Does the presence of blind-ended vas deferens and spermatic vessels in laparoscopic exploration of non-palpable testes conclusively indicate testicular absence?

Objective: The purpose of this study was to determine whether the presence of blind-ended vas deferens and spermatic vessels (VDSV) during laparoscopic exploration of non-palpable testes (NPT) indicates testicular absence or atrophy. Materials and methods: A retrospective analysis was conducted on clinical data of patients diagnosed with NPT and treated with surgical intervention at our center from April 2013-April 2023. The dataset encompassed information such as the children's age, affected side, size of the contralateral testis, surgical procedures employed, outcomes, and histopathological examination results. All patients underwent physical examination and ultrasonography preoperatively, followed by a combination of laparoscopic exploration and exploration through inguinal or scrotal incisions during surgery. Long-term follow-up was conducted postoperatively. Results: A total of 476 cases comprising 504 NPT were included in this study: 302 cases on the left side, 146 cases on the right side, and 28 cases bilaterally. All patients underwent surgical treatment within 6-126 months (median 13 months). During laparoscopic exploration, blind-ended VDSV were found in 90 testes (72 on the left side, 18 on the right side), while exploration through inguinal or scrotal incisions revealed 52 (57.8%) testicular nodules with atrophy, which were excised, leaving 38 (42.2%) without any findings. Histopathological examination of atrophic nodules revealed fibrosis as the most common finding in 41 cases (78.8%), followed by involvement of the vas deferens in 33 cases (63.5%), calcification in 24 cases (46.2%), epididymis in 23 cases (44.2%), and hemosiderin deposition in 7 cases (13.6%). Fibrosis, calcification, hemosiderin deposition, involvement of the vas deferens, and epididymis were found in combination in 47 specimens (90.4%). Seminiferous tubules (SNT) were found in 3 specimens (5.7%), and germ cells (GC) were found in 1 specimen (1.9%). Conclusion: The presence of blind-ended VDSV during laparoscopic exploration of NPT does not necessarily indicate testicular absence or disappearance. It is possible that atrophic testicular nodules are located within the inguinal canal or scrotum. This understanding contributes to the management of non-palpable testes. Considering their unpredictable malignant potential, we recommend excision.

Screening, characterization and mechanism of a potential stabiliser for nisin nanoliposomes with high encapsulation efficiency.

The encapsulation efficiency (EE%) reflects the amount of bioactive components that can be loaded into nanoliposomes. Obtaining a suitable nanoliposome stabiliser may be the key to improving their EE%. In this study, three polyphenols were screened as stabilisers of nanoliposomes with high nisin EE%, with curcumin nanoliposomes (Cu-NLs) exhibiting the best performance (EE% = 95.94%). Characterizations of particle size, PDI and zeta potential indicate that the Cu-NLs had good uniformity and stability. TEM found that nisin accumulated at the edges of the Cu-NLs' phospholipid layer. DSC and FT-IR revealed that curcumin was involved in the formation of the phospholipid layer and altered its structure. FT-IR and molecular docking simulations indicate that the interactions between curcumin and nisin are mainly hydrogen bonding and hydrophobic. In whole milk, Cu-NLs effectively protected nisin activity. This study provides an effective strategy for improving the EE% of nanoliposomes loaded with nisin and other bacteriocins.

Fried Soybean Oil Causes Systemic Low-Grade Inflammation by Disrupting the Balance of Gut Microbiota in Mice.

Previous reports have mainly investigated the long-term effects (>30 d), such as gut microbiota dysbiosis and systemic low-grade inflammation, in mice fed fried oil. However, short-term intake of deep-fried oil is more likely to occur in daily life, and such studies are lacking. This study aimed to investigate the short-term effects of fried oil intake on systemic low-grade inflammation. Male Kunming mice were fed non-fried soybean oil or low (25%), medium (50%), or high (100%)-fried oil at 4.4 g/kg for 6 d. Serum and fecal samples were collected on day 7. In all groups fed fried oil, the serum levels of tumor necrosis factor (TNF-α) were significantly elevated 2-4-fold. Among the gut microbiota, the abundance of Alloprevotella significantly decreased by up to 76%, while Lactobacilli significantly increased by up to 385%. The fecal valeric acid content was significantly increased and positively correlated with TNF-α levels. Both valeric acid and TNF-α levels were positively correlated with the abundance of Lactobacilli and negatively correlated with that of Alloprevotella. In summary, a short-term ingestion of even low doses of fried oil alters the gut microbiota Alloprevotella and Lactobacilli and increases fecal valeric acid content, which correlates with increased serum TNF-α levels.

A Tripeptide (Ser-Arg-Pro, SRP) from Sipunculus nudus L. Improves Cadmium-Induced Acute Kidney Injury by Targeting the MAPK, Inflammatory, and Apoptosis Pathways in Mice.

Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from Sipunculus nudus L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1ß, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.

Case report: Long-term intracranial effect of zimberelimab monotherapy following surgical resection of high PD-L1-expressing brain metastases from NSCLC.

Non-small cell lung cancer (NSCLC) accounted for the majority of lung cancer cases worldwide. Brain metastases (BM) frequently complicate NSCLC and portend a dismal prognosis. To control neurological symptoms, surgical resection is commonly followed by brain radiotherapy (RT). However, RT is often complicated by neurotoxicity. For patients with tumors that harbor positive driver genes, tyrosine kinase inhibitors are considered the standard of care. Nevertheless, treatment options for those without driver gene mutations are still debated. Programmed death receptor 1 (PD-1)/ligand 1 (PD-L1) inhibition has emerged as a novel therapeutic strategy for NSCLC patients with PD-L1-positive tumors, as well as for those with asymptomatic BM. However, the effect of anti-PD-1 antibodies on active BM within such specific populations is undetermined. Herein we present a case of a 65-year-old patient with NSCLC and high PD-L1-expressing BM. The patient underwent surgical resection of BM followed by first-line monotherapy with 31 cycles of zimberelimab, a novel anti-PD-1 antibody, and has already achieved 24 months of progression-free survival and intracranial recurrence-free survival. To our knowledge, this is the first report regarding the intracranial effect of zimberelimab on BM from primary lung cancer. This case report might facilitate an understanding of the intracranial effects of different anti-PD-1 antibodies for such populations.

Persistent Cytopenia After CD19 CAR T Therapy in Relapsed/Refractory DLBCL Patients Could Be a Predictor of Efficacy and Side Effects.

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.

Efficacy and side effects of anti-CD19 CAR T-cell therapy in patients with relapsed/refractory gastrointestinal lymphoma.

INTRODUCTION: Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy was approved as a very effective salvage strategy in relapsed/refractory (R/R) B cell lymphoma, the experience in R/R gastrointestinal (GI) lymphoma is still insufficient. METHODS: We summarized the efficacy and side effects of anti-CD19 CAR T-cell therapy in 12 patients with R/R GI lymphoma. Based on literature, the R/R GI lymphoma patients were divided into subgroups with different characteristics: Bulky/No bulky disease, Gastric/Gastrointestinal involvement, Gastrointestinal/Combined extra-gastrointestinal lesions, Ulcer/Lumps or nodules type, With/without gastrointestinal bleeding. RESULTS: The objective response rate (ORR) was 66.67% in these 12 patients. The ORR was 83.33% in no bulky disease group, 80.00% in gastric involvement group, 100.00% in ulcer type group, and 80.00% in no gastrointestinal bleeding group. The CR rate was 33.33% in these 12 patients. The CR was 50.0% in no bulky disease group, 60.00% in gastric involvement group, and 80.00% in ulcer type group. The PFS and OS rate of the 12 patients at 6 months after infusion were 54.55% and 58.33%, respectively. The overall survival (OS) at 6 months was higher in no bulky disease group. There was no difference of the OS or the progression free survival (PFS) at 6 months between the other groups. The mean peak of CAR-T cells and Cytokine Release Syndrome (CRS) grade were higher in gastrointestinal lesions group. The mean peak of IFN-γ and CRS grade were higher in gastrointestinal bleeding group. Four out of six patients in group of gastrointestinal lesions group were patient with high tumor burden. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding. CONCLUSIONS: The ORR and CR of high tumor load, gastrointestinal involvement, lumps or nodules type and gastrointestinal bleeding group were lower. The CRS grade was higher in gastrointestinal lesions group and in gastrointestinal bleeding group. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding.

An "off-on" fluorescent nanosensor for the detection of cadmium ions based on APDC-etched CdTe/CdS/SiO2 quantum dots.

In this study, we have developed a novel fluorescent "OFF-ON" quantum dots (QDs) sensor based on CdTe/CdS/SiO2 cores. Ammonium pyrrolidine dithiocarbamate (APDC), ethylenediamine tetraacetic acid (EDTA), and 1,10-phenanthroline (Phen) served as potential chemical etchants. Among these three etchants, APDC exhibited the most pronounced quenching effect (94.06%). The APDC-etched CdTe/CdS/SiO2 QDs demonstrated excellent optical properties: the fluorescence of the APDC-etched CdTe/CdS/SiO2 QDs system (excitation wavelength: 365 nm and emission wavelength: 622 nm) was significantly and selectively restored upon the addition of cadmium ions (Cd2+) (89.22%), compared to 15 other metal ions. The linear response of the APDC-etched CdTe/CdS/SiO2 QDs was observed within the cadmium ion (Cd2+) concentration ranges of 0-20 µmol L-1 and 20-160 µmol L-1 under optimized conditions (APDC: 300 µmol L-1, pH: 7.0, reaction time: 10 min). The detection limit (LOD) of the APDC-etched CdTe/CdS/SiO2 QDs for Cd2+ was 0.3451 µmol L-1 in the range of 0-20 µmol L-1. The LOD achieved by the QDs in this study surpasses that of the majority of previously reported nanomaterials. The feasibility of using APDC-etched CdTe/CdS/SiO2 QDs for Cd2+ detection in seawater, freshwater, and milk samples was verified, with average recoveries of 95.27%-110.68%, 92%-106.47%, and 90.73%-111.60%, respectively, demonstrating satisfactory analytical precision (RSD ≤ 8.26).

High-intensity interval training versus moderate-intensity continuous training for localized prostate cancer under active surveillance: a systematic review and network meta-analysis.

BACKGROUND: High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been increasingly adopted for localized prostate cancer (PCa) under active surveillance (AS). However, it is unclear which training modality is the most favorable in terms of cardiorespiratory fitness and biochemical progression. METHODS: We searched PubMed, Cochrane and Embase for relevant RCTs. PRISMA guideline was adopted to ensure optimal conduct of this study. Serum prostate specific antigen (PSA) and peak VO2 were selected as primary outcomes and PSA doubling time (PSADT) and testosterone were selected as secondary outcomes. Only articles written in English were included. Cochrane risk-of-bias tool was used for risk of bias evaluation. RESULTS: A total of 501 studies were selected. Six RCTs with 222 patients were included for data extraction and analysis. High-intensity interval training (HIIT) group demonstrated significantly lower PSA compared with usual care (UC) (MD = -1.4; 95%CI = -2.77 to -0.03) and moderate-intensity continuous training (MICT) group (MD = -1.67; 95%CI = -3.30 to -0.05). Both HIIT and MICT showed significantly improved peak VO2 compared with UC. No significant difference was observed in PSADT and testosterone among different training modalities and UC. Regarding peak VO2, MICT had the highest surface under cumulative ranking curve (SUCRA) scores (98.1%). For serum PSA, HIIT had the highest probability (97.8%) to be the training with the highest efficacy. The potential source of bias mainly came from poorly performed allocation concealment and blinding strategies. CONCLUSIONS: The present study indicated that HIIT and MICT showed considerable cardiorespiratory benefits for localized PCa. HIIT was preferred over MICT in biochemical progression control in terms of decreasing serum PSA levels. However, MICT was favored over HIIT regarding cardiorespiratory benefits. The findings of this study may facilitate future lifestyle intervention, particularly in the form of physical training, for individuals diagnosed with localized PCa under AS.

Development and validation of a nomogram based on CT texture analysis for discriminating minimally invasive adenocarcinoma from glandular precursor lesions in sub­centimeter pulmonary ground glass nodules.

In a recent reclassification, adenocarcinoma in situ has been redefined as a glandular precursor lesion (GPL), alongside adenomatous hyperplasia. This updated classification necessitates corresponding adaptations in clinical diagnostic and therapeutic protocols. Consequently, the present study aimed to construct and validate a nomogram utilizing computed tomography (CT) texture features to effectively discriminate between minimally invasive adenocarcinoma (MIA) and GPL within sub-centimeter pulmonary ground glass nodules (GGNs). To achieve this objective, the present study employed rigorous statistical methodologies, including the Mann-Whitney U test and binary logistic regression analysis, to identify distinguishing features and establish predictive models. Subsequently, the diagnostic performance of these models underwent evaluation through receiver operating characteristic (ROC) curves. The area under the curve (AUC) in ROC curves was compared using DeLong's test. Additionally, the nomogram was constructed using R software and its diagnostic performance was validated through calibration curves. Within both the training and validation datasets, the AUCs were observed to be 0.992 [95% confidence interval (CI): 0.980-1.000] and 0.975 (95% CI: 0.935-1.000), respectively. DeLong's test revealed significant disparities in the AUCs between the nomogram and single-parameter models (P<0.001). Furthermore, calibration curves demonstrated concordance between the training and validation datasets. In conclusion, the application of a CT texture-based nomogram model has demonstrated aptitude in differentiating between MIA and GPL within sub-centimeter GGNs. This model streamlines the identification of optimal surgical interventions and enhances the sphere of clinical decision-making and management.

Cereibacter flavus sp. nov., a novel member of the family Rhodobacteraceae isolated from seawater of the South China Sea and reclassification of Rhodobacter alkalitolerans as Cereibacter alkalitolerans comb. nov.

A Gram-stain-negative, aerobic, motile, ovoid-shaped and yellow-coloured strain, designated SYSU M79828T, was isolated from seawater collected from the South China Sea. Growth of this strain was observed at 4-37 °C (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-6% NaCl (optimum, 3.0 %, w/v). The respiratory quinone was found to be Q-10. Major fatty acid constituents were C18 : 1 ω7c/C18 : 1 ω6c, C18 : 1 ω7c11-methyl and C18 : 0 (>5 % of total). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, two unidentified phospholipid, one unidentified lipid and an unidentified glycolipid. The genomic DNA G+C content was 64.5 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M79828T belonged to the genus Cereibacter and had the highest sequences similarity to 'Rhodobacter xinxiangensis' TJ48T (98.41 %). Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterizations, we consider that strain SYSU M79828T represents a novel species of the genus Cereibacter, for which the name Cereibacter flavus sp. nov. is proposed. The type strain is SYSU M79828T (=GDMCC 1.3803T=KCTC 92893T). In addition, according to the results of phylogenetic analysis and similar taxonomic characteristics, we propose that Rhodobacter alkalitolerans should be reclassified as Cereibacter alkalitolerans comb. nov.

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma: A case report and review of literature.

BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer with a poor prognosis at advanced stage, and the standard first-line treatment for inoperable patients is chemotherapy. Although combining programmed cell death 1 (PD-1) inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors, there are few reports regarding initial immunochemotherapy in advanced MPeM. CASE SUMMARY: Here, to our knowledge, we present the first case of a patient with epithelioid subtype MPeM, who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival (PFS) and good tolerance. A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen. Computed tomography revealed a solid mass in the lower abdomen, which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy. The patient received eight cycles of pemetrexed 800 mg (day 1), cisplatin 60/50 mg (day 1-2), and zimberelimab (PD-1 inhibitor) 240 mg (day 1) every 3 wk. He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms. The best tumor response was partial remission with a final PFS of 7 mo. No immune-related adverse event occurred during the combination treatment. CONCLUSION: The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Alsobacter ponti sp. nov., a novel denitrification and sulfate reduction bacterium isolated from Pearl River sediment.

A Gram-staining negative, aerobic, motile, and short rods strain, designated SYSU M60028T, was isolated from a Pearl River sediment sample in Guangzhou, Guangdong, China. The isolate could be able to grow at pH 6.0-8.0 (optimum, pH 7.0), 25-37 °C (optimum, 28 °C) and in the presence of 0-2% (w/v) NaCl (optimum, 0% NaCl). The cellular polar lipids of this strain were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, one unidentified aminolipid and three unidentified lipids. The respiratory quinone of SYSU M60028T was found to be Q-10. The major fatty acids (> 5% of total) were summed feature 8, C16:0, and C18:1 ω7c 11-methy1. The genomic DNA G + C content was 69.9%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M60028T belonged to the genus Alsobacter and had the highest sequences similarities to Alsobacter metallidurans SK200a-9T (96.87%) and Alsobacter soli SH9T (96.87%). Based on the phenotypic, genotypic, and phylogenetic data, strain SYSU M0028T should be considered to represent a novel species of the genus Alsobacter, for which the name Alsobacter ponti sp. nov. is proposed. The type strain is SYSU M60028T (= CGMCC 1.19341T = KCTC 92046T).

L-Cysteine hydrochloride inhibits Aspergillus flavus growth and AFB1 synthesis by disrupting cell structure and antioxidant system balance.

Aflatoxin B1 (AFB1) is the most potent known naturally occurring carcinogen and pose an immense threat to food safety and human health. L-Cysteine hydrochloride (L-CH) is a food additive often used as a fruit and vegetable preservative and also to approved bread consistency. In this study, we investigated the effects and mechanisms of L-CH as an antimicrobial on the growth of Aspergillus flavus (A. flavus) and AFB1 biosynthesis. L-CH significantly inhibited A. flavus mycelial growth, affected mycelial morphology and AFB1 synthesis. Furthermore, L-CH induced glutathione (GSH) synthesis which scavenged intracellular reactive oxygen species (ROS). RNA-Seq indicated that L-CH inhibited hyphal branching, and spore and sclerotia formation by controlling cell wall and spore development-related genes. Activation of the GSH metabolic pathway eliminated intracellular ROS, leading to hyphal dwarfing. L-CH treatment downregulated most of the Aflatoxin (AF) cluster genes and aflS, aflR, AFLA_091090 transcription factors. This study provides new insights into the molecular mechanism of L-CH control of A. flavus and AFB1 foundation. We believe that L-CH could be used as a food additive to control AFB1 in foods and also in the environment.

Glutaredoxin 2 protects lens epithelial cells from epithelial-mesenchymal transition by suppressing mitochondrial oxidative stress-related upregulation of integrin-linked kinase.

Glutaredoxin 2 (Grx2), a mitochondrial glutathione-dependent oxidoreductase, is crucial for maintaining redox homeostasis and cellular functions in the lens. The oxidative stress-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is related to posterior capsule opacification. In this study, we investigated the effects of Grx2 on oxidative stress-induced EMT in LECs during posterior capsule opacification. We found that Grx2 expression was substantially decreased during the EMT of LECs and in a mouse model of cataract surgery. Deletion of Grx2 aggravated the generation of reactive oxygen species, including those that are mitochondria-derived, and promoted the proliferation and EMT of the LECs. This was reversed by Grx2 overexpression. In vivo, proteomic liquid chromatography-mass spectrometry analysis showed that integrin-linked kinase (ILK) was significantly upregulated in the lens posterior capsule of a Grx2 knockout (KO) mouse model. Compared with that of the wild-type group, the expression of ILK and EMT markers was increased in the Grx2 KO group which was reversed in the Grx2 knock-in group. Inhibition of ILK partially blocked Grx2 knockdown-induced EMT and prevented the increased phosphorylation of Akt and GSK-3ß and the nuclear translocation of ß-catenin in the Grx2 KO group. Finally, inhibition of the Wnt/ß-catenin pathway partially blocked the Grx2 knockdown-induced EMT. In conclusion, we demonstrated that Grx2 protects LECs from oxidative stress-related EMT by regulating the ILK/Akt/GSK-3ß axis.

The diagnosis and treatment of testicular torsion in children with non-scrotal initial symptoms.

Objective: To explore the clinical characteristics of testicular torsion in children with non-scrotal initial symptoms who were misdiagnosed. Methods: A retrospective analysis of 73 cases children with testicular torsion and non-scrotal symptoms who were admitted to our department from October 2013 to December 2021 was performed. Patients were divided into misdiagnosis (27 cases) and clear diagnosis at first visit (46 cases) groups. Clinical data, including age at surgery, clinical presentation, physical examination, number of visits (≥2 times), affected side, time from initial symptoms to surgery, and surgical outcomes, were collected. The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score was calculated and analyzed. Results: Statistically significant differences between the misdiagnosis and clear diagnosis groups were seen in the time from initial symptoms to surgery, the number of visits, the degree of testicular torsion, and the rate of orchiectomy (P < 0.05). There were no statistically significant differences (P > 0.05) in age, affected side, TWIST score, guardian, direction of testicular torsion, intra-vaginal or extra-vaginal torsion, and Arda classification. Postoperative follow-up was 6-40 months. Of the 36 patients who required an orchiopexy, 1 had testicular atrophy at six months and 2 were lost to follow-up. The contralateral testis of the 37 children who underwent orchiectomies developed normally without torsion. Conclusions: The clinical manifestations of testicular torsion in children are diverse and can easily lead to misdiagnosis. Guardians should be aware of this pathology and seek timely medical attention. When the initial diagnosis and treatment of testicular torsion is difficult, the TWIST score during the physical examination may be useful, especially for patients with intermediate-to-high risk scores. Color Doppler ultrasound can assist in making the diagnosis, but when testicular torsion is highly suspected, routine ultrasound is not necessary as it may lead to delayed surgical treatment.

Cadmium-chelating ability of the siderophore DHBS secreted by Leclercia adecarboxylata FCH-CR2 and its action mechanism.

As one of the most accumulative toxic heavy metals, cadmium (Cd) poses a major threat to human health. Bacterial siderophores, as small molecules with metal-absorbing ability, have great potential activity for Cd-reduction. In this study, the siderophore-producing bacterialstrain FCH-CR2 was isolated from a high-Cd contaminated soil using the CAS method. Leclercia adecarboxylata was identified through 16S rRNA sequence, homology analysis, colony morphology, physiological and biochemical tests. A siderophore, catechol type 2,3-dihydroxy-N-benzoyl-l-serine (DHBS) secreted by FCH-CR2, was purified using RP-HPLC and identified by LC-MS/MS. Intraperitoneal injection of DHBS significantly increased fecal Cd levels, and reduced Cd accumulation in organs. In density flooding theory (DFT) analysis, DHBS may bind to Cd via the hydroxyl site on the benzene ring. Besides, the isothermal titration calorimetry (ITC) assay revealed that the formation of Cd-DHBS is a spontaneous and endothermic reaction with ΔG = -21.4 kJ/mol and ΔH = 1.51 ± 0.142 kJ/mol.

Blinatumomab as salvage therapy in patients with relapsed/refractory B-ALL who have failed/progressed after anti-CD19-CAR T therapy.

BACKGROUND: Anti-CD19 chimeric antigen receptors (CARs) T-cell therapy has been shown to have excellent efficacy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). But many patients are refractory to anti-CD19-CAR T-cell therapy or relapse again. METHODS: Five patients with R/R B-ALL did not respond to anti-CD19-CAR T-cell therapy or had a disease progression again after CAR-T cell therapy. They received a salvage therapy of Blinatumomab. The clinical response, CD19 expression on ALL cells, the proportion of CD3+ T cells, level of cytokine levels of interleukin-6 (IL-6), hematological toxicity, grade of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxic syndrome (ICANS) were observed in salvage therapy of Blinatumomab. RESULTS: Four patients obtained CR/CRi, even in patients without high expression of CD19 in B-ALL cells, while the other patient received NR after Blinatumomab therapy. The CD19 expression on ALL cells, the proportion of CD3+ T cells, and CD3+CD8+ T cells were deficient in Pt 5, who obtained PR in Blinatumomab therapy. One patient (Pt 3) was diagnosed with grade 0 hematological toxicity. The other four patients were diagnosed with grades 2-3 of hematological toxicity. The CRS was grade 0/one patient, grade 1/three, and grade 2/one. The ICANS was grade 0/four patients, grade 1/one. Rhizopus microsporus pneumonia and cryptococcal encephalopathy in two patients were controlled during Blinatumomab therapy. CONCLUSIONS: Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in R/R B-ALL patients without high expression of CD19 in B-ALL cells, patients with CNS leukemia or co-infection.Key messagesSome R/R B-ALL patients did not respond to anti-CD19 CAR T-cell therapy or had a disease progression again. Effective and safe salvage therapy for such patients remains to be explored.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients without high expression of CD19 in B-ALL cells.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients with CNS leukemia or co-infection.

Efficacy and safety-related factors of BTK inhibitors as a bridge to CAR-T therapy in R/R FL.

Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy has achieved satisfactory results in relapsed/refractory (R/R) follicular lymphoma (FL), patients with R/R FL and high-risk disease characteristics, previous hematopoietic stem cell transplantation, bulky disease, and progression of disease within 2 years (POD24) had a low complete response (CR). Twenty-seven patients with R/R FL, later disease stages, higher tumor burden, or higher previous treatment lines who had received Bruton tyrosine kinase (BTK) inhibitors before anti-CD19 CAR T cell therapy, or received BTK inhibitors as combination therapy, were included in this study. The clinical response and adverse events (AEs) in anti-CD19 CAR T cell therapy were observed. All patients with R/R FL who received BTK inhibitors combined with anti-CD19-CAR T cell therapy had later disease stages, higher tumor burden, and higher treatment lines than those who did not receive BTK inhibitor combination therapy. However, no difference in the clinical response was found between the two groups. The clinical response in the POD24 group was lower than that in the non-POD24 group; however, no difference in the clinical response was found between the FL and transformed FL (tFL) groups, between the follicular lymphoma international prognostic index (FLIPI) 1 1-2 and FLIPI 1 3-5 groups, and between the FLIPI 2 1-2 and FLIPI 2 3-5 groups. The mean anti-CD19 CAR T cell peak was higher in the CAR-T group with BTK inhibitor than in the CAR-T group without BTK inhibitor. Meanwhile, a higher proportion of patients in the non-POD24 group, FL group, and PR group achieved CR after 2 months. No difference in cytokine secretion was found between the CAR-T group with and without BTK inhibitors. It was higher in the non-POD24 group, FLIPI 1 3-5 group, and FLIPI 2 3-5 group. No difference in cytokine release syndrome and immune effector cell-associated neurotoxic syndrome grades was found between the CAR-T groups with or without BTK inhibitors and between the other groups. Poor prognostic factors, other than POD24, did not affect the clinical response to BTK inhibitors in combination with anti-CD19 CAR T cell therapy in patients with R/R FL. Therefore, BTK inhibitors combined with anti-CD19 CAR-T therapy may be an effective and safe approach for patients with R/R FL and high-risk factors.Trial registration: The study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and http://www.chictr.org.cn/index.aspx as ChiCTR1800019622.