First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial.

BACKGROUND: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear. METHODS: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety. FINDINGS: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively. CONCLUSIONS: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC. FUNDING: This work was funded by Shanghai Henlius Biotech, Inc.

The effects of the predictability of acclimatory temperature on the growth and thermal tolerance of juvenile Spinibarbus sinensis.

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

The effect of liver metastases on clinical efficacy of first-line programmed death-1 inhibitor plus chemotherapy in esophageal squamous cell carcinoma: A post hoc analysis of ASTRUM-007 and meta-analysis.

OBJECTIVE: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. METHODS: A post hoc exploratory analysis of ASTRUM-007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. RESULTS: The post hoc analysis of ASTRUM-007 showed that although patients with liver metastases had a worse prognosis comparing with the non-liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15-2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09-1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01-2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84-2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37-0.97; HR of OS: 0.68; 95% CI, 0.43-1.11) and the non-liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49-0.80; HR of OS: 0.69; 95% CI, 0.55-0.87) with similar magnitude. Three randomized controlled trials were included in the meta-analysis. Pooled HRs demonstrated that the addition of anti-PD-1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. CONCLUSIONS: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD-1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

Migrating foreign bodies of penis: a case report and literature review.

BACKGROUND: Only a few cases have been reported about active foreign body implantation in the cavernous body of the penis. CASE PRESENTATION: A 47-year-old man inserted two needles from the glans penis into the bilateral penile sponge body. Subsequently, two needles migrated through the penile cavernous body into the pelvic cavity. Attempts to remove the needles through the penis were unsuccessful. Eventually, after a duration exceeding one month, the displaced needles were removed in stages from the buttocks. CONCLUSION: A few cases of intracavernosal-injection-therapy-associated needle breakage and retention have been reported globally. And this is the first case in China documenting the migration of foreign bodies within the penile region. In this condition, it is of utmost importance to engage the expertise of experienced andrologists to minimize the risk of excessive manipulation, thereby ensuring that inadvertent deep penetration of the needle into the penile tissue is prevented. In case the foreign body has migrated deeper into the tissues and the patient does not exhibit any specific symptoms or risks of macrovascular injury-related bleeding, close surveillance of its movement can be implemented. Surgical intervention can be initiated once the foreign body has reached a suitable position. Moreover, a psychiatric evaluation should be recommended for patient to discover any underlying mental health disorders.

RéSUMé: CONTEXTE: Seuls quelques cas ont été rapportés concernant l'implantation active d'un corps étranger dans le corps caverneux du pénis. PRéSENTATION DU CAS: Un homme de 47 ans a inséré deux aiguilles, par le gland du pénis, dans les corps spongieux du pénis. Par la suite, les deux aiguilles ont migré à travers le corps caverneux du pénis jusque dans la cavité pelvienne. Les tentatives pour retirer les aiguilles à travers le pénis ont été infructueuses. Finalement, après une durée de plus d'un mois, les aiguilles déplacées ont été retirées, par étapes, au niveau des fesses. CONCLUSION: Quelques cas de rupture et de rétention d'aiguille associés au traitement par injection intracaverneuse ont été signalés dans le monde. Il s'agit ici du premier cas en Chine qui documente la migration de corps étrangers dans la région du pénis. Dans cette situation, il est de la plus haute importance de faire appel à l'expertise d'andrologues expérimentés pour minimiser le risque de manipulation excessive, garantissant ainsi que la pénétration profonde par inadvertance de l'aiguille dans le tissu pénien est prévenue. Dans le cas où le corps étranger a migré plus profondément dans les tissus et que le patient ne présente pas de symptômes spécifiques ou de risques de saignements liés à une lésion macrovasculaire, une surveillance étroite du mouvement du corps étranger peut être mise en œuvre. L'intervention chirurgicale peut être initiée une fois que le corps étranger a atteint une position appropriée. Enfin, une évaluation psychiatrique devrait être recommandée à la recherche de tout trouble sous-jacent de santé mentale.

Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

Focus on Upper Urinary Tract Stones Combined with Parenchymal Infiltrative Renal Pelvis Cancer.

INTRODUCTION: Upper urinary tract stones combined with parenchymal infiltrative renal pelvic cancer are challenging to detect on imaging and to evaluate the differential diagnosis. CASE PRESENTATION: The symptoms and diagnoses in three cases of parenchymal infiltrative renal pelvic cancer and upper urinary tract stones that occurred between June 2019 and June 2022 were reviewed. Primary symptoms of lumbar discomfort and hematuria were evident in all 3 patients. Preoperative computed tomography (CT) abdominal imaging revealed that all three cases had hydronephrosis along with renal stones, while the other two cases only had localized hypoenhancement of the renal parenchyma, which was only thought to be limited inflammatory changes in the renal cortex as a result of the combination of renal pelvis infection. After percutaneous nephrolithotomy or ureteroscopic lithotripsy, a combined renal pelvis tumor was discovered in all of these instances. Radical tumor surgery was later performed. One patient who had several tumor metastases passed away 6 months after surgery. A case with multiple metastases was discovered 15 months after surgery and survived with the help of the current chemotherapy. A case with a bladder tumor recurrence was discovered 16 months after surgery and had transurethral bladder tumor electrosurgery and routine bladder perfusion chemotherapy. CONCLUSION: Upper urinary tract stones and parenchymal infiltrative pyel carcinoma have atypical imaging, easily confused with infectious diseases. CT or computed tomography urography (CTU) must be considered by urologists. Patients who have a CT with local renal parenchyma density should be suspected of having parenchymal invasive renal pelvis carcinoma; a needle biopsy ought to be performed; and repeat biopsies may be performed if necessary. High-risk individuals need multiple, sufficient biopsies as needed and a comprehensive intraoperative assessment of the renal pelvic mucosa.

Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1ß. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.

Femoral Tunnel Malposition, Increased Lateral Tibial Slope, and Decreased Notch Width Index Are Risk Factors for Non-Traumatic Anterior Cruciate Ligament Reconstruction Failure.

PURPOSE: To identify risk factors for patients who sustain nontraumatic anterior cruciate ligament reconstruction (ACLR) failure. METHODS: A retrospective analysis was performed on patients undergoing primary or revision ACLR in our institution between 2010 and 2018. Patients sustaining insidious-onset knee instability without history of trauma were identified as nontraumatic ACLR failure and assigned to the study group. The control group of subjects who showed no evidence of ACLR failure with minimum 48-month follow-up were matched in a 1:1 ratio based on age, sex, and body mass index. Anatomic parameters including tibial slope (lateral [LTS], medial [MTS]); tibial plateau subluxation (lateral [LTPsublx], medial [MTPsublx]); notch width index (NWI); and lateral femoral condyle ratio were measured with magnetic resonance imaging or radiography. Graft tunnel position was assessed using 3-dimensional computed tomography and reported in 4 dimensions: deep-shallow ratio (DS ratio) and high-low ratio for femoral tunnel, anterior-posterior ratio and medial-lateral ratio for tibial tunnel. Interobserver and intraobserver reliability were evaluated by the intraclass correlation coefficient (ICC). Patients' demographic data, surgical factors, anatomic parameters, and tunnel placements were compared between the groups. Multivariate logistic regression and receiver operating characteristic curve analysis was used to discriminate and assess the identified risk factors. RESULTS: A total of 52 patients who sustained nontraumatic ACLR failure were included and matched with 52 control subjects. Compared to patients with intact ACLR, those who sustained nontraumatic ACLR failure showed significantly increased LTS, LTPsublx, MTS, and deceased NWI (all P < .001). Moreover, the average tunnel position in the study group was significantly more anterior (P < .001) and superior (P = .014) at the femoral side and more lateral (P = .002) at the tibial side. Multivariate regression analysis identified LTS (odds ratio [OR] = 1.313; P = .028), DS ratio (OR = 1.091; P = .002), and NWI (OR = 0.813; P = .040) as independent predictors of nontraumatic ACLR failure. LTS appeared to be the best independent predictive factor (area under the curve [AUC] = 0.804; 95% confidence interval [CI], 0.721-0.887), followed by DS ratio (AUC = 0.803; 95% CI, 0.717-0.890), and NWI (AUC = 0.756; 95% CI, 0.664-0.847). The optimal cutoff values were 6.7° for increased LTS (sensitivity = 0.615, specificity = 0.923); 37.4% for increased DS ratio (sensitivity = 0.673, specificity = 0.885); and 26.4% for decreased NWI (sensitivity = 0.827, specificity = 0.596). Intraobserver and interobserver reliability was good to excellent, with ICCs ranging from 0.754 to 0.938 for all radiographical measurements. CONCLUSIONS: Increased LTS, decreased NWI, and femoral tunnel malposition are predictive risk factors for nontraumatic ACLR failure. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks.

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid ß-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Sanguinarine modulates microglial function via PPARγ activation and protects against CNS demyelination.

Microglia aggregate in regions of active inflammation and demyelination in the CNS of multiple sclerosis (MS) patients and are considered pivotal in the disease process. Targeting microglia is a promising therapeutic approach for myelin repair. Previously, we identified two candidates for microglial modulation and remyelination using a Connectivity Map (CMAP)-based screening strategy. Interestingly, with results that overlapped, sanguinarine (SAN) emerged as a potential drug candidate to modulate microglial polarization and promote remyelination. In the current study, we demonstrate the efficacy of SAN in mitigating the MS-like experimental autoimmune encephalomyelitis (EAE) in a dose-dependent manner. Meanwhile, prophylactic administration of a medium dose (2.5 mg/kg) significantly reduces disease incidence and ameliorates clinical signs in EAE mice. At the cellular level, SAN reduces the accumulation of microglia in the spinal cord. Morphological analyses and immunophenotyping reveal a less activated state of microglia following SAN administration, supported by decreased inflammatory cytokine production in the spinal cord. Mechanistically, SAN skews primary microglia towards an immunoregulatory state and mitigates proinflammatory response through PPARγ activation. This creates a favorable milieu for the differentiation of oligodendrocyte progenitor cells (OPCs) when OPCs are incubated with conditioned medium from SAN-treated microglia. We further extend our investigation into the cuprizone-induced demyelinating model, confirming that SAN treatment upregulates oligodendrocyte lineage genes and increases myelin content, further suggesting its pro-myelination effect. In conclusion, our data propose SAN as a promising candidate adding to the preclinical therapeutic arsenal for regulating microglial function and promoting myelin repair in CNS demyelinating diseases such as MS.

Computer vision-aided mmWave communications for indoor medical healthcare.

Comprehensive and exceedingly precise centralized patient monitoring has become essential to advance predictive, preventive, and efficient patient care in contemporary healthcare. Millimeter-wave (mmWave) technology, boasting high-frequency and high-speed wireless communication, holds promise as a viable solution to this challenge. This paper presents a new approach that combines mmWave communication and computer vision (CV) to achieve real-time patient monitoring and data transmission in indoor medical environments. The system comprises a transmitter, a reflective surface, and multiple communication targets, and utilizes the high-frequency, low-latency features of mmWave as well as CV-based target detection and depth estimation for precise localization and reliable data transmission. A machine learning algorithm analyses real-time images captured by an optical camera to identify target distance and direction and establish clear line-of-sight links. The system proactively adapts its transmission power and channel allocation based on the target's movements, guaranteeing complete coverage, even in potentially obstructive areas. This methodology tackles the escalating demand for high-speed, real-time data processing in modern healthcare, significantly enhancing its delivery.

Pharmacokinetic analysis of ceftazidime and cefazolin in the treatment of continuous ambulatory peritoneal dialysis-related peritonitis.

OBJECTIVE: Peritoneal dialysis-related peritonitis (PDRP) presents a significant challenge for nephrologists. Continuous intraperitoneal cefazolin and ceftazidime are recommended for the treatment of peritonitis. However, some pharmacokinetic studies have shown that doses of 15-20 mg/kg/d may not achieve sufficient therapeutic levels. In this study, we investigated the pharmacokinetics of ceftazidime and cefazolin in patients with continuous ambulatory peritoneal dialysis-related peritonitis and compared the pharmacokinetic characteristics between traditional and modified treatment groups. METHODS: From February 2017 to December 2019, 42 PDRP patients (17 males, 25 females; mean age: 50.7 ± 12.1 years; mean body weight: 60.9 ± 11.8 kg) were recruited for the study, all participants were anuric. Twenty patients were enrolled in the traditional group and treated with cefazolin (1.0 g) and ceftazidime (1.0 g) via intraperitoneal administration once daily for 14 days. Twenty-two patients were enrolled in the modified group and received the same dose of antibiotics twice daily for the initial five days, followed by once daily for the subsequent nine days. Serum and dialysate samples were collected after days 1, 2, 3, 5, 7, 10, and 14 and analyzed via liquid chromatography-mass spectrometry. RESULTS: In the traditional group, the highest and lowest serum concentrations of ceftazidime were 35.9 and 21.7 µg/mL, respectively. The highest concentration of cefazolin was 54.6 µg/mL on day 5 and the lowest concentration was 30.4 µg/mL on day 1. In the modified group, the highest and lowest serum concentrations of ceftazidime were 102.2 and 54.8 µg/mL, respectively. The highest concentration of cefazolin was 141.7 µg/mL and the lowest concentration was 79.8 µg/mL. All antibiotic concentrations were above the minimum inhibitory concentration (MIC) level (8 µg/mL of ceftazidime and 2 µg/mL of cefazolin) throughout the treatment period. However, on day 1, the concentration of ceftazidime in the third bag of dialysate effluent from the traditional group fell below the MIC level. Despite remaining above the MIC, cefazolin concentration was consistently lower in the third bag of dialysate effluent from the traditional group throughout the treatment period. CONCLUSIONS: Intraperitoneal administration of cefazolin and ceftazidime at a dose of 1 g twice daily for 5 days and then once daily for the rest of the treatment period ensured adequate therapeutic levels of antibiotics for treating anuric PDRP patients.

The prevalence rate, mortality, and 5-year overall survival of Schistosoma japonicum patients with human malignancy.

Background: Only a few studies have focused on the association between Schistosoma japonicum and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of S. japonicum patients with human malignancy. Methods: From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 S. japonicum patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The S. japonicum patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups. Results: Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between S. japonicum and non-S. japonicum patients with/without digestive system tumor (p < 0.001). The odds ratio of S. japonicum patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9). Conclusion: S. japonicum contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.

Retracted: Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Qin Zhang, Xin-wei Dong, Jia-ying Xia, Ke-ying Xu, Zhe-rong Xu. Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro. Med Sci Monit, 2017; 23: 2127-2136. DOI: 10.12659/MSM.901361.

A novel quantitative model based on gross tumor volume corresponding to anatomical distribution measured with multidetector computed tomography to determine the resectability of non­distant metastatic esophageal squamous cell carcinoma.

It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability.

Effect of quilt thermal resistance on bedding system and sleep thermal comfort.

Ambient temperature and the bedding thermal resistance are two key factors affecting sleepers' thermal comfort. Six duvets with thermal resistance of 3.81, 5.12, 6.19, 7.81, 8.75 and 8.93 clo were included to investigate the effects of duvet thermal resistance on the sleep thermal comfort zone. Six males and six females were enrolled in a whole night sleep experiment, and the ambient temperature of the sleep room was adjusted to be thermally comfortable. Skin temperature, bed climate temperature and sleep stages were all acquired. Subjective evaluations including thermal perception and sleep quality were also assessed through questionnaires. The results indicated that increasing the thermal resistance of duvets widened the thermal comfort zone of ambient temperature, with the highest thermal resistance ranging from 8.2 to 17.7 °C and the lowest from 16.4 to 22.2 °C. The upper and lower temperature limits of the comfort zone did not significantly differ in their effect on sleep quality. The recommended bed climate temperature for comfortable sleep would be in the small range of 30-33 °C, and a good quality of sleep can be guaranteed in the scenario.

Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.

Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.

2-phenylacetamide Separated from the seed of Lepidium apetalum Willd. inhibited renal fibrosis via MAPK pathway mediated RAAS and oxidative stress in SHR Rats.

BACKGROUND: Renal fibrosis with Renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress are one of the major complications in hypertension. 2-phenylacetamide (PA), a major active component of Lepidium apetalum Willd. (L.A), has numerous pharmacological effects. Its analogues have the effect of anti-renal fibrosis and alleviating renal injury. This study aims to explore the underlying mechanism of PA for regulating the renal fibrosis in SHR based on the MAPK pathway mediated RAAS and oxidative stress. METHODS: The SHR rats were used as the hypertension model, and the WKY rats were used as the control group. The blood pressure (BP), urine volume were detected every week. After PA treatment for 4 weeks, the levels of RAAS, inflammation and cytokines were measured by Enzyme-Linked Immunosorbnent Assay (ELISA). Hematoxylin-Eosin staining (HE), Masson and Immunohistochemistry (IHC) were used to observe the renal pathology, collagen deposition and fibrosis. Western blot was used to examine the MAPK pathway in renal. Finally, the SB203580 (p38 MAPK inhibitor) antagonism assay in the high NaCl-induced NRK52e cells was used, together with In-Cell Western (ICW), Flow Cytometry (FCM), High Content Screening (HCS) and ELISA to confirm the potential pharmacological mechanism. RESULTS: PA reduced the BP, RAAS, inflammation and cytokines, promoted the urine, and relieved renal pathological injury and collagen deposition, repaired renal fibrosis, decreased the expression of NADPH Oxidase 4 (NOX4), transforming growth factor-ß (TGF-ß), SMAD3 and MAPK signaling pathway in SHR rats. Meanwhile,,the role of PA could be blocked by p38 antagonist SB203580 effectively in the high NaCl-induced NRK52e cells. Moreover, molecular docking indicated that PA occupied the ligand binding sites of p38 MAPK. CONCLUSION: PA inhibited renal fibrosis via MAPK signalling pathway mediated RAAS and oxidative stress in SHR Rats.

Value of needle confocal laser microendoscopy combined with endobronchial ultrasound bronchoscopy in the diagnosis of hilar and mediastinal lymph node lesions.

Endobronchial ultrasound bronchoscopy (EBUS) and needle confocal laser endomicroscopy (nCLE) are techniques for screening benign and malignant lesions of the hilar and mediastinal lymph node (HMLN). This study investigated the diagnostic potential of EBUS, nCLE, and combined EBUS and nCLE in HMLN lesions. We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS-nCLE approach was analyzed according to the results. Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS-nCLE examination. The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively). The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11). No serious complications occurred in patients with HMLN lesions. To summarize, the diagnostic efficacy of nCLE was better than EBUS. The EBUS-nCLE combination is a suitable approach for diagnosing HMLN lesions.

Preparation of fat replacer utilizing gluten and barley ß-glucan and the interaction between them.

BACKGROUND: Fat replacers prepared from polysaccharides and proteins possess functional properties of both polysaccharides and proteins. In this study, an aqueous system of barley ß-glucan (BBG) and gluten was prepared. The interactions between BBG and gluten (with/without extrusion modification) were studied. Triple analysis methods, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and low-field nuclear magnetic resonance (LF-NMR), were utilized to analyze the freezing-thawing and thermal evaporation process, as well as the distribution state of water. Meanwhile, fluorescence microscopic analysis, dynamic rheological analysis and electrophoresis analysis were used to study the structure and rheological properties of the system. RESULTS: The results showed that BBG significantly increased the water-holding capacity of gluten, regardless of extrusion treatment, with the water absorption reaching about 4.8 to 6.4 times of its weight, which was 1 to 2.5 times higher than that without BBG. The triple analysis results suggested that BBG increased the binding capacity of the system to weakly bound water, hindered the aggregation of gluten and reduced the thermal decomposition temperature of the BBG and gluten composite system. After the gluten was extruded and homogenized with the BBG solution, the appearance of the composite system was more uniform and delicate. CONCLUSIONS: In conclusion, BBG increased the water-holding capacity of the BBG and gluten composite system. With these changes, the composite system presented great potential for the preparation of polysaccharide-gluten fat replacer. © 2023 Society of Chemical Industry.