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Yuan-Yuan Du, Xiao-Jing Yan, Yan-Jing Guo, Jing Wang, Xiao-Duo Wen, Nan Wang, Yi Yang Department of Gynecology and Obstetrics Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Yi YangDepartment of Gynecology and Obstetrics Ultrasound, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Chang’an District, Shijiazhuang, 050011, People’s Republic of ChinaTel/Fax +86 311 8609 5378Email yangyi_dr336@163.comBackground: To explore the value of transvaginal real-time shear wave elastography (SWE) in the diagnosis of endometrial lesions.Methods: A total of 140 female patients with endometrial lesions, confirmed by pathological results, were divided into three groups: 45 cases of endometrial polyps, 29 cases of endometrial hyperplasia and 66 cases of endometrial cancer. A total of 100 cases of normal endometrium were used as the control group, including 52 cases in the proliferative stage and 48 cases in the secretory stage. Transvaginal real-time shear wave elastography was performed in all four groups.Results: Emean, Emax and Esd were expressed as the average standard deviation. Among the control group, the results were 26.24± 9.74, 38.09± 9.18, and 4.25± 2.73 kPa, respectively, in the proliferative endometrium cases and 12.51± 7.46, 27.22± 11.32, 4.40± 2.52 kPa, respectively, in the secretory endometrium cases. Among the experimental group, the result was 15.68± 8.18, 27.28± 10.28 and 3.62± 1.81 kPa respectively in the endometrial polyps cases; 21.20 ± 12.57, 36.32 ± 15.04, and 5.09 ± 3.93 kPa in the endometrial hyperplasia cases; 49.36± 25.51, 86.66± 42.27 and 14.86± 10.63 kPa in the endometrial cancer cases. The difference was statistically significant (P < 0.05). When the truncation values of Emean, Emax and Esd were 28.50, 52.45 and 9.05 kPa, respectively, to distinguish between normal endometrium and endometrial cancer, Emax has the highest diagnostic value.Conclusion: Real-time SWE technology might be used as an auxiliary method in the diagnosis and differential diagnosis of endometrial cancer. More quantitative indicators are conducive to diagnosis.Keywords: ultrasound, endometrial lesions, real-time shear wave elastography, differential diagnosis

The Beijing Spectrometer (BES) detector is a general purpose solenoid detector at the Beijing Electron Positron Collider in Beijing, China. The recent upgrade of the initial BES detector to the improved BES II detector is described. A new drift chamber, time-of-flight counter, luminosity monitor compatible with a low-β lattice was built as well as the vertex chamber.

The Beijing Spectrometer (BES) detector is a general purpose solenoid detector at the Beijing Electron Positron Collider in Beijing, China. The recent upgrade of the initial BES detector to the improved BES II detector is described. A new drift chamber, time-of-flight counter, luminosity monitor compatible with a low-β lattice was built as well as the vertex chamber.

Objective: To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors. Methods: This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25-82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2-3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L-1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment. Results: Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2 =9.202, P =0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2 =40.526, P <0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2 =22.495, P <0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2 =15.899, P <0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6-126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion: The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Background: This study aimed to investigate the therapeutic efficacy and safety of Traditional medicine preparations (TMPs) given in combination with vascular endothelial growth factor receptor (VEGFR)-associated multi-targeted tyrosine kinase inhibitors (TKIs) for the treatment of middle to advanced-stage primary liver cancer (PLC)., Methods: This systematic literature survey employed 10 electronic databases and 2 clinical trial registration platforms to identify relevant studies on the use of TMPs + VEGFR-TKIs to treat patients with middle-advanced PLC. Furthermore, a meta-analysis was performed following the PRISMA guidelines using the risk ratio (RR) at 95% confidence intervals (CI) or standardized mean difference as effect measures., Results: A total of 26 studies comprising 1678 middle-advanced PLC patients were selected. The meta-analysis revealed that compared with VEGFR-TKI mono-treatment, the co-therapy of TMPs + VEGFR-TKIs considerably enhanced the objective response rate (RR = 1.49, 95% CI: 1.31-1.69), disease control rate (RR = 1.23, 95% CI: 1.16-1.30), and one-year overall survival (RR = 1.49, 95% CI: 1.28-1.74). Furthermore, the co-therapy was associated with reduced incidences of liver dysfunction (RR = 0.64, 95% CI: 0.45-0.91), proteinuria (RR = 0.43, 95% CI: 0.24-0.75), hypertension (RR = 0.66, 95% CI: 0.53-0.83), hand-foot skin reactions (RR = 0.63, 95% CI: 0.49-0.80), myelosuppression (RR = 0.63, 95% CI: 0.46-0.87), and gastrointestinal reactions (RR = 0.64, 95% CI: 0.45-0.92). Moreover, the co-therapy indicated no increase in the incidences of rash and fatigue., Conclusion: This systematic analysis revealed that co-therapy with TMPs + VEGFR-TKIs has a higher effectiveness and safety profile for treating middle-advanced PLC patients. However, further validation using randomized control trials is required., Prospero Registration No: CRD42022350634., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that predominantly affects the kidney and uterus. The occurrence of this tumor in the liver, particularly with simultaneous involvement of the liver and kidney, is exceedingly uncommon. Pathological diagnosis is the gold standard. PEComas usually show positive immunohistochemical staining for melanocytic (HMB-45, Melan-A) and myoid (SMA, muscle-specific actin) markers., Case Summary: We presented a noteworthy case of malignant PEComa affecting both the liver and kidney in a 53-year-old man with tuberous sclerosis complex (TSC). FAT2 and TP73 mutations in the kidney were identified and positive expression of diagnostic markers including HMB-45, Melan A, and TFE3 were detected. In addition, we demonstrated that hepatic artery perfusion chemotherapy was ineffective for hepatic PEComa, while surgery remained the most effective approach. Everolimus showed an excellent efficacy in the postoperative treatment of the tumor., Conclusion: Surgical treatment is preferred for malignant PEComa affecting liver and kidney, especially with TSC; everolimus is effective postoperatively., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested that lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, this research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment, and the associated immune-related adverse events (irAEs) have garnered significant attention, yet reports on associated immune related gastritis are limited. The diagnosis of immune related gastritis remains predominantly exclusionary, meanwhile its management diverges significantly from that of conventional gastritis. Current guidelines lack standardized grading criteria, and substantial data from large-scale, tertiary clinical studies are absent, therefore we conducted a systematic review of Medline, Web of Science, and Embase databases, identifying 31 articles from 2017 to December 31, 2023, involving 258 patients. Clinical manifestations included epigastric pain (53.1%), mucosal erythema (56.1%), and lymphocyte infiltration (48.6%). Corticosteroid therapy was common (94.7%), with 86.7% experiencing post-treatment improvement. 80% of patients can be diagnosed through endoscopy and pathology, while the remaining 20% may require PET-CT. Hormonal therapy is favored but diverges from standard management. Accurate diagnosis is crucial in managing immune related gastritis effectively.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It's recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC., (© 2024. The Author(s).)

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the changes and clinical significance of NOD like receptor protein 3 (NLRP3) inflammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury (SCI)., Methods: Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group, There were 48 males and 38 females, with an average age of (43.48±6.58) years old. And 100 healthy volunteers who underwent physical examination during the same time were selected as control group, including 56 males patients and 44 females patients, with an average age of (45.13±6.43) years old. Peripheral blood mononuclear cell (PBMC) were collected, and the mRNA expressions of NLRP3 and Caspase-1 were detected. Serum was collected and the levels of interleukin (IL)- 1β, IL-18 were detected. According to Frankel's grade, the SCI group was divided into complete injury patients and incomplete injury patients, and according to the Japanese Orthopedic Society (JOA) grade, the SCI group was divided into good prognosis group and poor prognosis group. The difference of NLRP3, Caspase-1, IL-1β, IL-18 among groups were compared, the influencing factors for poor prognosis in SCI patients was analyzed by Logistic regression., Results: The mRNA expression levels of NLRP3 (1.41±0.33) and Caspase-1 (1.44±0.35) in PBMC and the levels of IL-1β(45.34±13.22) pg·ml -1 , IL-18(40.95±8.77) pg·ml -1 in serum of SCI group were higher than those of the control group[(1.00±0.19), (1.00±0.16), (16.58±4.24) pg·ml -1 , (12.57±3.68) pg·ml -1 ] ( P <0.05). The mRNA expression levels of NLRP3(1.63±0.34) and Caspase-1 (1.67±0.27) in PBMC and the levels of IL-1β(51.09±11.10) pg·ml -1 , IL-18 (47.65±7.93) pg·ml -1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury [(1.31±0.27), (1.34±0.33), (42.85±13.36) pg·ml -1 , (38.05±7.48) pg·ml -1 ]( P <0.05). The mRNA expression levels of NLRP3 (1.66±0.31) and Caspase-1 (1.72±0.31)in PBMC and the levels of IL-1β(51.21±11.31) pg·ml -1 , IL-18 (45.70±7.25) pg·ml -1 in serum, the proportion of complete injury(21 patients), and the proportion of spinal cord edema or bleeding of patients(15 patients) with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26), (1.37±0.36), (42.79±13.25) pg·ml -1 、(38.90±8.63) pg·ml -1 , 5、20 cases]( P <0.05). Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing factors for poor prognosis in the SCI group ( P <0.05)., Conclusion: The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis, and NLRP3 expression can serve as a marker for evaluating prognosis.

Eleven undescribed isoquinoline alkaloids (1-8, 14, 15, and 24), along with 19 analogues (9-13, 16-23, and 25-30) were isolated from the barks of Alangium salviifolium. The structures of the undescribed compounds were elucidated through the analysis of their HR-ESI-MS, 1D and 2D NMR, IR, UV, and X-ray diffraction. The absolute configuration of 8 was established via the ECD calculation. Notably, compounds 1/2 and 3/4 were two pairs of C-14 epimers. The isolated alkaloids were evaluated for their cytotoxicity against various cancer cell lines, including SGC-7901, HeLa, K562, A549, BEL-7402, HepG2, and B16, β-carboline-benzoquinolizidine (14-22) and cepheline-type (24-28) alkaloids exhibited remarkable cytotoxicity, with IC 50 values ranging from 0.01 to 48.12 μM. Remarkably, compounds 17 and 21 demonstrated greater cytotoxicity than the positive control doxorubicin hydrochloride. Furthermore, a significant proportion of these bioactive alkaloids possess a C-1' epimer configuration. The exploration of their structure-activity relationship holds promise for directing future investigations into alkaloids derived from Alangium, potentially leading to novel insights and therapeutic advancements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (β=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with β ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved., Methods: In vivo, an animal model was established by intraperitoneal injection of 300 μg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 μg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation., Results: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1β, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased., Conclusion: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony., (© 2024. Huazhong University of Science and Technology.)

Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD., Methods: SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer；liver morphological changes were observed by Oil Red O staining；real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue., Results: In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4 th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated ( P <0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased ( P <0.01, P <0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased ( P <0.01, P <0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased ( P <0.01) in the SEA group at the 2 nd , 3 rd , and 4 th week, the expression of PERK and CHOP proteins at the 2 nd , 3 rd , 4 th week and ATF4 protein at 2 nd week in the liver tissue were decreased ( P <0.01, P <0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated ( P <0.05, P <0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased ( P <0.01, P <0.05) in the SEA and WEA groups at 3 rd and 4 th week, the expression of ATF4 proteins in the liver tissue was decreased ( P <0.01) in the SEA group at 3 rd and 4 th week, and the expression of CHOP proteins in the liver tissue was decreased ( P <0.01) in the SEA group at 4 th week and in the WEA group at 3 rd and 4 th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased ( P <0.05, P <0.01) in the SEA and WEA groups at 4 th week, the expression of PERK and CHOP proteins in the liver tissue was decreased ( P <0.01) in the SEA and WEA groups at 4 th week, and the expression of ATF4 protein in the liver tissue was decreased ( P <0.05) in the SEA group at 4 th week., Conclusions: EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect；the optimal effect was observed with EA intensity of 4 mA for 4 weeks.

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

Objectives: To investigate the effects of the elongated needling at the points of hand and foot yang meridians and the Governor Vessel combined with the routine acupuncture therapy on pain, balance function and muscle strength of the patients with post-stroke hemiplegia and central post-stroke pain (CPSP), and to investigate whether its therapeutic mechanism is related to antioxidant damage., Methods: Ninety-four patients with post-stroke hemiplegia and CPSP admitted from March 2020 to September 2021 were divided into a trial group (47 cases, 1 cases dropped out) and a control group (47 cases 3 cases dropped out). In the control group, the rehabilitation exercise combined with routine acupuncture therapy was used, and in the trial group, on the base of the treatment as the control group, the elongated needling at the points of hand and foot yang meridians and the Governor Vessel was supplemented. In the two groups, the treatment was given once daily, and 1 course of treatment was composed of 14 days, a total of 6 courses were required in the trial. Separately, before treatment, and 1, 2 and 3 months after treatment, between two groups, the score of visual analogue scale (VAS) and that of Berg balance scale (BBS), as well as muscle strength were compared；the neural function was evaluated using the national institutes of health stroke scale (NIHSS) and the serum contents of nitricoxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA in the patients., Results: Compared with those before treatment, VAS score and NIHSS score were all decreased ( P< 0.05) in the trial and the control group after 1 month, 2 months and 3 months of treatment, and BBS score was increased ( P< 0.05)；and the case proportion of muscle strength grade 4 and 5 was higher ( P< 0.05) in the trial group. In the control group, the proportion of grade 4 increased after treatment for 2 months ( P <0.05), and that of grade 4 and 5 increased after treatment for 3 months ( P <0.05). The serum contents of NOS and SOD were increased ( P <0.05), and MDA was decreased ( P <0.05) after 3 months of treatment in the two groups. In comparison with the control group at the same time point, VAS score and NIHSS score were lower ( P <0.05), BBS score higher ( P <0.05) and the muscle strength grade was improved ( P <0.05, P <0.01) after 1, 2 and 3 months of treatment, respectively；and the serum contents of NOS and SOD increased ( P <0.05), and MDA decreased ( P <0.05) after 3 months of treatment in the trial group., Conclusions: The elongated needling at the points of hand and foot yang meridians and the Governor Vessel, combined with the routine acupuncture therapy alleviates CPSP, improves balance and muscle strength and promotes the recovery of neural function in the patients with post-stroke hemiplegia, the mechanism may be related to antioxidant damage.

Autism spectrum disorder (ASD) is a multifaceted neuropsychiatric condition for which effective drug therapy for core clinical symptoms remains elusive. Lotusine, known for its neuroprotective properties in the treatment of neurological disorders, holds potential in addressing ASD. Nevertheless, its specific efficacy in ASD remains uncertain. This study aims to investigate the therapeutic potential of lotusine in ASD and elucidate the underlying molecular mechanisms. We induced an ASD mouse model through intracerebroventricular-propionic acid (ICV-PPA) injection for 7 days, followed by lotusine administration for 5 days. The efficacy of lotusine was evaluated through a battery of behavioral tests, including the three-chamber social test. The underlying mechanisms of lotusine action in ameliorating ASD-like behavior were investigated in the medial prefrontal cortex (mPFC) using whole-cell patch-clamp recordings, western blotting, immunofluorescence staining, molecular docking, and cellular thermal shift assay. The efficacy and mechanisms of lotusine were further validated in vitro. Lotusine effectively alleviated social deficits induced by ICV-PPA injection in mice by counteracting the reduction in miniature excitatory postsynaptic current frequency within the mPFC. Moreover, lotusine enhanced neuronal activity and ameliorated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor dysfunction in ICV-PPA infusion mice by upregulating c-fos, p-GluA1 Ser 845, and p-GluA1 Ser 831 protein levels within the mPFC. Our findings also suggest that lotusine may exert its effects through modulation of the D1 dopamine receptor (DRD1). Furthermore, the rescuing effects of lotusine were nullified by a DRD1 antagonist in PC12 cells. In summary, our results revealed that lotusine ameliorates ASD-like behavior through targeted modulation of DRD1, ultimately enhancing excitatory synaptic transmission. These findings highlight the potential of lotusine as a nutritional supplement in the treatment of ASD., (© 2024 John Wiley & Sons Ltd.)

Introduction: Personal care products (PCPs) contain a number of endocrine-disrupting chemicals (EDCs) that could potentially affect the reproductive function in women of childbearing age. However, studies focused on the effects of PCPs use on reproductive outcomes are very limited. The current study aimed to explore the relationships between PCPs use patterns and reproductive outcomes in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment., Methods: A total of 1500 women from the Tongji Reproductive and Environmental (TREE) study between December 2018 and January 2020 were included in this study. Participants provided characteristics of PCPs use within the previous three months. Retrieved oocyte number, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, cleavage rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth were followed up as reproductive endpoints. Generalized linear regression model was utilized to assess the associations between various categories of PCPs use and reproductive endpoints of IVF/ICSI., Results: After adjusting for relevant covariates, women who used skin care products ≥14 times per week had a reduction of 22.4% in the maturation rate (95% CI: -39.2%, -1.6%) compared to participants who did not use skin care products. After transferring fresh embryos, women who used cosmetics 1-2 times per week (adjusted OR = 2.2, 95% CI: 1.0, 4.8) or 3-7 times per week (adjusted OR = 2.5, 95% CI: 1.2, 5.2) had a higher possibility of miscarriage than those who did not use cosmetics. There was negative association between the use of gel or soap and the cleavage rate among women aged < 30 years old ( P for interaction = 0.01). Among women with BMI ≥ 24 kg/m 2 , the use of gel or soap was negatively associated with the blastocyst formation rate ( P for interaction = 0.04), while cosmetics use was negatively associated with the maturation rate ( P for interaction = 0.001)., Conclusion: Our findings suggest that the use of PCPs in women of reproductive age have a potential adverse impact on IVF/ICSI outcomes, particularly skin care and cosmetic products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Yao, Liu, Deng, Li, Liao, Tian, Wang, Du and Li.)

Sleep deprivation (SD) has led to a rise in cognitive impairment (CI) cases. Kaempferol (KMP), known for its anti-inflammatory and antiapoptotic properties, holds promise in countering SD-induced CI. Experimental validation using a sleep-deprived CI model confirmed KMP's efficacy in mitigating CI. Immunofluorescence investigations emphasized diminished activation of astrocytes and reduced the proliferation of microglia in the hippocampus of mice subjected to SD. Subsequently, network pharmacological analyses were conducted and found that KMP may be closely related to the mitogen-activated protein kinase (MAPK) pathway in SD-induced CI. The influence of KMP on the MAPK pathway was verified by the observed decrease in the expression of phosphorylated JNK (p-JNK) and p38 (p-p38). Analyzing hippocampal AMPARS and NMDARS expression indicated KMP's ability to enhance GluA1 phosphorylation (Ser831 and Ser845) and GluN2A levels. Patch clamp assays demonstrated heightened excitatory transmitter transmission in the hippocampus, suggesting KMP's positive influence. Overall, KMP combats neuroinflammation via MAPK inhibition, augments synaptic function, and addresses learning and memory dysfunction in sleep-deprived mice., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m 2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ 2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P =0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

We report a chiral phosphoric acid catalyzed apparent hydrolytic ring-opening reaction of racemic aziridines in a regiodivergent parallel kinetic resolution manner. Harnessing the acyloxy-assisted strategy, the highly stereocontrolled nucleophilic ring-opening of aziridines with water is achieved. Different kinds of aziridines are applicable in the process, giving a variety of enantioenriched aromatic or aliphatic amino alcohols with up to 99% yields and up to >99.5 : 0.5 enantiomeric ratio. Preliminary mechanistic study as well as product elaborations were inducted as well., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the natural history and risk factors for continued allergy in infants with IgE-mediated cow's milk protein allergy (CMPA). Methods: This was a prospective cohort study that included 72 infants under 24 months of age diagnosed with IgE-mediated CMPA in the allergy clinic of the Children's Hospital, Capital Institute of Pediatrics from October 2019 to November 2020. General information, clinical manifestations, serum total IgE, cow's milk specific IgE, and cow's milk protein component specific IgE were collected. Follow-ups were conducted at 24 and 36 months of age, and the patients were divided into the persistent allergy group and the tolerance group based on whether they developed cow's milk tolerance at 36 months of age. Mann-Whitney U test, chi-square test, and binary Logistic regression were used for intergroup comparison and multivariate analysis. Results: Among the 72 CMPA children, there were 42 boys and 30 girls, with an age of 10 (7, 15) months at enrollment. Cow's milk protein tolerance was observed in 32 cases (44%) and 46 cases (64%) at 24 and 36 months of age, respectively. There were 26 cases in the persistent allergy group and 46 cases in the tolerance group. The proportion of respiratory symptoms, history of wheezing, positive specific IgE for α-lactalbumin and the total IgE level in the persistent allergy group were higher than that in the tolerance group (7 cases (27%) vs. 0, 6 cases (23%) vs. 2 cases (4%), 67% (14/21) vs. 26% (10/39), 225 (151, 616) vs. 48 (21, 185) kU/L, χ 2 =10.82, 4.16, 9.57, Z =4.07, all P <0.05). Multivariate Logistic regression analysis showed that anaphylaxis ( OR =21.14, 95% CI 2.55-175.14, P =0.005), a history of allergic rhinitis ( OR =5.94, 95% CI 1.54-22.86, P =0.005), elevated milk specific IgE ( OR =1.04, 95% CI 1.01-1.08, P =0.024), and positive casein specific IgE ( OR =6.64, 95% CI 1.39-31.69, P =0.018) were risk factors for continuous CMPA. Conclusions: Most infants with IgE-mediated CMPA can achieve tolerance within 3 years. Anaphylaxis, a history of allergic rhinitis, elevated milk specific IgE levels, and casein sensitization are risk factors for continuous allergy.

Objective: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL)., Methods: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits., Results: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death ( P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT ( P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 ( r =0.867) and IL-17A ( r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A ( r =0.827), IL-6 and IL-10 ( r =0.823) were highly positively correlated., Conclusion: Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

This study explored the protective effect and mechanism of hydrogen‑rich saline (HRS) on the neurological function of mice with cerebral ischemia. Effects of HRS on neurological function in mice with cerebral ischemia were evaluated by neurological function scores. Infarct volume and histological damage were evaluated by 2,3,5‑triphenyl tetrazolium chloride staining (TTC staining). Golgi‑Cox staining was conducted to measure the morphological changes of neuronal dendrites and dendritic spines. The expression of neuronal markers was detected by immunofluorescence. Western blot was used to detect protein expression. The infarct volume of mice in the HRS‑H group decreased significantly compared to that of the distal middle cerebral artery occlusion (dMCAO) group. Mice in the HRS‑H group had a lower neurological deficit score than that in the dMCAO group. Compared to the dMCAO group, the activity of superoxide dismutase (SOD) and the level of glutathione (GSH) significantly increased in the HRS‑H group. Compared with the dMCAO group, the number of apoptotic cells in the HRS‑H group decreased. Administration of HRS was shown to be able to decrease cavitation of the brain cortex after ischemia. The spine density in the HRS‑H group increased compared to that of the dMCAO group. In the in vitro experiment, compared with the oxygen‑glucose deprivation (OGD) group, the active oxygen content in the 75% HRM group decreased, and the mitochondrial membrane potential and adenosine triphosphate (ATP) content increased. Compared with the OGD group, the ratio of P‑AMPK and the levels of LC3II/LC3I in the hydrogen‑rich medium (HRM) group was upregulated, and P‑mTOR levels and P62 levels in the HRM group were down‑regulated. HRS can enhance neuroplasticity after ischemia and promote neurological recovery in mice with cerebral ischemia, which may involve the autophagy pathway mediated by the AMPK/mTOR signaling pathway.

In recent years, the influence of historical geological and climatic events on the evolution of flora and fauna in the Tibetan Plateau has been a hot research topic. The Qilian Mountain region is one of the most important sources of biodiversity on the Qinghai-Tibet Plateau. Many species existed in the region during the Pleistocene glacial oscillation, and the complex geographical environment provided suitable conditions for the survival of local species. The shrinkage, expansion, and transfer of the distribution range and population size of species have significant effects on genetic diversity and intraspecific differentiation. To reveal the effects of geological uplift and climate oscillation on the evolution of fish populations in the Qilian Mountains, we investigated the genetic structure, phylogenetic relationship, and phylogeographical characteristics of genus Triplophysa species in the Qilian Mountains using the mitochondrial DNA gene (COI), three nuclear genes (RAG1, sRH, and Myh6) and 11 pairs of nuclear microsatellite markers. We collected 11 species of genus Triplophysa living in the Qilian Mountains, among which Triplophysa hsutschouensis and Triplophysa papillosolabiata are widely distributed in the rivers on the northern slope of the Qilian Mountains. There was a high degree of lineage differentiation among species, and the genetic diversity of endemic species was low. The different geographical groups of T. papillosolabiata presented some allogeneic adaptation and differentiation, which was closely related to the changes in the river system. Except for the population expansion event of T. hsutschouensis during the last glacial period of the Qinghai-Tibet Plateau (0.025 MYA), the population sizes of other plateau loach species remained stable without significant population expansion. Starting from the east and west sides of the Qilian Mountains, T. hsutschouensis , and T. papillosolabiata showed two species colonization routes in opposite directions. The geological events of the uplift of the Qinghai-Tibet Plateau and the climatic oscillation of the Quaternary glaciation had a great influence on the genetic structure of the plateau loach in the Qilian Mountains, which promoted the genetic differentiation of the plateau loach and formed some unique new species. The results of this study have important guiding significance for fish habitat protection in the Qilian Mountains., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

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

Background: Ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed., Results: In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p-, m-, and o-ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two-electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m-ABFIP exhibited the most significant difference of insecticidal activity by about 90- and 5-fold to mosquito larvae between non-irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m-ABFIP and DTFIP1 enable optical control over the homomeric LsRDL-type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)-type GABAR by photoisomerization., Conclusion: Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA-dependent behavior. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Background: Although Parkinson's disease (PD) is the second most common neurodegenerative disorder, pregnancy in patients with PD is a relatively rare occurrence because the most common age of onset of PD is beyond the childbearing age, except in patients with Young-Onset PD (YOPD) caused by parkin RBR E3 ubiquitin protein ligase ( PRKN ) mutations., Case: In this study, we report the case of a 30-year-old Chinese woman who was affected by PRKN -associated YOPD and was treated with levodopa/benserazide during pregnancy. She gave birth to a healthy baby boy with an Apgar score of 9 through an uncomplicated vaginal delivery., Conclusion: This case further suggests that levodopa/benserazide during pregnancy is safe in the treatment of PRKN -associated YOPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Dong, Peng, Liu, Wang, Li, Du, Zhang and Zong.)

Objectives: The present study aims to evaluate the clinical application values of ultrasound real-time shear wave elastography (SWE) in the diagnosis and differential diagnosis of cervical cancer (CC)., Methods: A total of 285 married female patients were screened and divided into three groups according to the results of the pathological examination and the cervical ThinPrep cytologic test: 1) the CC group (n = 94); 2) the cervical intraepithelial neoplasia (CIN) group (n = 91); and 3) the normal control group (n = 100). The maximum Young's modulus (Emax), mean Young's modulus (Emean), minimum Young's modulus (Emin), and Young's modulus stability (Esd) in each group were measured and statistically analyzed., Results: There were no statistically significant differences in Emax, Emean, Emin, and Esd values between the anterior and posterior cervical walls, premenopausal and postmenopausal women, and nonparturient and parturient women in the normal control group. The Emax, Emean, Emin, and Esd values in the CIN group showed no statistically significant differences in different periods when compared with the control group. The differences between the normal control group and the CC group were statistically significant; the CC group showed no statistically significant differences in Emax, Emean, Emin, and Esd values at different clinical stages and in different pathological types. The cutoff value of Emax for CC diagnosis, which was of the highest accuracy (89.7%), was 43.48 kpa., Conclusion: Ultrasound real-time SWE can be applied to CC diagnosis., (© 2022 American Institute of Ultrasound in Medicine.)

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.

Sulfur is essential for plant growth, and the uptake of sulfate by plant roots is the primary source of plant sulfur. Previous studies have shown that the OAS-TL gene is a key enzyme in the sulfur metabolic pathway and regulates cysteine (Cys) synthase production. However, the interaction mechanism of the glycine max OAS-TL3 Cys synthase ( OAS-TL3 ) gene on soybean root morphology construction and seed protein accumulation is unclear. This study shows that mutant M18 has better root growth and development, higher seed protein content, and higher methionine (Met) content in sulfur-containing amino acids than wild-type JN18. By transcriptome sequencing, the differentially expressed OAS-TL3 gene was targeted in the mutant M18 root line. The relative expression of the OAS-TL3 gene in roots, stems, and leaves during the seedling, flowering, and bulking stages of the OAS-TL3 gene overexpression lines is higher than that of the recipient material. Compared to the recipient material JN74, the enzymatic activities, Cys, and GSH contents of OAS-TL are higher in the sulfur metabolic pathway of seedling roots. The receptor material JN74 is exogenously applied with different concentrations of reduced glutathione. The results demonstrate a positive correlation between reduced glutathione on total root length, projected area, surface area, root volume, total root tip number, total bifurcation number, and total crossing number. The Met and total protein contents of sulfur-containing amino acids in soybean seeds of the OAS-TL3 gene overexpression lines are higher than those of the recipient material JN74, while the gene-edited lines show the opposite results. In conclusion, the OAS-TL3 gene positively regulates soybean root growth, root activity, and the content of Met in the seeds through the OAS-TL-Cys-GSH pathway. It breaks the limitation of other amino acids and facilitates the increase of total seed protein content., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01348-y., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Melanocortin-3 receptor (MC3R) not only regulates energy homeostasis in animals, but also is an important regulator of inflammation. As one of the most widely farmed freshwater fish, common carp has attracted great interest for its feeding and inflammation regulation. In this study, we cloned the coding sequence (CDS) of common carp Mc3r (ccMc3r), examined its tissue expression profile, and investigated the function of this receptor in mediating downstream signaling pathways. The results showed that the CDS of ccMc3r was 975 bp, encoding a putative protein of 324 amino acids. Homology, phylogeny, and chromosomal synteny analyses revealed that ccMc3r is evolutionarily close to the orthologs of cyprinids. Quantitative real-time PCR (qPCR) indicated that ccMc3r was highly expressed in the brain and intestine. The luciferase reporter systems showed that four ligands, ACTH (1-24), α-MSH, β-MSH, and NDP-MSH, were able to activate the cAMP and MAPK/ERK signaling pathways downstream of ccMc3r with different potencies. For the cAMP signaling pathway, ACTH (1-24) had the highest activation potency; while for the MAPK/ERK signaling pathway, β-MSH had the greatest activation effect. In addition, we found that the four agonists were able to inhibit TNF-α-induced NF-κB signaling in approximately the same order of potency as cAMP signaling activation. This study may facilitate future studies on the role of Mc3r in common carp feed efficiency and immune regulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To explore the value of phase angle (PA) in constructing a predictive model of nutrition evaluation for tumor patients. Methods: A retrospective analysis was performed on 1 129 patients with malignant tumors hospitalized in the Cancer Center of Changzhi People's Hospital from June 2020 to February 2021. PA values of six parts of the body were measured by the body composition analyzer, including: left arm (LA), right arm (RA), left leg (LL), right leg (RL), the trunk (TR), and the whole body (WB). Patients' body mass index (BMI) was calculated and patient-generated subjective global assessment (PG-SGA) was assessed. The differences of PA values of six parts were compared and their correlations with BMI and PG-SGA in combination with age, gender and tumor disease types were analyzed, binary classification regression on BMI and PG-SGA was performed, and the functions of the best prediction model was fitted. Decision tree, random forest, Akaike information criterion in a Stepwise Algorithm (stepAIC) and generalized likelihood ratio test were used to select appropriate variables, and the logit logistic regression model was used to fit the data. Results: Comparing the PA values of six parts in pairs, it was found that the PA values of LA and RA, LL and RL, and TR and WB were linearly correlated and the coefficient was close to 1 ( P <0.001). Binary classification regression was performed for BMI and PG-SGA, respectively. In order to make the data have clinical significance, 18.5 kg/m(2) was used as the classification point for BMI, 4 and 9 were used as the classification points for PG-SGA score, and the models of A, B and C were obtained. Suitable variables including PA-LA, PA-TR and tumor disease types were used as variables to fit BMI classification; BMI, PA-LA and age were used as variables to fit the PG-SGA model with 9 as the classification point. PA-LA, PA-TR, BMI, age and tumor disease types were used as variables to fit the PG-SGA model with 4 as the classification point. In this study, the predicted values of models A, B and C obtained by R-studio were imported into SPSS 26.0 software, and the cut-off values of classification were obtained by the receiver operating characteristic (ROC) curve. The ROC analytic results showed that the best cut-off values of Model A, B and C were 0.155, 0.793 and 0.295. Model A recommended when the probability is >0.155, a patient's nutritiond tatus should be classified as BMI < 18.5 kg/m(2) group. Model B recommended that PG-SGA<9 group be classified as the probability is >0.793. Model C recommended that PG-SGA < 4 group should be classified when probability is >0.295. Conclusions: The PG-SGA classification prediction model is simple to operate, and the nutritional status of patients can be roughly divided into three groups: normal or suspected malnutrition group (PG-SGA<4), moderate malnutrition group (4≤PG-SGA<9), and severe malnutrition group (PG-SGA≥9). This model can more efficiently predict the nutritional status of cancer patients, greatly simplify the nutritional assessment process, and better guide the standardized treatment of clinical malnutrition.

Objectives: To study the clinical and gastroscopic features of children with cyclic vomiting syndrome., Methods: A retrospective analysis was performed on the medical data of 63 children with cyclic vomiting syndrome who were hospitalized and followed up in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University from August 2019 to March 2022., Results: Among the 63 children, there were 30 boys and 33 girls, with a mean age of 6.11 years, a mean course of disease of 2.57 years, and a mean vomiting period of 4.04 days. The most common accompanying symptom was listlessness or somnolence (55/63, 87%), followed by anorexia (45/63, 71%), abdominal pain or abdominal discomfort (40/63, 63%), constipation (19/63, 30%), salivation (12/63, 19%), nausea (11/63, 17%), headache (11/63, 17%), fever (6/63, 10%), and rash (1/63, 2%). All 63 children underwent gastroscopy, among whom 3 had no marked abnormalities, 22 (35%) had chronic superficial gastritis or chronic non-atrophic gastritis alone, and 38 (60%) had other abnormal changes aside from chronic gastritis (16 children with reflux esophagitis, 12 with bile reflux gastritis, 13 with duodenitis, 10 with erosive gastritis, and 5 with gastric or duodenal ulcer). Among the 63 children, 42 underwent pathological examinations of gastric mucosa, among whom 5 had no marked abnormalities, 34 had mild chronic gastritis, 2 had moderate chronic gastritis, and 1 had severe chronic gastritis. Among the 63 children, 15 received 24-hour dynamic esophageal pH monitoring during the interictal period, among whom 9 children were found to have pathological acid reflux., Conclusions: In addition to recurrent vomiting, most children with cyclic vomiting syndrome also have the symptoms such as somnolence or listlessness, anorexia, and abdominal pain. The main manifestation on gastroscopy is chronic gastritis, and most children may also have reflux esophagitis, bile reflux gastritis, and erosive gastritis. Mild chronic gastritis is the main pathological change of gastric mucosa.

Introduction: To investigate whether rescue in vitro maturation (R-IVM) improves the reproductive outcomes among women undergoing intracytoplasmic sperm injection (ICSI) after one oocyte retrieved cycle., Methods: Between January 2019 and December 2020, 2602 women who underwent ICSI in the Reproductive Medicine Center of Tongji Hospital, Wuhan, China, were included in our retrospective cohort study. There were 2112 women undergoing only ICSI and 490 women with R-IVM followed by ICSI. The intermediate reproductive outcomes and pregnancy outcomes were assessed, including the number of normally fertilized embryos, number of cleaved embryos, number of good-quality embryos, number of day-3 available embryos, number of embryos cultured past day-3, number of blastocysts, number of available blastocysts, biochemical pregnancy, miscarriage, clinical pregnancy and live birth. The perinatal outcomes were also assessed, including preterm birth and birth weight. The abovementioned outcomes were also calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group., Results: Compared with the women who underwent only ICSI, those who underwent ICSI with R-IVM had higher numbers of MII oocytes, normally fertilized embryos, cleaved embryos, day-3 available embryos, embryos cultured past day-3, and higher oocyte maturation rate, available embryo rate than women undergoing only ICSI. Additionally, we found that women undergoing ICSI with R-IVM had an increased chance of clinical pregnancy (adjusted OR=1.50, 95% CI: 1.17-1.93) and cumulative live birth (adjusted OR=1.35, 95% CI: 1.07-1.71). After propensity score matching (PSM), the cumulative live birth rate was 60.1% for women undergoing ICSI with R-IVM versus 54.9% for women undergoing only ICSI (OR=1.24, 95% CI: 0.94-1.63). The reproductive outcomes were also significantly different when calculated for in vivo matured and R-IVM oocytes separately in women undergoing ICSI with R-IVM group. All live births from R-IVM embryos were healthy and without malformations or complications., Conclusion: R-IVM may improve the reproductive outcomes of women undergoing ICSI. It may also provide a reference for the safety of R-IVM. This study maybe support a routine application of R-IVM among patients who intend to undergo ICSI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Jiang, Yao, Yao, Yuan, Wang, Deng, Du, Ren, Guo and Li.)

A 74-yr-old man underwent thoracic laparoscopy combined with radical gastrectomy, and the postoperative pathological diagnosis was esophageal and gastric cardia cancer pT3N1M0, pStage IIB. Immunohistochemical staining for HER2 (3+) and PD-L1 (<5%) was positive. Adjuvant chemotherapy was not performed because the patient developed severe thrombocytopenia (platelet counts <30 × 10 9 /L), which was never cured throughout the reporting period. At 10.7 months post-surgery, he suffered metastases in multiple organs, including the peritoneum, liver, lung, and bone. Following two cycles of first-line trastuzumab and pembrolizumab (200 mg), he developed immune-related myositis (G2), myocarditis (G2), and hepatitis (G1). Therefore, pembrolizumab was discontinued. Trastuzumab was administered as a monotherapy; meanwhile, adoptive cytokine-induced killer (CIK) cell infusions were initiated. Eight months after the initial immunotherapy, a solitary brain metastasis was detected, and the patient underwent CyberKnife radiosurgery. For second-line therapy, adoptive CIK cell immunotherapy plus trastuzumab was still used. At the time of reporting, the patient had achieved a complete response (CR) in the brain and liver and a partial response (PR) in the ilium, and he had been followed-up for 36.6 months, much longer than the median survival time for patients with advanced GEJ cancer. We suggest that HER2-targeted therapy and immunotherapy with pembrolizumab or CIK adoptive cell infusions prolonged the overall survival of an elderly patient with HER2-positive GEJ cancer with multiple metastases.

Pericardial fistula is a rare complication. Generally, the diagnosis can be confirmed by imaging examination, but our patient was an exception. We present a 71-year-old female patient that complained of remnant gastric cancer for five months and dyspnea for seven days; the dyspnea became aggravated during the last two days. After admission, emergency thoracic computed tomography and echocardiography showed pericardial effusion, and pericardiocentesis was performed. After conventional treatment, the pericardial effusion was unchanged and no cancer cells were found in the pericardial drainage. However, the color changed from turbid to golden yellow and, finally, to green. After 20 days of repeated laboratory, imaging, and gastrointestinal contrast examinations, no cause was found. Moreover, a clinical diagnosis could not be obtained following numerous comprehensive clinical analyses. Given the color change of the pericardial drainage, we strongly suspected pericardial fistula, but the imaging examinations were negative. Finally, a methylene blue test confirmed the existence of a pericardial fistula. When the color of the pericardial effusion changes, the existence of a pericardial fistula must be considered in advance, and other methods should be evaluated if imaging cannot assist in the diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the value of MRI diffusion tensor imaging (DTI) in the white matter changes of short-term methamphetamine (MA) abstinence. Methods: The data of DTI, demographics features, general information of addiction and impulsivity scale eleven (BIS-11) of 55 short-term MA addicts who were from Changsha, Zhuzhou and Yueyang compulsory detoxification centers in Hunan province, including 40 males and 15 females, aged 14-45 (37.24±7.31) years old, and 52 healthy controls, including 40 males and 12 females aged 18-59 (40.3±9.1) years were collected prospectively from August 2017 to December 2018. The differences of DTI indicators between the two groups were compared by tract-based spatial statistics (TBSS), and then the correlation between the different indicators and the age of first MA use, time of MA use, daily dose used, BIS-11 score were performed. Results: There were significant differences in BIS total score( P <0.001), BIS motivational impulsivity( P <0.001) and BIS attentional impulsivity( P =0.003) between MA group and healthy control group in short-term withdrawal. And compared with the healthy control group, the fractional anisotropy (FA) (0.58±0.02 vs 0.56±0.02,0.77±0.02 vs 0.75±0.04,0.79±0.04 vs 0.76±0.06; all P <0.05), axial diffusivity (AD) (0.57±0.01 vs 0.56±0.02, P =0.001) and mean diffusivity (MD) (0.66±0.02 vs 0.65±0.02,0.52±0.07 vs 0.51±0.06; both P <0.05)values in the MA group were all increased ( P <0.05), but there was no significant difference in the radial diffusivity (RD) value ( P >0.05). The white matter areas with increased FA value were located in the knee and body of corpus callosum, bilateral anterior corona radiata and left superior corona radiata; the areas with increased AD value were located in the knee, body and pressure of corpus callosum, bilateral anterior limb of internal capsule, posterior limb of internal capsule, anterior, superior and posterior corona radiata, external capsule and superior longitudinal fasciculus; and the areas with increased MD value were mainly located in the right superior longitudinal fasciculus, anterior and posterior limb of internal capsule. The corpus callosum, where there was a difference in FA between the two groups, was positively correlated with the daily dose of MA ( r =0.301, P =0.026). Conclusion: MA addicted individuals with short-term withdrawal have white matter edema and damage, and the degree of corpus callosum damage is positively correlated with the daily dose of MA,which is helpful to understand the pathophysiological process of white matter damage in the nervous system and the potential mechanism of neuropsychiatric symptoms in short-term withdrawal MA addicted individuals.