using the conventional pedicle approach. The distribution of bone cement, surgical outcomes, and the occurrence of cement leakage into paravertebral veins were observed in both groups. Results The guide plate group had significantly shorter operating time and required fewer fluoroscopies compared to the conventional group. The amount of bone cement volume (BCV) used in the guide plate group was higher, but the amount of bone cement volume on the puncture side(PSBCV), the PSBCV/VV%, and the rate of paravertebral vein leakage were lower in the guide plate group compared to the conventional group (P

Achieving high cell transfection efficiency is essential for various cell types in numerous disease applications. However, the efficient introduction of genes into natural killer (NK) cells remains a challenge. In this study, we proposed a design strategy for delivering exogenous genes into the NK cell line, NK-92, using a modified non-viral gene transfection method. Calcium phosphate/DNA nanoparticles (pDNA-CaP NPs) were prepared using co-precipitation methods and combined with low-voltage pulse electroporation to facilitate NK-92 transfection. The results demonstrated that the developed pDNA-CaP NPs exhibited a uniform diameter of approximately 393.9 nm, a DNA entrapment efficiency of 65.8%, and a loading capacity of 15.9%. Furthermore, at three days post-transfection, both the transfection efficiency and cell viability of NK-92 were significantly improved compared to standalone plasmid DNA (pDNA) electroporation or solely relying on the endocytosis pathway of pDNA-CaP NPs. This study provides valuable insights into a novel approach that combines calcium phosphate nanoparticles with low-voltage electroporation for gene delivery into NK-92 cells, offering potential advancements in cell therapy.

Summary: Background: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. Methods: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. Findings: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. Interpretation: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. Funding: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

Background: To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy. Objectives: Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled. Designs: We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index. Methods: Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted. Results: Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen ( p = 0.018). Conclusion: The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

The harvesting of platelet-rich plasma (PRP) from whole blood based on cell density is a standard procedure that is currently applied to commercially available PRP kits. Leukocytes and erythrocytes, which are closer in density, contaminate a significant amount of PRP products, mostly commercial PRP kits. In this study, we tested membrane filters and PRP products from our prototype PRP kit. We did this by putting a membrane filter with pores of 2 μm in the middle of the tube, which is a new way to separate things based on the cell dimension method (CDM). The evaluations were performed for membrane filter use, hematology analysis, blood smears, viability and cytotoxicity assays, and fibrin structure by scanning electron microscopy (SEM). Compared to the density method (DM), the CDM enables the elimination of a significant number of leukocytes and erythrocytes from the PRPs (CDM-PRP) and a significant increase in the number of platelets compared to the whole blood and DM-PRP. Furthermore, both DM-PRP and CDM-PRP increased the cell viability in L929 cells by adding them at 5% in the culture medium. In addition to CDM-PRP having the lowest cytotoxicity based on the LDH assay, the fibrin structure of CDM-PRP blood clots is characterized by thickness and firmness with a network structure. Thus, we believe that the PRP from the prototype PRP kit meets the requirements as a biomaterial for medical treatments.

Abstract Objectives To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. Methods This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients’ preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. Results There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P

Abstract Background Little is known about the epidemiologic features of syndactyly (SD) in Chinese newborns. Methods Using 2007–2019 data from the Chinese Birth Defects Monitoring Network, we conducted a prevalence analysis on overall, isolated and associated syndactyly according to birth year, maternal age, maternal residence, geographic region and infant sex, with special interests in time trends, perinatal outcomes and clinical phenotypes. Results A total of 13,611 SD cases were identified among 24,157,719 births in the study period, yielding the prevalence of 5.63, 4.66 and 0.97 per 10,000 for overall, isolated, and associated SD, respectively. The prevalence of each type of SD exhibited an upward trend over the period. The prevalence of overall SD varied significantly by maternal residence (urban vs. rural, 6.69/10,000 vs. 4.35/10,000), maternal age (

Abstract Background There is no consensus on whether triplet regimen is better than doublet regimen in the first‐line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. Methods This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non‐inferiority in progression‐free survival (PFS) for XELOX as compared with EOX on an intention‐to‐treat basis. Results Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5‐6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0‐6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812‐1.203; Pnon‐inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health‐related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. Conclusions This non‐inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first‐line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

Abstract Objectives To explore the influencing factors of bone cement leakage in the paravertebral vein after vertebroplasty for the treatment of osteoporotic vertebral compression fractures (OVCFs) and to determine the correlation between the puncture-side bone cement/vertebral body volume ratio and bone cement leakage in the paravertebral vein. Methods This was a retrospective analysis of 495 patients (585 vertebral bodies) with OVCFs treated from August 2018 to May 2021 in our hospital. The patients’ postoperative CT data were imported into Mimics software, and the three-dimensional(3D) reconstruction function was used to calculate the bone cement volume (BCV), puncture-side bone cement volume (PSBCV), and vertebral body volume (VBV); the bone cement/vertebral body volume ratio (BCV/VCV%) and puncture-side bone cement/vertebral body volume ratio (PSBCV/VCV%) were additionally calculated. Sex, Age, Body mass index(BMI), Bone density, BCV, PSBCV, VBV, BCV/VCV%, and PSBCV/VCV were compared between the leakage group and the non-leakage group. Logistic regression analysis was used to assess the correlations between the factors that statistically significantly differed between the two groups and the presence of leakage in the paravertebral veins. A receiver operating characteristic (ROC) curve was used to determine the diagnostic value of the PSBCV/VCV% and to obtain the optional cut-off value. Results A total of 102 males and 393 females with an average age of 72.89 (52 ~ 93) years were included in our study. There were 57 cases of cement leakage (59 vertebral bodies) in the paravertebral vein. There were 438 patients (526 vertebral bodies) without paravertebral cement leakage. Univariate analysis showed that the differences in sex, bone density, PSBCV, and PSBCV/VCV% between the two groups were statistically significant (P

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.

Background & AimsTumor-associated chronic inflammation has been determined to play a crucial role in tumor progression, angiogenesis and immunosuppression. The objective of this study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in perihilar cholangiocarcinoma (pCCA) patients following curative resection.MethodsConsecutive pCCA patients following curative resection at 3 Chinese hospitals between 2014 and 2018 were included. The NLR was defined as the ratio of neutrophil count to lymphocyte count. PLR was defined as the ratio of platelet count to lymphocyte count. The optimal cutoff values of preoperative NLR and PLR were determined according to receiver operating characteristic (ROC) curves for the prediction of 1-year overall survival (OS), and all patients were divided into high- and low-risk groups. Kaplan-Meier curves and Cox regression models were used to investigate the relationship between values of NLR and PLR and values of OS and recurrence-free survival (RFS) in pCCA patients. The usefulness of NLR and PLR in predicting OS and RFS was evaluated by time-dependent ROC curves.ResultsA total of 333 patients were included. According to the ROC curve for the prediction of 1-year OS, the optimal cutoff values of preoperative NLR and PLR were 1.68 and 113.1, respectively, and all patients were divided into high- and low-risk groups. The 5-year survival rates in the low-NLR (

Peripheral nerve injuries are commonly occurring traumas of the extremities; functional recovery is hindered by slow nerve regeneration (

Background & aimThe association of perioperative blood transfusion (PBT) with long-term survival in perihilar cholangiocarcinoma (pCCA) patients after surgical resection with curative intent is controversial and may differ among different stages of the disease. This study aimed to investigate the impact of PBT on long-term survival of patients with different stages of pCCA.MethodsConsecutive pCCA patients from three hospitals treated with curative resection from 2012 to 2019 were enrolled and divided into the PBT and non-PBT groups. Propensity score matching (PSM) was used to balance differences in baseline characteristics between the PBT and non-PBT groups. Kaplan–Meier curves and log-rank test were used to compare overall survival (OS) and recurrence-free survival (RFS) between patients with all tumor stages, early stage (8th AJCC stage I), and non-early stage (8th AJCC stage II-IV) pCCA in the PBT and non-PBT groups. Cox regression analysis was used to determine the impact of PBT on OS and RFS of these patients.Results302 pCCA patients treated with curative resection were enrolled into this study. Before PSM, 68 patients (22 patients in the PBT group) were in the early stage and 234 patients (108 patients in the PBT group) were in the non-early stage. Patients with early stage pCCA in the PBT group had significantly lower OS and RFS rates than those in the non-PBT group. However, there were with no significant differences between the 2 groups with all tumor stages and non-early stage pCCA. After PSM, there were 18 matched pairs of patients with early stage and 72 matched pairs of patients with non-early stage. Similar results were obtained in the pre- and post-PSM cohorts: patients with early stage pCCA in the PBT group showed significantly lower OS and RFS rates than those in the non-PBT group, but there were no significant differences between the 2 groups for patients with all tumor stages and non-early stage pCCA. Cox regression analysis demonstrated that PBT was independently associated with worse OS and RFS for patients with early stage pCCA.ConclusionsPBT had a negative impact on long-term survival in patients with early stage pCCA after curative resection, but not in patients with non-early stage pCCA.

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients.BackgroundDocetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients.MethodsIn this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment.ResultsTotal 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%).ConclusionTX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

Several studies have focused on using cell carriers to solve the problem of mesenchymal stem cell expansion on regenerative medicine. However, the disadvantages of using prolonged enzymatic treatment and low cell harvest efficiency still trouble researchers. In this study, PNIPAAm-immobilized gelatin microspheres (abbreviated as GNMS) were synthesized using a simple power-driven flow-focusing microinjection system. The developed thermosensitive GNMS can allow easier harvesting of cells from the microspheres, requiring only 10 ​min of low-temperature treatment and 5 ​min of trypsin treatment. The developed GNMS was characterized by Fourier-transform infrared spectroscopy, optical microscopy, and scanning electron microscopy. Further, live/dead staining, F-actin staining, and PrestoBlue cell viability assays were used to evaluate cytotoxicity, cell morphology, cell proliferation, and harvest efficiency. The gene expression of stem cell markers was determined by real-time quantitative PCR (Q-PCR) analysis to investigate the stemness and phenotypic changes in Wharton's jelly-derived mesenchymal stem cells. The results showed that the engineered cell-laden thermosensitive GNMS could significantly increase the cell harvest rate with over 99% cell survival rate and no change in the cell phenotype. Thus, the described strategy GNMS could be the suitable 3D cell carriers in the therapeutic application and opens new avenues for regenerative medicine.

Abstract Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)‐immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4‐butanediol diglycidyl ether (BDDE) would encapsulate di(2‐ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP‐containing TGA‐chitosan gel (CT‐D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT‐D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT‐D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA‐immobilized chitosan allows the developed CT‐D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.

BackgroundRecurrence is the main cause of death in perihilar cholangiocarcinoma (pCCA) patients after surgery. Identifying patients with a high risk of recurrence is important for decision-making regarding neoadjuvant therapy to improve long-term outcomes.AimThe objective of this study was to develop and validate a prognostic model to predict recurrence-free survival (RFS) after curative resection of pCCA.MethodsPatients following curative resection for pCCA from January 2008 to January 2016 were identified from a multicenter database. Using random assignment, 70% of patients were assigned to the training cohort, and the remaining 30% were assigned to the validation cohort. Independent predictors of RFS after curative resection for pCCA were identified and used to construct a prognostic model. The predictive performance of the model was assessed using calibration curves and the C-index.ResultsA total of 341 patients were included. The median overall survival (OS) was 22 months, and the median RFS was 14 months. Independent predictors associated with RFS included lymph node involvement, macrovascular invasion, microvascular invasion, maximum tumor size, tumor differentiation, and carbohydrate antigen 19-9. The model incorporating these factors to predict 1-year RFS demonstrated better calibration and better performance than the 8th American Joint Committee on Cancer (AJCC) staging system in both the training and validation cohorts (C-indexes: 0.723 vs. 0.641; 0.743 vs. 0.607).ConclusionsThe prognostic model could identify patients at high risk of recurrence for pCCA to inform patients and surgeons, help guide decision-making for postoperative adjuvant therapy, and improve survival.

Body sculpture is a common method to remove excessive fat. The diet and exercise are the first suggestion to keep body shape; however, those are difficult to keep adherence. Ultrasound has been developed for fat ablation; however, it could only serve as the side treatment along with liposuction. In the study, a sonosensitizer of europium-doped calcium carbonate (CaCO3: Eu) would be synthesized by an eco-method and combined with low-intensity ultrasound for lipolysis. The crystal structure of CaCO3: Eu was identified by x-ray diffractometer (XRD). The morphology of CaCO3: Eu was analyzed by scanning electron microscope (SEM). The chemical composition of CaCO3: Eu was evaluated by energy-dispersed spectrophotometer (EDS) and inductively coupled plasma mass spectrometer (ICP-MS). The electronic diffraction pattern was to further check crystal structure of the synthesized individual grain by transmission electron microscope (TEM). The particle size was determined by Zeta-sizer. Water-soluble tetrazolium salt (WST-1) were used to evaluate the cell viability. Chloromethyl-2′,7′-dichlorofluorescein diacetate (CM-H2DCFDA) and live/dead stain were used to evaluate feasibility in vitro. SD-rat was used to evaluate the safety and efficacy in vivo. The results showed that CaCO3: Eu had good biocompatibility and could produce reactive oxygen species (ROS) after treated with low-intensity ultrasound. After 4-weeks, the CaCO3: Eu exposed to ultrasound irradiation on SD rats could significantly decrease body weight, waistline, and subcutaneous adipose tissue. We believe that ROS from sonoluminescence, CO2-bomb and locally increasing Ca2+ level would be three major mechanisms to remove away adipo-tissue and inhibit adipogenesis. We could say that the combination of the CaCO3: Eu and low-intensity ultrasound would be a non-invasive treatment for the body sculpture.

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta‐analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma.MethodsPhase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all‐grade (grade 1‐5) and high‐grade (grade 3‐5) immune‐related pneumonitis (IRP) were estimated by odds ratios (ORs).ResultsA total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1–5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1–5 IRP. No significant difference in grade 1–5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3‐5 IRP, no statistically significant difference was found among different ICIs-based regimens.ConclusionThese findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.

PurposeTo characterize clinical features and identify baseline prognostic factors for survival in young adults with advanced gastric cancer (YAAGC).Materials and MethodsA total of 220 young inpatients (age less than or equal to 40 years) with an initial diagnosis of advanced gastric cancer were retrospectively enrolled in this study.ResultsOf a consecutive cohort of 220 patients with YAAGC, the median overall survival (OS) time was 16.3 months. One-year survival rate was 43.6% (95% CI: 36.5 to 50.7). In this cohort, a female (71.4%, n = 157) predominance and a number of patients with poorly differentiated tumors (95.9%, n = 211) were observed. In the univariate analysis, OS was significantly associated with neutrophil–lymphocyte ratio (NLR) (≥3.12), hypoproteinemia (

BackgroundHepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).MethodsPatients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.ResultsAmong 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081).ConclusionComparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

Abstract Background Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. Methods We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. Results Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140–3.124), severe agitation (OR 1.846, 95%CL 1.266–2.693), unemployment or retirement (OR 1.614, 95%CL 1.189–2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032–2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436–0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240–0.902) were less likely to be associated with antipsychotic polypharmacy. Conclusion The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of

Background: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear. Methods: In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP). Results: The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 μM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. Conclusion: These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.

Neovascularization (NV) of the cornea disrupts vision which leads to blindness. Investigation of antiangiogenic, slow-release and biocompatible approaches for treating corneal NV is of great importance. We designed an eye drop formulation containing gelatin/epigallocatechin-3-gallate (EGCG) nanoparticles (NPs) for targeted therapy in corneal NV. Gelatin-EGCG self-assembled NPs with hyaluronic acid (HA) coating on its surface (named GEH) and hyaluronic acid conjugated with arginine-glycine-aspartic acid (RGD) (GEH-RGD) were synthesized. Human umbilical vein endothelial cells (HUVECs) were used to evaluate the antiangiogenic effect of GEH-RGD NPs in vitro. Moreover, a mouse model of chemical corneal cauterization was employed to evaluate the antiangiogenic effects of GEH-RGD NPs in vivo. GEH-RGD NP treatment significantly reduced endothelial cell tube formation and inhibited metalloproteinase (MMP)-2 and MMP-9 activity in HUVECs in vitro. Topical application of GEH-RGD NPs (once daily for a week) significantly attenuated the formation of pathological vessels in the mouse cornea after chemical cauterization. Reduction in both vascular endothelial growth factor (VEGF) and MMP-9 protein in the GEH-RGD NP-treated cauterized corneas was observed. These results confirm the molecular mechanism of the antiangiogenic effect of GEH-RGD NPs in suppressing pathological corneal NV.

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China.Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis.Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12–38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09–9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients.Limitations: Cross-sectional design, retrospective recall of suicide attempt data.Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.