Cadmium in Market Pork Kidneys: A Study on Cadmium Bioavailability and the Health Effects Based on Mouse Models.

Edible offal of farmed animals can accumulate cadmium (Cd). However, no studies have investigated Cd bioavailability and its health effects. Here, based on mouse models, market pork kidney samples exhibited high Cd relative bioavailability of 74.5 ± 11.2% (n = 26), close to 83.8 ± 7.80% in Cd-rice (n = 5). This was mainly due to high vitamin D3 content in pork kidney, causing 1.7-2.3-fold up-regulated expression of duodenal Ca transporter genes in mice fed pork kidney compared to mice fed Cd-rice, favoring Cd intestinal absorption via Ca transporters. However, although pork kidney was high in Cd bioavailability, subchronic low-dose (5% in diet) consumption of two pork kidney samples having 0.48 and 0.97 µg Cd g-1 dw over 35 d did not lead to significant Cd accumulation in the tissue of mice fed Cd-free rice but instead remarkably decreased Cd accumulation in the tissue of mice fed Cd-rice (0.48 µg Cd g-1) by ∼50% and increased abundance of gut probiotics (Faecalibaculum and Lactobacillus). Overall, this study contributed to our understanding of the bioavailability and health effects associated with Cd in edible offal, providing mechanistic insights into pork kidney consumption safety based on Cd bioavailability.

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Fear of cancer recurrence in adolescent patients with malignant bone tumors: a cross-section survey.

BACKGROUND: Adolescent malignant-bone tumor patients' fear of cancer recurrence is a significant psychological issue, and exploring the influencing factors associated with fear of cancer recurrence in this population is important for developing effective interventions. This study is to investigate the current status and factors influencing fear of cancer recurrence (FCR) related to malignant bone-tumors in adolescent patients, providing evidence for future targeted mental health support and interventions. DESIGN: A cross-sectional survey. METHODS: In total, 269 adolescent malignant-bone tumor cases were treated at two hospitals in Zhejiang Province, China from January 2023 to December 2023. Patients completed a General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Family Hardiness Index (FHI), and a Simple Coping Style Questionnaire (SCSQ). Univariate and multivariable logistic regressions analysis were used to assess fear of cancer recurrence. RESULTS: A total of 122 (45.4%) patients experienced FCR (FoP-Q-SF ≥ 34). Logistic regression analysis analyses showed that per capita-monthly family income, tumor stage, communication between the treating physician and the patient, patient's family relationships, family hardiness a positive coping score, and a negative coping score were the main factors influencing FCR in these patients (P < 0.05). CONCLUSIONS: FCR in malignant-bone tumor adolescent patients is profound. Healthcare professionals should develop targeted interventional strategies based on the identified factors, which affect these patients; helping patients increase family hardiness, helping patients to positively adapt, and avoid negative coping styles.

Safety profiles of offspring born from early-follicular long-acting GnRH agonist protocol and daily mid-luteal GnRH agonist protocol: a retrospective study.

BACKGROUND: The gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols. METHODS: We conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed. RESULTS: The EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72-4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies. CONCLUSION: In conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.

Glutathionylation of a glycolytic enzyme promotes cell death and vigor loss during aging of elm seeds.

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial proapoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N,N,N',N'-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a proapoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

[Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy].

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Effect of body mass index on the cumulative live birth rate over multiple complete IVF cycles in women with polycystic ovary syndrome: A retrospective study.

OBJECTIVE: The purpose of this study was to investigate the effect of body mass index (BMI) before treatment on the cumulative live birth rate (CLBR) over multiple complete in vitro fertilization (IVF) cycles in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: This study is a single-center retrospective cohort study. It included 5016 patients with PCOS who started their first IVF cycle in our hospital between 2009 and 2018. Kaplan-Meier and log-rank tests were used for the comparison of CLBR across BMI groups. Univariate, multivariate models and stratification analysis were used to evaluate possible influencing factors of CLBR. Smoothing curve fitting was applied to present the correlation between BMI and CLBR. A one-line linear regression model was compared with a two-piecewise linear model using a log-likelihood ratio test. RESULTS: During the 8-year follow-up, 3604 women (71.85%) obtained at least one live birth. The study population was grouped according to BMI, with BMI ranging from [14.53-23.00) kg/m2 in the normal weight group, [23.00-27.50) kg/m2 in the overweight group, and [27.50-37.80] kg/m2 in the obese group, respectively. The CLBR of the obese group and the overweight group were significantly lower than the normal weight group. In the multivariate regression model, HR for CLBR was 0.86 [95%CI: 0.78-0.95] for the obese group, and 0.93 [0.86-1.00] for the overweight group, compared with the normal weight group as control. The curve fitting after adjustment for confounding factors and log-likelihood ratio test showed a one-line linear negative correlation between BMI and CLBR. CONCLUSION: We concluded that the BMI of PCOS patients had a negative one-line linear correlation with CLBR over multiple complete cycles.

Approach to Chemically Durable Nickel and Cobalt Lanthanum-Nitride-Based Catalysts for Ammonia Synthesis.

Metal nitride complexes have recently been proposed as an efficient noble-metal-free catalyst for ammonia synthesis utilizing a dual active site concept. However, their high sensitivity to air and moisture has restricted potential applications. We report that their chemical sensitivity can be improved by introducing Al into the LaN lattice, thereby forming La-Al metallic bonds (La-Al-N). The catalytic activity and mechanism of the resulting TM/La-Al-N (TM=Ni, Co) are comparable to the previously reported TM/LaN catalyst. Notably, the catalytic activity did not degrade after exposure to air and moisture. Kinetic analysis and isotopic experiment showed that La-Al-N is responsible for N2 absorption and activation despite substantial Al being introduced into its lattice because the local coordination of the lattice N remained largely unchanged. These findings show the effectiveness of metallic bond formation, which can support the chemical stability of rare-earth nitrides with retention of catalytic functionality.

IgG subclass deposition in diabetic nephropathy.

PURPOSE: This study aimed to analyze the distribution of IgG subclass in diabetic nephropathy (DN) and its association with clinicopathological features. METHODS: This is a single-center retrospective study enrolling 108 patients with biopsy-proven DN. Immunofluorescence and immunohistochemistry staining were applied, and clinicopathological features and renal outcomes were compared between patients with different patterns or categories of IgG subclass deposition. RESULTS: Both IgG and its subclasses colocalized with collagen IV α5 on glomerular basement membrane (GBM) and some of tubular basement membrane (TBM). IgG1 and the Mixed type were two predominant types of deposition, no matter on GBM or TBM, and IgG1 showed a much higher deposition rate on GBM than that on TBM (P = 0.004). IgG subclass deposit on multi-location was more associated with a shorter duration of nephropathy and severer tubular interstitial injury (P < 0.05). The mixed type of IgG subclass deposit on GBM was merely associated with higher levels of proteinuria, whereas the deposition on TBM was more associated with higher levels of proteinuria, lower levels of albumin, more KIM-1 positive area, and thicker TBM (P < 0.05). Survival analysis revealed that none of the pattern or the category of IgG subclass deposit was a risk factor or a renal outcome indicator. CONCLUSIONS: IgG subclass was selectively deposited along GBM and/or TBM in DN, and the mixed type of IgG subclass deposition on TBM had more clinical significance than the isotype and that on GBM. IgG subclass deposition is merely a manifestation or a consequence rather than a cause in DN.

Prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms: a multi-center study in China.

Background: The incidence of poorly differentiated gastric neuroendocrine neoplasms (G-NENs) has been increasing during the past decades. Methods: A total of 183 patients diagnosed with poorly differentiated G-NENs were enrolled from eight hospitals during 2010-2019 in China. All cases included have accepted abdominal surgery in tertiary hospitals. Result: T3 (HR: 2.66, p = 0.019), T4 (HR: 3.62, p = 0.005), stage IV (HR: 5.67, p < 0.001), vascular invasion (HR: 1.59, p = 0.048) were independent risk factors for poor prognosis of poorly differentiated G-NENs. In stratified analysis, for patients with stage III tumors, those treated with chemotherapy had significantly longer survival than those accepting surgery alone. Conclusion: T3/T4 stage, TNM stage IV and vascular invasion were independent negative prognostic factors for patients with poorly differentiated G-NENs. Patients with stage III tumors can benefit from chemotherapy. Highly selected patients with stage IV tumors may also benefit from surgery.

This study mainly describes a rare cancerous gastric tumor. Numerous people have been diagnosed with this disease during the past decades. Owing to the small number of patients diagnosed with this disease, the treatment method is still not clear. In our study, we found that the outcome of patients who were diagnosed at late stage was much poorer than those diagnosed at early stage. So, it is important for patients to get accurate diagnosis in time. For a part of patients accepting surgery, they may benefit from chemotherapy.

The Role of TAK1 in RANKL-Induced Osteoclastogenesis.

Bone remodelling is generally a dynamic process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts are the only cell type capable of bone resorption to maintain bone homeostasis in the human body. However, excessive osteoclastogenesis can lead to osteolytic diseases. The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) has been widely considered to be an important modulator of osteoclastogenesis thereby participating in the pathogenesis of osteolytic diseases. Transforming growth factor ß-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is an important intracellular molecule that regulates multiple signalling pathways, such as NF-κB and mitogen-activated protein kinase to mediate multiple physiological processes, including cell survival, inflammation, and tumourigenesis. Furthermore, increasing evidence has demonstrated that TAK1 is intimately involved in RANKL-induced osteoclastogenesis. Moreover, several detailed mechanisms by which TAK1 regulates RANKL-induced osteoclastogenesis have been clarified, and some potential approaches targeting TAK1 for the treatment of osteolytic diseases have emerged. In this review, we discuss how TAK1 functions in RANKL-mediated signalling pathways and highlight the significant role of TAK1 in RANKL-induced osteoclastogenesis. In addition, we discuss the potential clinical implications of TAK1 inhibitors for the treatment of osteolytic diseases.

Deep learning based cervical screening by the cross-modal integration of colposcopy, cytology, and HPV test.

PURPOSE: To develop and evaluate the colposcopy based deep learning model using all kinds of cervical images for cervical screening, and investigate the synergetic benefits of the colposcopy, the cytology test, and the HPV test for improving cervical screening performance. METHODS: This study consisted of 2160 women who underwent cervical screening, there were 442 cases with the histopathological confirmed high-grade squamous intraepithelial lesion (HSIL) or cancer, and the remained 1718 women were controls. Three kinds of cervical images were acquired from colposcopy including the saline image of cervix after saline irrigation, the acetic acid image of cervix after applying acetic acid solution, and the iodine image of cervix after applying Lugol's iodine solution. Each kind of image was used to build a single-image based deep learning model by the VGG-16 convolutional neural network, respectively. A multiple-images based deep learning model was built using multivariable logistic regression (MLR) by combining the single-image based models. The performance of the visual inspection was also obtained. The results of the cytology test and HPV test were used to build a Cytology-HPV joint diagnostic model by MLR. Finally, a cross-modal integrated model was built using MLR by combining the multiple-images based deep learning model, the cytology test results, and the HPV test results. The performances of models were tested in an independent test set using the area under the receiver operating characteristic curve (AUC). RESULTS: The saline image, acetic acid image, and iodine image based deep learning models had AUC of 0.760, 0.791, and 0.840. The multiple-images based deep learning model achieved an improved AUC of 0.845. The AUC of the visual inspection was 0.751. The Cytology-HPV joint diagnostic model had an AUC of 0.837, which was higher than the cytology test (AUC = 0.749) and the HPV test (AUC = 0.742). The cross-modal integrated model achieved the best performance with AUC of 0.921. CONCLUSIONS: Combining all kinds of cervical images were benefit for improving the performance of the colposcopy based deep learning model, and more accurate cervical screening could be achieved by incorporating the colposcopy based deep learning model, the cytology test results, and the HPV test results.

Lack of Association Between Helicobacter pylori Infection and the Risk of Thyroid Nodule Types: A Multicenter Case-Control Study in China.

The prevalence of Helicobacter pylori infection is high worldwide, while numerous research has focused on unraveling the relationship between H. pylori infection and extragastric diseases. Although H. pylori infection has been associated with thyroid diseases, including thyroid nodule (TN), the relationship has mainly focused on potential physiological mechanisms and has not been validated by large population epidemiological investigations. Therefore, we thus designed a case-control study comprising participants who received regular health examination between 2017 and 2019. The cases and controls were diagnosed via ultrasound, while TN types were classified according to the guidelines of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Moreover, H. pylori infection was determined by C14 urea breath test, while its relationship with TN type risk and severity was analyzed using binary and ordinal logistic regression analyses. A total of 43,411 participants, including 13,036 TN patients and 30,375 controls, were finally recruited in the study. The crude odds ratio (OR) was 1.07 in Model 1 (95% CI = 1.03-1.14) without adjustment compared to the H. pylori non-infection group. However, it was negative in Model 2 (OR = 1.02, 95% CI = 0.97-1.06) after being adjusted for gender, age, body mass index (BMI), and blood pressure and in Model 3 (OR = 1.01, 95% CI = 0.97-1.06) after being adjusted for total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein on the basis of Model 2. Control variables, including gender, age, BMI, and diastolic pressure, were significantly correlated with the risk of TN types. Additionally, ordinal logistic regression results revealed that H. pylori infection was positively correlated with malignant differentiation of TN (Model 1: OR = 1.06, 95% CI = 1.02-1.11), while Model 2 and Model 3 showed negative results (Model 2: OR = 1.01, 95% CI = 0.96-1.06; Model 3: OR = 1.01, 95% CI = 0.96-1.05). In conclusion, H. pylori infection was not significantly associated with both TN type risk and severity of its malignant differentiation. These findings provide relevant insights for correcting possible misconceptions regarding TN type pathogenesis and will help guide optimization of therapeutic strategies for thyroid diseases.

Ureteroscopic holmium laser to transect the greater omentum to remove an abdominal drain: Four case reports.

BACKGROUND: Drainage tube removal is difficult when the greater omentum becomes incarcerated in the drainage tube through the side holes. Currently, known removal methods are either ineffective or will cause additional damage to the patient in a secondary operation. Ureteroscopy and the holmium laser have been used in various surgical techniques in urology, and in theory, they are expected to be a good strategy for solving the problem of tissue incarceration. CASE SUMMARY: Four patients diagnosed with difficult removal of an abdominal drainage tube following abdominal surgery are reported. All patients underwent surgery to remove the incarcerated greater omentum in the drainage tube using a holmium laser and a ureteroscope, and a new 16-F drain was then placed in the abdominal or pelvic cavity. The efficacy of this technique was evaluated by intraoperative conditions, success rate, and operating time; safety was evaluated by perioperative conditions and the probability of postoperative complications. All four operations went smoothly, and the drains were successfully removed in all patients. The average operating time was 24.5 min. Intraoperatively, the average irrigation volume was 892.0 mL, the average drainage volume was 638.5 mL, and no bleeding or damage to surrounding tissues was observed. Postoperatively, the average drainage volume was 32.8 mL and the new drains were removed within 36 h. All patients were able to get out of bed and move around within 12 h. Their visual analogue pain scores were all below 3. The average follow-up duration was 12.5 mo and no complications such as fever or bleeding were noted. CONCLUSION: Ureteroscopic holmium laser surgery is an effective, safe and minimally invasive technique for removing drains where the greater omentum is incarcerated in the abdominal drain.

Design and Fabrication of a Microfluidic Chip for Particle Size-Exclusion and Enrichment.

Based on the size of particles, a microfluidic chip integrating micro particles capture, controlled release and counting analysis was designed and fabricated in this paper. The chip is composed of a polydimethylsiloxane (PDMS) cover sheet and a PDMS substrate. The PDMS substrate is made of a sample inlet, microfluidic channels, a micropillar array, a three-dimensional (3D) focusing channel, and a sample outlet. The chip was fabricated by the multistep SU-8 lithography and PDMS molding method in this study. The micropillar array and channels in the chip can be molded in one step and can be replicated multiple times, which reduces the production cost and increases the practicability of the chip. Using a homemade electromagnetic drive device, the detection function of the chip was tested using a deionized water solution containing 22 µm polyethylene particles. The results showed that under the action of electromagnetic force, the chip enriched polyethylene particles; when the electromagnetic force disappeared, the enriched polyethylene particles were released by injecting buffer solution, and it was looked at as new sample solution. The flow rate of the sample solution and the sheath flow solution (deionized water) was injected into the three-dimensional focusing channel at a flow rate ratio of 1:4, and the polyethylene particles sample solution was focused, which could be used for the counting and analysis of polyethylene particles. The work of this paper can provide a reference for the subsequent detection of circulating tumor cells (CTCs).

Sublethal hyperthermia enhances anticancer activity of doxorubicin in chronically hypoxic HepG2 cells through ROS-dependent mechanism.

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism.

Predictive Factors for Live Birth in Fresh In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment in Poor Ovarian Reserve Patients Classified by the POSEIDON Criteria.

The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into "expected" or "unexpected" groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m2, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.

The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.

OBJECTIVES: Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. MATERIALS AND METHODS: Bone structure and histological changes in Trpv6 knockout mice were examined using micro-computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC-STAMP, Atp6v0d2 and TRAP, was measured by qRT-PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF-PI3K-AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. RESULTS: We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF-PI3K-AKT signalling pathway. Blocking of the IGF-PI3K-AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. CONCLUSIONS: Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.

MicroRNA-135a-induced formation of CD133+ subpopulation with cancer stem cell properties in cervical cancer.

Cancer stem cells (CSCs) play significant roles in tumor initiation. MicroRNA-135a (miR-135a) induced the formation of a CD133+ subpopulation from a human papillomavirus-immortalized cervical epithelial cell line. Compared with the CD133- cells, the CD133+ cells expressed higher levels of miR-135a and OCT4, exhibited significantly higher tumorsphere forming capacity and the time required for tumorsphere formation was shortened in the second generation. Serum induction suppressed the expression of CD133, OCT4 and miR-135a, but increased expression of involucrin in the miR-135a-induced CD133+ cells. The miR-135a-induced CD133+ cells were tumorigenic in a limiting dilution approach in vivo. The cells expressed significantly higher level of active ß-catenin and OCT4 than the CD133- counterpart. Wnt3a enhanced the expression of OCT4 and CD133 in cervical cancer cells but failed to enhance CD133 transcription in normal cervical cells. Wnt3a stimulation also increased tumorsphere size and self-renewal of miR-135a-induced CD133+ subpopulation. Wnt/ß-catenin inhibition suppressed tumorsphere formation while Wnt3a partially nullified the inhibitory effect. Taken together, miR-135a induced the formation of a subpopulation of cells with CSC properties both in vitro and in vivo and the Wnt/ß-catenin signaling pathway is essential to maintain its tumorigenicity.