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Shih-Lung Cheng,1,2 Ping-Huai Wang,1 Cheng-Yu Chang,1 Hsu-Hui Wang,1 Chung-Jen Wang,1 Kuan-Ming Chiu2,3 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan; 2The Graduate Institute of Medicine, Yuan-Ze University, Taoyuan City, Taiwan; 3Division of Cardiovascular Surgery, Far Eastern Memorial Hospital, New Taipei City, 220, TaiwanCorrespondence: Kuan-Ming Chiu, Division of Cardiovascular Surgery, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya S. Road, Banqiao District, New Taipei City, 220, Taiwan, Tel +886-2-89667000, Email kmchius@gmail.comBackground: Molnupiravir (MOL) is an oral antiviral medication that has recently been treated for COVID-19.Objectively: We perform a prospective and observational study to elucidate the efficacy and safety of MOL in healthcare patients with COVID-19.Materials and Methods: A observational, non-randomized study of patients diagnosed with COVID-19 in 46 healthcare facilities and treated with MOL started within 5 days after the onset of signs or symptoms. We recorded data for all patients, including demographic data, clinical features, and symptoms. Treatment response was classified into cure, stable, hospitalization and death. Multivariate analysis was performed with stepwise logistic regression for hospitalization and death risk factors.Results: In total, 856 patients were diagnosed as having COVID-19 and treated with MOL during the study period. Of those, 496 patients (57.9%) were cured, 256 patients (29.9%) in stable condition, 104 patients (12.2%) hospitalized, and 22 patients (2.6%) died, respectively. There was significant effectiveness (87.8%) in COVID-19 patients using MOL. Multivariate analysis was performed to confirm the risk factors for hospitalization and death and included elder age (> 80 years old) (odds ratio (OR) 2.2, 95% confidence interval (CI): 1.1– 6.9), old cerebrovascular accident (CVA) (OR=4.1, 95% CI: 1.3– 9.9), the presence of diabetes mellitus (DM) (OR=2.6, 95% CI: 1.2– 9.1) and chronic respiratory diseases (OR=2.4, 95% (CI): 1.3– 8.1).Limitations: This is an observational study, neither randomized study nor control group study.Conclusion: Initial treatment with MOL has the treatment benefits and is well tolerated for patients with COVID-19 in healthcare facilities. Older age, old CVA, DM, and chronic respiratory diseases were independent risk factors for hospitalization and mortality. The results demonstrate there are important clinical benefits of MOL beyond the reduction in hospitalization or death for these patients with more comorbidities in Taiwan.Keywords: molnupiravir, COVID-19, healthcare facility, clinical benefit, hospitalization, comorbidity

Chen-Yu Huang,1,2 Wen-Hsun Chang,3,4 Hsin-Yi Huang,5 Chao-Yu Guo,4,6 Yiing-Jenq Chou,4,6 Nicole Huang,4,6 Wen-Ling Lee,2,7,8 Peng-Hui Wang1,2,9,10 1Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 5Biostatics Task Force, Taipei Veterans General Hospital, Taipei, Taiwan; 6Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; 7Department of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 8Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan; 9Female Cancer Foundation, Taipei, Taiwan; 10Department of Medical Research, China Medical University Hospital, Taichung, TaiwanCorrespondence: Wen-Ling LeeDepartment of Medicine, Cheng-Hsin General Hospital, 45, Cheng-Hsin Street, Taipei, TaiwanEmail johnweiwang@gmail.comPeng-Hui WangDepartment of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, 201, Section 2, Shih-Pai Road, Taipei 112, TaiwanFax +886-2-55702788Email pongpongwang@gmail.comPurpose: The goal of the current study is to determine the risk of subsequent development of epithelial ovarian cancer (EOC) in women after ovarian surgery for benign ovarian tumors.Patients and Methods: We conducted the nationwide population-based historic cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan. Eleven thousand six hundred twenty women who underwent ovarian surgery for ovarian benign diseases were analyzed. The collected data included age, types of ovarian surgery, medical history by Charlson comorbidity index (CCI), infertility (yes/no), pelvic inflammatory disease (PID) (yes/no), tubal ligation (yes/no), total/subtotal hysterectomy (TH/STH) (yes/no), and endometrioma (yes/no). We used the Kaplan–Meier method and the Log-rank test to evaluate the risk factors. Cox proportional hazard methods were used to evaluate risk factors for the subsequent development of EOC. Multivariate analysis using Cox stepwise forward regression was conducted for the covariate selected in univariate analysis. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Wald test.Results: Subsequent EOC incidence rate (IR, incidence per 10,000 person-years) of women after ovarian surgery for benign ovarian tumors was 2.98. Separating into four groups based on different age, IR of EOC was 1.57 (< 30 years), 4.71 (30– 39 years), 3.59 (40– 49 years) and 0.94 (≥ 50 years), respectively. Univariate and multivariate analyses identified only high level of CCI (≥ 2 or more) as an independent risk factor for subsequent development of EOC in women after ovarian surgery for benign ovarian tumors (HR 59.17, 95% CI 7.50– 466.80 in women with CCI level of 2 and HR 190.68, 95% CI 24.33– 2494.19, in women with CCI level ≥ 3, respectively).Conclusion: Our results, if confirmed, suggest that women with other comorbidities (CCI) should be well informed that they may have a higher risk of subsequent development of EOC when ovarian surgery is planned even though the final pathology showed a benign ovarian tumor.Keywords: benign ovarian tumor, cohort study, epidemiology, epithelial ovarian cancer, ovarian surgery, risk

Ping-Hui Wang,1 Chia-Lung Li,2,3 Chung-Jung Shao,4 Kuo-Chen Wu,5 Tai-Chang Chern,6 I-Ming Jou7,81Department of Orthopedics, Chi-Mei Medical Center, Tainan 710, Taiwan; 2Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 3Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; 4Department of Orthopedics, Tainan Municipal Hospital, Tainan 709, Taiwan; 5Department of Orthopedics, Kuo General Hospital, Tainan, Taiwan; 6Chern Tai-Chang Orthopedic Clinic, Pingtung 900, Taiwan; 7Department of Orthopedics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; 8Department of Orthopedics, National Cheng Kung University, Tainan, TaiwanPurpose: The purpose of the current study was to evaluate the effectiveness of ultrasound-guided percutaneous carpal tunnel release in hemodialysis patients with carpal tunnel syndrome.Methods: From February 2009 to April 2013, a prospective review of 113 consecutive cases of ultrasound-guided percutaneous carpal tunnel release was carried out in 84 hemodialysis patients. Results were analyzed by clinical subjective scale, two self-administered questionnaires, and functional evaluations at seven time points (1 week and 1, 3, 6, 12, 18, and 24 months).Results: Satisfactory symptom improvement in patients was 82%, 80%, 86%, 89%, 90%, 91%, and 90% at 1 week and 1, 3, 6, 12, 18, and 24 months postoperatively, respectively. Moderate pain was suffered in 11.5% of patients within 1 week, 8.8% within 1 month, 2.7% within 3 months, and none after 12 months postoperatively. Static two-point discrimination and Semmes–Weinstein monofilament examinations presented significant improvements after 1 week and 1 month postoperatively and with time. Postoperative grip power demonstrated recovery and a significant increase after 3 and 6 months postoperatively. Three-jaw chuck-pinch strength showed significant increase after 1 month postoperatively. There were no operative complications.Conclusion: Ultrasound-guided percutaneous carpal tunnel release is an effective and safe procedure in hemodialysis patients with carpal tunnel syndrome. The advantages include a less invasive procedure, no tourniquet needed, only limited infiltration anesthesia, minimal soft-tissue exploration, and relatively short operation time. Our data suggest this technique can reliably relieve clinical symptoms, with early restoration of grip and pinch strength.Keywords: carpal tunnel, hemodialysis, ultrasound, percutaneous release

Ing-Luen Shyu,1,2 Li-Yu Hu,3 Yi-Jen Chen,1,4,5 Peng-Hui Wang,1,4,5 Ben-Shian Huang1,4,5 1Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Obstetrics and Gynecology, Chi-Mei Hospital, Tainan City, Taiwan; 3Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Obstetrics and Gynecology, School of Medicine, Taipei, Taiwan; 5Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Introduction: Depression might affect women with cervical cancer and can deteriorate their quality of life or even their compliance with cancer treatments. The aim of this study was to investigate the incidence of depression and risk factors for developing depression among women with cervical cancer in Taiwan. Patients and methods: This study enrolled patients with newly diagnosed cervical cancer from the National Health Insurance Research Database in Taiwan. From a population of 21,400,826 residents, each cervical cancer patient was matched with one subject without cervical cancer according to sex, age, and comorbidities with the same diagnostic index. The International Classification of Diseases, Ninth Revision, code 180.9 was used to identify patients with cervical cancer, and 296.0X–296.1X, 296.4X–296.8X, 296.2X–296.3X, 300.4, and 311.X codes were used to identify those with depressive disorders.Results: In total, 19,316 newly diagnosed cervical cancer patients were enrolled from January 2000 to December 2005, and the median follow-up period was 5.23 years (1.75–8.48 years). The prevalence of depressive disorder was 4.21% (813 of 19,316) in the cervical cancer cohort, and it was 3.85% (744 of 19,316) in the control cohort. The incidence risk ratio of depressive disorders was 1.35 (95% CI =1.22–1.49, P

Ping-Hui Wang,1 Cheng-Chang Yang,2 Wei-Ren Su,3 Po-Ting Wu,3 Shun-Chien Cheng,1 I-Ming Jou4 1Department of Orthopedics, Chi-Mei Medical Center, 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 3Department of Orthopedics, National Cheng Kung University Hospital, Tainan, 4Department of Orthopedics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Purpose: To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods: Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results: Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion: Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy. Keywords: compression, decompression, streptozotocin, sciatic nerve, diabetes, rat

Background and aimMitochondrial dysfunction contributes to the pathophysiology of diabetic cardiomyopathy. The aim of this study was to investigate the acute changes in the mitochondrial proteome in response to insulin stimulation.Methods and resultsCardiac mitochondria from C57BL/6 mice after insulin stimulation were analyzed using two-dimensional fluorescence difference gel electrophoresis. MALDI-TOF MS/MS was utilized to identify differences. Two enzymes involved in metabolism and four structural proteins were identified. Succinyl-CoA ligase [ADP forming] subunit beta was identified as one of the differentially regulated proteins. Upon insulin stimulation, a relatively more acidic isoform of this protein was increased by 53% and its functional activity was decreased by ∼32%.ConclusionsThis proteomic remodeling in response to insulin stimulation may play an important role in the normal and diabetic heart.

Objective: To compare the immediate results of patients undergoing either two-channel single-port laparoscopic-assisted vaginal hysterectomy or conventional multiport laparoscopic-assisted vaginal hysterectomy.Methods: Patients were randomly assigned to undergo laparoscopic-assisted vaginal hysterectomy using the single-port (n=50) or conventional (n=50) approach. The outcome measures included blood loss, operative time, intraoperative and immediate postoperative complications, time to flatus passage after operation, and postoperative pain (assessed by the visual analog scale score and postoperative analgesics use).Results: The general characteristics of the patients were similar in both groups. There were no statistically significant differences in operative time, estimated blood loss, time to first flatus, intraoperative and immediate postoperative complications, shoulder tip pain, or length of hospital stay between the two groups. However, postoperative pain was significantly less in the single-port group compared with the conventional group, as evidenced by lower mean scores on the visual analog scale (3.64±2.75 compared with 5.08±2.76 at 24 hours, P=.011 and 1.94±2.31 compared with 2.84±2.07 at 48 hours, P=.043) and less mean accumulated dose of postoperative analgesics (74.40±24.25 mg compared with 104.80±57.08 mg of meperidine, P=.001; 16±13.40 mg compared with 33.6±28.7 mg of tenoxicam, P<.001).Conclusion: Transumbilical two-channel single-port laparoscopic-assisted vaginal hysterectomy significantly decreases postoperative pain and analgesic use.Clinical Trial Registration: Clinical Trials.gov, www.clinicaltrials.gov, NCT01048931.Level Of Evidence: I. [ABSTRACT FROM AUTHOR]

Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC(50) value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC. [ABSTRACT FROM AUTHOR]

Background: Dietary protein has long been thought to play a role in the progression of chronic renal disease, but clinical trials to date have not consistently shown that dietary protein restriction is beneficial.Purpose: To use meta-analysis to assess the efficacy of dietary protein restriction in previously published studies of diabetic and nondiabetic renal diseases, including the recently completed Modification of Diet in Renal Disease Study.Data Sources: The English-language medical literature published from January 1966 through December 1994 was searched for studies examining the effect of low-protein diets in humans with chronic renal disease. A total of 1413 patients in five studies on nondiabetic renal disease (mean length of follow-up, 18 to 36 months) and 108 patients in five studies of type I diabetes mellitus (mean length of follow-up, 9 to 35 months) were included.Study Selection: Randomized, controlled studies were selected for nondiabetic renal disease; randomized, controlled studies or time-controlled studies with nonrandomized crossover design were selected for diabetic nephropathy.Data Extraction: Data in tables, figures, or text were independently extracted by two of the authors.Data Synthesis: The relative risk for progression of renal disease in patients receiving a low-protein diet compared with patients receiving a usual-protein diet was calculated by using a random-effects model. In five studies of nondiabetic renal disease, a low-protein diet significantly reduced the risk for renal failure or death (relative risk, 0.67 [95% Cl, 0.50 to 0.89]). In five studies of insulin-dependent diabetes mellitus, a low-protein diet significantly slowed the increase in urinary albumin level or the decline in glomerular filtration rate or creatinine clearance (relative risk, 0.56 [Cl, 0.40 to 0.77]). Tests for heterogeneity showed no significant differences in relative risk among studies of either diabetic or nondiabetic renal disease. No significant differences were seen between diet groups in pooled mean arterial blood pressure (diabetic and nondiabetic patients) or glycosylated hemoglobin level (diabetic patients only).Conclusion: Dietary protein restriction effectively slows the progression of both diabetic and nondiabetic renal diseases. [ABSTRACT FROM AUTHOR]

In this study, green tea waste (GTW) was used to synthesize the iron oxide (IO) nanoparticles (IO@GTW) to facilitate the adsorption of heavy metals from wastewaters. To satisfy structural integrity needs, the synthesized IO@GTW was incorporated into a polyvinyl alcohol (PVA)/alginate polymer network to obtain PVA/alginate/IO (PAI) hydrogels. Experimental techniques of transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR) were subsequently used to confirm the successful synthesis of IO nanoparticles. Scanning electron microscopy (SEM) established the porous microstructure of PAI hydrogels, while FT-IR analysis revealed the physical incorporation of IO@GTW in PAI hydrogels. The adsorption of Cu2+ and Cr6+ on PAI hydrogels was subsequently investigated. The present study was able to show that the removal ratio and adsorption capacity of the synthesized PAI hydrogels depended on the pH, initial concentration of metal ions in the solution, and contact time. The equilibrium isotherms of Cu2+ and Cr6+ adsorption were well-described using Langmuir and Freundlich isotherm models. The adsorption kinetics of Cu2+ can be modelled using the pseudo-second-order model, and the adsorption kinetics of Cr6+ can be modelled using both pseudo-first-order and intraparticle diffusion models. This study, therefore, demonstrates the functionality of integrating green tea waste in a polymeric composite to perform as an effective and green adsorbent for heavy metal removal, thus indicating the viability of its future application in wastewater treatment operations.

Rabies is a zoonotic infectious disease that targets the nervous system of human and animals and has about 100% fatality rate without treatment. Rabies virus is a bullet-like viral particle composed of five structural proteins, including nucleoprotein (N), phosphorylated protein (P), matrix protein (M), glycoprotein (G), and large subunit (L) of RNA-dependent RNA polymerase. These multifunctional viral proteins also play critical roles in the immune escape by inhibiting specific immune responses in the host, resulting in massive replication of the virus in the nervous system and abnormal behaviors of patients such as brain dysfunction and hydrophobia, which ultimately lead to the death of patients. Herein, the role of five structural proteins of rabies virus in the viral replication and immune escape and its implication for the development of vaccines were systemically reviewed, so as to shed light on the understanding of pathogenic mechanism of rabies virus., Competing Interests: The authors declare there are no competing interests.

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae&#95;UCG&#95;001 . Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale.

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates ( p < 0.01), and feed conversion ratios ( p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics ( p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment ( p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics ( p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets ( p < 0.05), while antibiotic treatment reduced beneficial bacteria ( p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets.

Background: Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer., Objectives: To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients., Search Strategy: In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022., Selection Criteria: Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients., Data Collection and Analysis: Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I 2 ) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias., Main Results: Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively)., Conclusions: The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Competing Interests: Conflicts of interest: Dr. Peng-Hui Wang, an editorial board member at the Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. Wen-Hsun Chang declares that he has no conflicts of interest related to the subject matter or materials discussed in this article.

Competing Interests: Conflicts of interest: Dr. Peng-Hui Wang, an editorial board member at the Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. Chia-Hao Liu declares that he has no conflicts of interest related to the subject matter or materials discussed in this article.

The relationship between metastasis-associated protein 2 (MTA2) overexpression and tumor growth and metastasis has been extensively studied in a variety of tumor cells but not in human osteosarcoma cells. This study aims to elucidate the clinical significance, underlying molecular mechanisms, and biological functions of MTA2 in human osteosarcoma in vitro and in vivo . Our results show that MTA2 was elevated in osteosarcoma cell lines and osteosarcoma tissues and was associated with tumor stage and overall survival of osteosarcoma patients. Knockdown of MTA2 inhibited osteosarcoma cell migration and invasion by reducing the expression of urokinase-type plasminogen activator (uPA). Bioinformatic analysis demonstrated that high levels of uPA in human osteosarcoma tissues correlated positively with MTA2 expression. Furthermore, treatment with recombinant human uPA (Rh-uPA) caused significant restoration of OS cell migration and invasion in MTA2 knockdown osteosarcoma cells. We found that ERK1/2 depletion increased the expression of uPA, facilitating osteosarcoma cell migration and invasion. Finally, MTA2 depletion significantly reduced tumor metastasis and the formation of lung nodules in vivo . Overall, our study suggests that MTA2 knockdown suppresses osteosarcoma cell metastasis by decreasing uPA expression via ERK signaling. This finding provides new insight into potential treatment strategies against osteosarcoma metastasis by targeting MTA2.

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m 2 +triweekly cisplatin 40 mg/m 2 ), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m 2 ) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC., Competing Interests: Declaration of competing interest Dr. Peng-Hui Wang and Dr. Szu-Ting Yang, editorial board members at Taiwanese Journal of Obstetrics and Gynecology, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024. Published by Elsevier B.V.)

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls <15 years of age; (2) a high-performance screening procedure to 70% of women during the reproductive age (at the age of 35 and 45 years of age); and (3) an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Among the aforementioned three pillars, a full HPV vaccination has been introduced in our previous review, of which we have discussed the policy and strategy of HPV vaccination in the world and also reviewed the efficacy of HPV vaccination, with a successful reduction of over 90% of HPV-associated neoplasms. The aims of the current review will target another pillar-an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Since the early-stage cervical cancer has a favorable outcome and the treatment recommendation has been established, therefore, the current review focuses on women with persistent, recurrent and metastatic cervical cancers (advanced cervical cancers), which are still a biggest challenge based on its extremely worse outcomes before the introduction of immune checkpoint inhibitors (ICIs). Integration of ICIs into conventional chemotherapy (paclitaxel-cisplatin) has become the new standard therapy for those patients with advanced cervical cancers. The recent clinical trials, such as KENOTE 826 and KENOTE A18 showing a dramatical improvement of both progression free survival and overall survival have approved the therapeutic efficacy of this combination as ICI plus paclitaxel-platinum (cisplatin or carboplatin) with/without bevacizumab to women with persistent, recurrent and metastatic cervical cancers., Competing Interests: Declaration of competing interest Dr. Peng-Hui Wang and Dr. Szu-Ting Yang, editorial board members at Taiwanese Journal of Obstetrics and Gynecology, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024. Published by Elsevier B.V.)

Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose-dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases cleavage. Taken together, our results demonstrate that DSK has anti-cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38-mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management., (© 2024 Wiley Periodicals LLC.)

Objective: The endometrial cancer is a disorder with elevated oxidative stress. The high oxidative stress resulting from hyperglycemia can lead to diabetic retinopathy (DR) development which is a complication of type 2 diabetes mellitus. Accordingly, we aim to evaluate the potential relationship between the endometrial cancer and following DR development., Methods: A retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. Individuals diagnosed with endometrial cancer were matched to the non-endometrial cancer patients in a 1:4 ratio. The major outcomes are the presence of DR, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) according to diagnostic codes. Cox proportional hazard regression was used to show the adjusted hazard ratio (aHR) with 95% confidence interval (CI) of major outcomes between groups., Results: There were 99 (2.3%), 20 (0.5%), and 14 (0.3%) cases with DR, DME and PDR in the endometrial cancer group, respectively. Another 303 (1.8%), 35 (0.2%), and 27 (0.2%) with DR, DME and PDR were observed in the control group, respectively. The endometrial cancer group revealed a significantly higher incidence of DR compared with the control group (aHR 1.51, 95% CI 1.20-1.90, P < 0.001). The cumulative probability of DR was also higher in the endometrial cancer group than in the control group (P < 0.001). The relationship between endometrial cancer and DR was significantly higher in patients aged over 70 years (P = 0.008). In addition, a higher incidence of DR was found during the first 5 years after the endometrial cancer diagnosis (P < 0.001)., Conclusions: The endometrial cancer correlates to a higher incidence of subsequent DR, especially within first 5 years of endometrial cancer diagnosis., (© 2024 International Federation of Gynecology and Obstetrics.)