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Xiao-Yan Ren,1,* Meng-Ruo Xue,2,* Zhao-Li Yan,1 Shao-Jie Zhang,3 Min Liu,1 Ai-Zhen Li1 1Department of Endocrinology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People’s Republic of China; 2Department of Interventional Radiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, People’s Republic of China; 3Department of Anatomy, Inner Mongolia Medical University, Hohhot, 010050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhao-Li Yan, Department of Endocrinology, Affiliated Hospital of Inner Mongolia Medical University, No. 1, North Tongdao Street, Huiming District, Hohhot, 010050, People’s Republic of China, Tel +86 13848177245, Email yanzhaoliyzl9@126.comObjective: This study aimed to analyze the clinical characteristics and gene mutations of two families with maturity-onset diabetes of the young 3 (MODY 3) in Inner Mongolia.Methods: Fifty-three patients in Inner Mongolia suspected of having MODY 3 were enrolled in this study according to clinical manifestations. Blood samples were collected, and all exons of the HNF1α gene were analyzed; the second-generation DNA of the splicing regions of the gene was determined by direct sequencing.Results: In Family 1, the proband, mother, and uncle all carried the missense heterozygous mutation on exon 2 of the HNF1α gene (c.512G>A, p.Arg171Gln), and both the proband and uncle had MODY 3. In Family 2, the proband, grandfather, father, uncle I, and uncle II all carried a missense mutation on exon 2 (c.391C>t, p.Arg131Trp), and all had MODY 3. The blood glucose control in these patients was stable while they were being treated with oral sulfonylurea hypoglycemic drugs alone or with insulin. Uncle II had serious macrovascular and microvascular complications.Conclusion: Maturity-onset diabetes of the young 3 gene mutations (c.512G>A, p.Arg171Gln) and (c.391C>T, p.Arg131Trp) may be the main pathogenic genes of the two families with MODY 3. The two gene mutations found in this study have not been reported previously in China.Keywords: gene, HNF1α, MODY, c.512G>A, (Arg171Gln), c.391C>T, (Arg131Trp)

Wei Li,1,2,&ast; Nong Gao,2,&ast; Yi-Peng Pan,1 Xiu-Yun Ren2,3 1Department of Liver Transplantation, the Second Affiliated Hospital of Hainan Medical University, SanYa, People’s Republic of China; 2Department of Organ Transplantation, the Third Medical Center of General Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Ultrasound Examination, Hainan Hospital of General Hospital of People’s Liberation Army, SanYa, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Yun Ren, Department of Organ Transplantation, the Third Medical Center of General Hospital of People’s Liberation Army, Beijing, People’s Republic of China, Email rforestcloud@sina.comPurpose: This study aimed to investigate the application of color Doppler ultrasound (CDU) and contrast-enhanced ultrasound (CEU) in the early diagnosis of arterial steal syndrome (ASS) after orthotopic liver transplantation (OLT).Patients and Methods: A total of 1827 patients received OLT in our department between January 2007 and December 2021, and CDU and CEU were performed after surgery. Ultrasonographic data were collected and further analyzed. ASS was confirmed by digital subtraction angiography (DSA), and the use of splenic artery embolization was dependent on the DSA findings and clinical conditions. The ultrasonographic data were collected before and after embolization.Results: ASS was found in 23 patients (23/1827; 1.26%). CDU: the portal vein velocity was higher than normal in 17 patients (52.83± 21.74 cm/s); the hepatic artery flow signals disappeared in 7 patients; the hepatic artery velocity was 13.57± 5.85 cm/s in 16 patients. In 23 patients, the spleen artery velocity was 170.12± 32.04 cm/s. CEU: the hepatic artery was observed in 7 patients without hepatic artery flow signals on CDU; in 23 patients, the contrast agent reached the portal vein at the presence of contrast in the hepatic artery or earlier (difference: 2.21± 1.09 s). Splenic artery embolization was done in 17 of 23 patients with ASS. The hepatic artery flow velocity, hepatic artery resistance index, splenic artery velocity and time to the presence of contrast were significantly improved after embolization (P< 0.05).Conclusion: CDU and CEU are the preferred, effective tools in the diagnosis of ASS. Reduced peak hepatic artery velocity, increased spleen artery velocity and reduced time difference in the contrast reaching the portal vein and hepatic artery are indicative of ASS.Keywords: contrast-enhanced ultrasound, color Doppler ultrasound, liver transplantation, arterial steal syndrome

Hao-Ran Xu,1 Qian Yang,1 Shu-Yang Xiang,1 Pu-Hong Zhang,1 Yang Ye,1 Yan Chen,1 Ke-Wen Xu,2 Xi-Ya Ren,2 Hong-Xia Mei,1 Chen-Xi Shen,1 Hong-Yu Ma,1 Fang-Gao Smith,1,3 Sheng-Wei Jin,1 Qian Wang1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKCorrespondence: Sheng-Wei Jin; Qian WangDepartment of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaTel +86 577-88002806Fax +86 577-88832693Email jsw@wmu.edu.cn; wqian84@163.comBackground: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6– 8). Rosuvastatin (0.3 μmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h.Results: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway.Conclusion: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.Keywords: acute respiratory distress syndrome, rosuvastatin, alveolar fluid clearance, sodium channel, Na,K-ATPases

Xiaoli Li,1 Xiaoyong Ren,2 Jianmin Liang,2 Weijun Ma,2 Zhenghui Wang,2 Zhuangqun Yang3 1Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Plastic and Burns Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China Abstract: Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate immunoliposomes. Taken together, these results indicate that sodium morrhuate immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate immunoliposomes may represent a promising agent in the treatment of hemangiomas. Keywords: liposome, hemangioma, VEGF2, KDR, apoptosis

Background: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties., Purpose: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs., Study Design: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments., Methods: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations., Results: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes., Conclusion: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue., Competing Interests: Declaration of competing interest The authors have no financial interest or other potential conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4 + T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4 + subset polarization in a paracrine mode, in which TGFβ and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Smart optical materials with tunable fluorescence and room temperature phosphorescence (RTP) exhibit promising application prospects in the field of intelligent switches, information security, etc. Herein, a tetraimidazole derivative was grafted to one-dimensional lanthanum-diphosphonate through H-bonds, generating a coordination polymer (CP), (H 4 -TIBP)·[La 2 Li(H 2 -HEDP) 4 (H-HEDP)]·3H 2 O (termed La; TIBP = 3,3,5,5-tetra(imidazole-1-yl)-1,1-biphenyl; H 4 -HEDP = 1-hydroxyethylidene-1,1-diphosphonic acid) with a three-dimensional supramolecular structure. La shows dynamic fluorescence from blue to red and switchable monotonous yellowish-green RTP, which can be manipulated by reversible photochromism. It is worth noting that Eu 3+ /Tb 3+ -doped CPs exhibit time-resolved (red to yellow) and monotonous green afterglow, respectively, which can be attributed to multiple emissions with different decay rates. The dynamic and multicolor luminescence endows these CPs with potential for application in the domains of optical communications, multi-step encryption, and anti-counterfeiting. This work not only integrates color-adjustable fluorescence, switchable RTP, and photochromism in one material, but also realizes the manipulation of the resultant optical performances via photochromism, paving the pathway for the design and synthesis of smart optical materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Small extracellular vesicles (sEVs) have gained wide attention as efficient carriers for disease treatment. However, the proclivity of sEVs to be ingested by source cells is insufficient to accurately target specific sites, posing a challenge in realizing controlled targeting treatment. Here, we developed an engineered sEV nanocarrier capable of precise tumor targeting and enhanced synergistic therapy. Multivalent DNA probes, comprising abundant AS1411 aptamers and telomerase primers, were innovatively modified on the sEV membrane (M-D-sEV) for precise tumor targeting. To achieve synergistic therapy, gold nanorod-cerium oxide nanostructures (Au NRs-CeO 2 ) and manganese dioxide nanosheets-doxorubicin (MnO 2 NSs-DOX) were encapsulated into liposomes (Lip-Mat). Then M-D-sEV and Lip-Mat were fused together through membrane fusion to obtain nanocarriers. Owing to the multivalence of the probes, the surface of the nanocarriers was loaded with numerous aptamers, which greatly enhances their targeting ability and promotes the accumulation of drugs. When nanocarriers were ingested by tumor cells, telomerase and multivalent DNA probes triggered their aggregation, enhancing the therapeutic effect. Furthermore, under laser irradiation, Au NRs-CeO 2 converted light into hyperthermia, thereby inducing the destruction of nanocarriers membrane. This process initiated a series of reactions involving glutathione and H 2 O 2 consumption, as well as DOX release, ultimately achieving synergistic tumor therapy. In vitro and in vivo studies demonstrated the remarkable targeting ability of multivalent DNA probes and excellent therapeutic effect of this strategy. The engineered strategy of sEVs provide a promising approach for precise tumor therapy and hold great potential for the development of efficient, safe, and personalized drug delivery systems., 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 Inc. All rights reserved.)

Purpose: To investigate the safety and efficacy of radical radiotherapy for localized inoperable renal pelvic and ureteral carcinoma., Methods: 23 patients who received radiotherapy were enrolled. The prescribed dose was 60 to 67.5 Gy in 25 fractions and for bulky tumors, SABR was used in the first 3 to 5 times with tumor center boosted synchronously with 6 to 8 Gy/f. The Kaplan-Meier method was used to calculate local control (LC), DMFS, CSS and OS. Univariate analysis was performed by the log-rank test. The change in the eGFR before and after radiotherapy was compared by paired t test. The side effects were graded by CTCAE, version 5.0., Results: The median follow-up time was 17 months. The LC rates at 2 years after radiotherapy were 85.0%; the DMFS rates were 52.2%; the CSS rates were 83.0%; and the OS rates were 77.8%. The main failure mode after radiotherapy was distant metastasis. Univariate analysis revealed that T3-4 stage (P = .001), N+ status (P < .001) and a tumor volume ≥ 20 cc (P = .005) were poor prognostic factors for DMFS. There was no significant difference in the mean eGFR before and after radiotherapy (47.0 mL/min/1.73m 2 vs. 48.5 mL/min/1.73m 2 , P = .632). Only 1 patient developed acute grade 3 anemia. No patients developed grade 3 or higher late toxicities., Conclusion: For localized inoperable renal pelvic and ureteral carcinoma, radiotherapy is well tolerable with high local control and expected to bring survival benefits. In such patients, radiotherapy may be an option when surgery is unsuitable., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) show potential application in many domains, in which photochromic MOFs (PMOFs) have received enormous attention. Researchers mainly utilize photoactive ligands to build PMOFs. Recently, the mixed electron donating and accepting ligands strategies have also been used to construct PMOFs driven by the electron transfer between nonphotochromic moieties. However, the potential interligand competition inhibits the formation of PMOFs. Therefore, the exploration of single-ligand-guided assembly is conductive for building PMOFs. Considering the existing electron accepting and donating role of pyridyl and carboxyl, the pyridinecarboxyate derived from the fusion of pyridyl and carboxyl units may serve as single ligand to yield PMOFs (Figure 1d). In this work, the coordination assembly of bipyridinedicarboxylate (2,2'-bipyridine-4,4'-dicarboxylic acid, H 2 bpdc; 1,10-phenanthroline-2,9-dicarboxylic acid, H 2 pda) and LaCl 3 generate two PMOFs, [La(bpdc)(H 2 O)Cl] (1) and [La(pda)(H 2 O) 2 Cl]⋅2H 2 O (2). Both complexes feature dinuclear lanthanum as building blocks with differences in the connecting number of likers, in which 1 has (4,8)-connected topology and 2 exhibits sql topology. Their structural differences result in the diversities of photoresponsive functionalities. Compared with reported PMOFs built from photoactive ligands and mixed ligands, this study provides new available categories of single ligand for generating PMOFs and tuning the structure and photoresponsive properties via ligand substitution and external photostimulus., (© 2024 Wiley-VCH GmbH.)

Mucin 1 is an essential tumor biomarker, and developing cost-effective and portable methods for mucin 1 detection is crucial in resource-limited settings. Herein, the pH-regulated dual-enzyme mimic activities of manganese dioxide nanosheets were demonstrated, which were integrated into an aptasensor for dual-mode detection of mucin 1. Under acidic conditions, manganese dioxide nanosheets with oxidase mimic activities catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine sulfate, producing visible multicolor signals; while under basic conditions, manganese dioxide nanosheets with catalase mimic activities were used as catalyst for the decomposition of hydrogen peroxide, generating gas pressure signals. The proposed method allows the naked eye detection of mucin 1 through multicolor signal readout and the quantitative detection of mucin 1 with a handheld pressure meter or a UV-vis spectrophotometer. The study demonstrates that manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities can facilitate multidimensional transducing signals. The use of manganese dioxide nanosheets for the transduction of different signals avoids extra labels and simplifies the operation procedures. Besides, the signal readout mode can be selected according to the available detection instruments. Therefore, the use of manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities for dual-signal readout provides a new way for mucin 1 detection., 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.)

Background: Cancer immunotherapy provides durable response and improves survival in a subset of head and neck squamous cell carcinoma (HNSC) patients, which may due to discriminative tumor microenvironment (TME). Epigenetic regulations play critical roles in HNSC tumorigenesis, progression, and activation of functional immune cells. This study aims to identify an epigenetic signature as an immunophenotype indicator of durable clinical immunotherapeutic benefits in HNSC patients., Methods: Unsupervised consensus clustering approach was applied to distinguish immunophenotypes based on five immune signatures in The Cancer Genome Atlas (TCGA) HNSC cohort. Two immunophenotypes (immune 'Hot' and immune 'Cold') that had different TME features, diverse prognosis, and distinct DNA methylation patterns were recognized. Immunophenotype-related methylated signatures (IPMS) were identified by the least absolute shrinkage and selector operation algorithm. Additionally, the IPMS score by deconvolution algorithm was constructed as an immunophenotype classifier to predict clinical outcomes and immunotherapeutic response., Results: The 'Hot' HNSC immunophenotype had higher immunoactivity and better overall survival (p = 0.00055) compared to the 'Cold' tumors. The immunophenotypes had distinct DNA methylation patterns, which was closely associated with HNSC tumorigenesis and functional immune cell infiltration. 311 immunophenotype-related methylated CpG sites (IRMCs) was identified from TCGA-HNSC dataset. IPMS score model achieved a strong clinical predictive performance for classifying immunophenotypes. The area under the curve value (AUC) of the IPMS score model reached 85.9% and 89.8% in TCGA train and test datasets, respectively, and robustness was verified in five HNSC validation datasets. It was also validated as an immunophenotype classifier for predicting durable clinical benefits (DCB) in lung cancer patients who received anti-PD-1/PD-L1 immunotherapy (p = 0.017) and TCGA-SKCM patients who received distinct immunotherapy (p = 0.033)., Conclusions: This study systematically analyzed DNA methylation patterns in distinct immunophenotypes to identify IPMS with clinical prognostic potential for personalized epigenetic anticancer approaches in HNSC patients. The IPMS score model may serve as a reliable epigenome prognostic tool for clinical immunophenotyping to guide immunotherapeutic strategies in HNSC., (© 2024. Springer Nature Switzerland AG.)

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P <0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P= 0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Conversion from natural lands to cropland, primarily driven by agricultural expansion, could significantly alter soil microbiome worldwide; however, influences of forest-to-cropland conversion on microbial hierarchical interactions and ecosystem multifunctionality have not been fully understood. Here, we examined the effects of forest-to-cropland conversion on intratrophic and cross-trophic microbial interactions and soil ecosystem multifunctionality and further disclosed their underlying drivers at a national scale, using Illumina sequencing combined with high-throughput quantitative PCR techniques. The forest-to-cropland conversion significantly changed the structure of soil microbiome (including prokaryotic, fungal, and protistan communities) while it did not affect its alpha diversity. Both intrakingdom and interkingdom microbial networks revealed that the intratrophic and cross-trophic microbial interaction patterns generally tended to be more modular to resist environmental disturbance introduced from forest-to-cropland conversion, but this was insufficient for the cross-trophic interactions to maintain stability; hence, the protistan predation behaviors were still disturbed under such conversion. Moreover, key soil microbial clusters were declined during the forest-to-cropland conversion mainly because of the increased soil total phosphorus level, and this drove a great degradation of the ecosystem multifunctionality (by 207%) in cropland soils. Overall, these findings comprehensively implied the negative effects of forest-to-cropland conversion on the agroecosystem, from microbial hierarchical interactions to ecosystem multifunctionality.

Oligodendrocytes (OLs) are differentiated from oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). Demyelination is a common feature of many neurological diseases such as multiple sclerosis (MS) and leukodystrophies. Although spontaneous remyelination can happen after myelin injury, nevertheless, it is often insufficient and may lead to aggravated neurodegeneration and neurological disabilities. Our previous study has discovered that MEK/ERK pathway negatively regulates OPC-to-OL differentiation and remyelination in mouse models. To facilitate possible clinical evaluation, here we investigate several MEK inhibitors which have been approved by FDA for cancer therapies in both mouse and human OPC-to-OL differentiation systems. Trametinib, the first FDA approved MEK inhibitor, displays the best effect in stimulating OL generation in vitro among the four MEK inhibitors examined. Trametinib also significantly enhances remyelination in both MOG-induced EAE model and LPC-induced focal demyelination model. More exciting, trametinib facilitates the generation of MBP + OLs from human embryonic stem cells (ESCs)-derived OPCs. Mechanism study indicates that trametinib promotes OL generation by reducing E2F1 nuclear translocation and subsequent transcriptional activity. In summary, our studies indicate a similar inhibitory role of MEK/ERK in human and mouse OL generation. Targeting the MEK/ERK pathway might help to develop new therapies or repurpose existing drugs for demyelinating diseases., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects., 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 Wu, Yang, Huang, Fan, Dai, Hu, Tang, Liu, Xu, Liu, Cai, Niu, Ren, Yao, Qin, Chen, Huang, Zhang, You, Wang, He, Hong, Sun, Zhan and Lin.)

In view of the surgical complexity of parapharyngeal space tumors involved, this paper summarized the disease data of patients with parapharyngeal space tumors involved in the Department of Oral and Maxillofacial Surgery, the First Hospital of Shanxi Medical University from January 2015 to January 2021. It also summarized the surgical approach and mandibular management, so as to explore surgical strategies for different characteristics of parapharyngeal space tumors involved. A total of 49 patients, including 28 males and 21 females, median age 52 years (range 24-72 years). They were treated with four surgical approaches for tumor resection, 25 cervical approach, 5 cheek and neck approach, 3 transoral approach, and 16 cervical-maxillary approach. Among the patients treated with cervical-maxillary approach, 3 patients were treated with mandible square resection, and 6 patients were treated with temporary mandible dissection. Seven cases were treated with tumor resection and partial mandibular resection. There are various surgical approaches and mandibular management methods involving tumors in the parapharyngeal space, and clinical decisions should be made based on tumor diameter, location, boundary, blood supply and pathological types.

Arsenic (As) and cadmium (Cd) pose potential ecological threats to cropland soils; however, few studies have investigated their combined effects on multilevel organisms and soil functioning. Here, we used collembolans and soil microbiota as test organisms to examine their responses to soil As and Cd co-contamination at the gene, individual, and community levels, respectively, and further uncovered ecological relationships between pollutants, multilevel organisms, and soil functioning. At the gene level, collembolan transcriptome revealed that elevated As concentrations stimulated As-detoxifying genes AS3MT and GST, whereas the concurrent Cd restrained GST gene expression. At the individual level, collembolan reproduction was sensitive to pollutants while collembolan survival wasn't. At the community level, significant but inconsistent correlations were observed between the biodiversity of different soil keystone microbial clusters and soil As levels. Moreover, soil functioning related to nutrient (e.g., carbon, nitrogen, phosphorus, and sulfur) cycles was inhibited under As and Cd co-exposure only through the mediation of plant pathogens. Overall, these findings suggested multilevel bioindicators (i.e., AS3MT gene expression in collembolans, collembolan reproduction, and biodiversity of soil keystone microbial clusters) in cropland soils co-contaminated with As and Cd, thus improving the understanding of the ecotoxicological impact of heavy metal co-contamination on soil ecosystems., 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.)

Purpose: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes., Methods and Materials: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method., Results: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts., Conclusions: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system., Methods: Extracted proteins from 34 cerebrospinal fluid (CSF) samples [patients with MOGAD (MOG group, n = 12); healthy controls (HC group, n = 12); patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases (IND group, n = 10)] were processed and subjected to label-free quantitative proteomics. Supervised partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) models were also performed based on proteomics data. Functional analysis of differentially expressed proteins (DEPs) was performed using Gene Ontology, InterPro, and Kyoto Encyclopedia Genes and Genomes. An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD., Results: Four hundred and twenty-nine DEPs (149 upregulated and 280 downregulated proteins) were identified in the MOG group compared to the HC group according to the P value and fold change (FC). Using the O-PLS-DA model, 872 differentially abundant proteins were identified with variable importance projection (VIP) scores > 1. Five proteins (gamma-glutamyl hydrolase, cathepsin F, interalpha-trypsin inhibitor heavy chain 5, latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1) overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired. Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades, cell adhesion, axon guidance, and glycosphingolipid biosynthesis compared to the HC group., Conclusion: The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates., (© 2022. The Author(s).)

Solid proton electrolytes play a crucial role in various electrochemical energy storage and conversion devices. However, the development of fast proton conducting solid proton electrolytes at ambient conditions remains a significant challenge. In this study, a novel acidified nitrogen self-doped porous carbon material is presented that demonstrates exceptional superprotonic conduction for applications in solid-state proton battery. The material, designated as MSA@ZIF-8-C, is synthesized through the acidification of nitrogen-doped porous carbon, specifically by integrating methanesulfonic acid (MSA) into zeolitic imidazolate framework-derived nitrogen self-doped porous carbons (ZIF-8-C). This study reveals that MSA@ZIF-8-C achieves a record-high proton conductivity beyond 10 -2  S cm -1 at ambient condition, along with good long-term stability, positioning it as a cutting-edge alternative solid proton electrolyte to the default aqueous H 2 SO 4 electrolyte in proton batteries., (© 2023 Wiley-VCH GmbH.)

Purpose: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma., Methods: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878)., Conclusion: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the extent of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) damage in patients with idiopathic vocal cord paralysis (IVCP) exhibiting different paralytic sides., Methods: A total of 84 IVCP cases were evaluated using stroboscopic laryngoscopy, voice analysis, and laryngeal electromyography (LEMG). The results were compared between patients with left-sided paralysis and right-sided paralysis based on different disease courses (less than or more than 3 months)., Results: Initially, the average age and disease progression of IVCP patients were found to be similar regardless of the side of paralysis ( p  > .05). Additionally, there were no significant variations in voice indicators, such as MPT, DSI, and VHI, between IVCP patients with left and right vocal cord paralysis ( p  > .05). Furthermore, no disparities were detected in the latencies and amplitudes of the paralyzed RLN and SLN, as well as the durations and amplitudes of the action potentials in the paralyzed TM and PCM, among IVCP patients with left and right vocal cord paralysis ( p  > .05). Notably, the amplitudes of the left paralytic CM were significantly lower than those of the right paralytic CM (0.45 vs. 0.53, Z  = -2.013, p  = .044). In addition, no disparities were observed in APDs and amplitudes between the ipsilateral PCM and TM, either for patients with left or right vocal fold paralysis ( p  > .05). Finally, all the IVCP patients were subdivided into two subgroups according to different disease course (less than or more than 3 months), and in each subgroup, the comparison of voice indicators and LEMG results in IVCP patients with left or right vocal fold paralysis were similar with the above findings ( p  > .05)., Conclusion: Overall, the degree of RLN and SLN damage appeared to be similar in IVCP patients with left and right vocal cord paralysis, provided that the disease course was comparable., Level of Evidence: 4., Competing Interests: All authors have no conflict of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAF V600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAF V600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAF V600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age( t =1.444, P =0.151),gender( χ 2 =0.259, P =0.611),and location of nodules( χ 2 =2.055, P =0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size( Z =2.500, P =0.012),echo( χ 2 =14.693, P <0.001),composition( χ 2 =17.075, P <0.001),aspect ratio ≥1( χ 2 =9.477, P =0.002),and microcalcification( χ 2 =6.892, P =0.009)were of significance for the differentiation.When applied alone,BRAF V600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity( χ 2 =37.923, P <0.001; χ 2 =40.462, P <0.001)and accuracy( χ 2 =81.595, P <0.001; χ 2 =76.912, P <0.001),while C-TIRADS had the highest specificity( χ 2 =11.746, P <0.001; χ 2 =21.235, P <0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone( Z =1.177, P =0.239; Z =0.213, P =0.831; Z =1.016, P =0.310).The combination of BRAF V600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAF V600E mutation in distinguishing the benign and malignant AUS/FLUS nodules( Z =2.107, P =0.035; Z =2.752, P =0.006).The combination of ATA guidelines with BRAF V600E mutation increased the diagnostic accuracy of BRAF V600E mutation( χ 2 =20.679, P <0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules( Z =1.321, P =0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAF V600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules( Z =2.770, P =0.006; Z =2.770, P =0.006; Z =2.890, P =0.004).Specifically,ACR-TIRADS combined with BRAF V600E mutation showed the highest sensitivity( χ 2 =4.712, P =0.030; χ 2 =4.712, P =0.030),while C-TIRADS combined with BRAF V600E mutation showed the highest accuracy( χ 2 =77.627, P <0.001; χ 2 =85.827, P <0.001).However,there were no statistically significant differences in diagnostic performance between the combinations( Z =1.276, P =0.202; Z =0.808, P =0.419; Z =1.615, P =0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAF V600E mutation can improve the diagnostic efficacy of BRAF V600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

An elegant Lewis acid catalyzed, protection-free, and straightforward synthetic strategy for the assembly of a series of sophisticated polycyclic quinoline skeletons employing propargylic alcohols and 2-vinylanilines as the substrates in the presence of Yb(OTf) 3 (10 mol %) and AgOTf (10 mol %) in tetrahydrofuran has been described. This annulation protocol, which proceeds through a sequential Meyer-Schuster rearrangement/nucleophilic substitution/deprotonation sequence, provides a versatile, practical, and atom-economical approach for accessing quinoline derivatives in moderate-to-good yields.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system., 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.)

Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management.

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

Parasitoid wasps are a diverse group of hymenopteran insects that serve as invaluable resources for pest biocontrol. To ensure successful parasitism, parasitoid wasps inject venom into their hosts to suppress their hosts' immunity, modulate hosts' development, metabolism, and even behavior. With over 600,000 estimated species, the diversity of parasitoid wasps surpasses that of other venomous animals, such as snakes, cone snails, and spiders. Parasitoid wasp venom is an underexplored source of bioactive molecules with potential applications in pest control and medicine. However, collecting parasitoid venom is challenging due to the inability to use direct or electrical stimulation and the difficulty in dissection because of their small size. Trichogramma is a genus of tiny (~0.5 mm) egg parasitoid wasps that are widely used for the biological control of lepidopteran pests in both agriculture and forests. Here, we report a method for extracting venom from T. dendrolimi using artificial hosts. These artificial hosts are created with polyethylene film and amino acid solutions and then inoculated with Trichogramma wasps for parasitism. The venom was subsequently collected and concentrated. This method enables the extraction of large amounts of Trichogramma venom while avoiding contamination from other tissues caused by dissection, a common issue in venom reservoir dissection protocols. This innovative approach facilitates the study of Trichogramma venom, paving the way for new research and potential applications.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts., (© 2023. People´s Military Medical Press.)

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The number of diabetic patients visiting stomatology for periodontal disease is increasing, and the symptoms are relatively severe, and often complications increase the complexity of periodontal treatment. This article briefly describes the research progress and clinical manifestations of the epidemiology and related pathological mechanisms of periodontitis with diabetes, focusing on the treatment and providing reference for stomatologists in the clinical diagnosis and treatment of patients with diabetic periodontitis.

Photochromic metal-organic complexes (PMOCs) have received huge attention of chemists, thanks to their diverse structural characteristic and various available photo-modulate physicochemical functionalities. The organic ligand plays a crucial role in the quest of PMOCs with specific photo-responsive functionalities. The multiple coordination modes of polydentate ligands also provide possibilities for forming isomeric MOCs, which may open a new perspective on the research of PMOCs. The exploration of suitable PMOC systems is significant for the yield of isomeric PMOCs. Taking into account extant PMOCs based on polypyridines and carboxylate as electron acceptors (EAs) and donors (EDs), the covalent fusion of suitable pyridyl and carboxyl species may produce single functionalized ligands bearing ED and EA moieties for the building of novel PMOCs. In this study, the coordination assembly of bipyridinedicarboxylate (2,2'-bipyridine-4,4'-dicarboxylic acid, H 2 bpdc) and Pb 2+ ions generate two isomeric MOCs, [Pb(bpdc)]·H 2 O ( 1 and 2 ), which have the same chemical compositions with main discrepancies in the coordination mode of bpdc 2- ligands. As expected, supramolecular isomers 1 and 2 exhibited different photochromic performance, thanks to the distinct microscopic functional structural units. A schematic encryption and anti-counterfeiting device based on complexes 1 and 2 has also been studied. Compared with the extensively studied PMOCs supported by photoactive ligands like pyridinium and naphthalimide-derivatives and PMOCs derived from mixed electron-accepting polydentate N-ligands and electron-donating ligands, our work provides a new idea for building PMOCs based on pyridinecarboxylic acid ligands.

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial-mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.

Objective: To explore the correlation between ultrasound images and molecular typing of invasive breast cancer, so as to analyze the predictive value of preoperative ultrasound for invasive breast cancer., Methods: 302 invasive breast cancer patients were enrolled in Heping Hospital affiliated to Changzhi Medical College in Shanxi, China during 2020 to 2022. All patients accepted ultrasonic and pathological examination, and all pathological tissues received molecular typing with immunohistochemical (IHC) staining. The relevance between different molecular typings and ultrasonic image, pathology were evaluated., Results: Univariate analysis: among the four molecular typings, there were significant differences in tumor size, shape, margin, lymph node and histological grade ( P <0.05). 1. Size: Luminal A tumor was smaller (69.4%), Basal -like type tumors are mostly larger (60.9%); 2. Shape: Basal-like type is more likely to show regular shape (45.7%); 3. Margin: Luminal A and Luminal B mostly are not circumscribed (79.6%, 74.8%), Basal -like type shows circumscribed(52.2%); 4. Lymph nodes: Luminal A type tends to be normal (87.8%), Luminal B type,Her-2+ type and Basal-like type tend to be abnormal (35.6%,36.4% and 39.1%). There was no significant difference in mass orientation, echo pattern, rear echo and calcification ( P >0.05). Multivariate analysis: Basal-like breast cancer mostly showed regular shape, circumscribed margin and abnormal lymph nodes ( P <0.05)., Conclusion: There are differences in the ultrasound manifestations of different molecular typings of breast cancer, and ultrasound features can be used as a potential imaging index to provide important information for the precise diagnosis and treatment of breast cancer., 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 Pan, Zhang, Yan, Jia, Ren, Wu, Hao and Li.)

Objective: The aim of this study was to assess the effect of flap design for impacted mandibular third molar extraction on the distal periodontal tissue of their neighbors clinically, immunologically, and microbiologically., Study Design: This randomized controlled study comprised 100 patients who were allocated randomly to receive either a triangular flap or a modified triangular flap. The distal periodontal pocket depth, plaque index, bleeding on probing, the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and the level of interleukin-1β, interleukin-8 and matrix metalloproteinase-8 of adjacent second molars were measured at baseline, and 1, 4 and 8 weeks after surgery., Results: After 1 and 4 weeks, distal periodontal conditions of adjacent second molars deteriorated, along with an increase in subgingival microbiota and inflammatory factors in both groups. And compared to the modified triangular flap group, the triangular flap group significantly increased ( p  < 0.05). Prevotella intermedia, interleukin-1β and probing depth were positively correlated in both groups. After 8 weeks, they returned to the preoperative level., Conclusions: In this study, both flap designs for impacted mandibular third molar extractions was associated with worse clinical periodontal indices, increased inflammatory biomarkers of gingival crevicular fluid, and more subgingival pathogenic microbiota within 4 weeks. But compared with the triangular flap, the modified triangular flap was better for distal periodontal health of adjacent second molars, which provides certain directions for clinical treatment., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Objective: This study aimed to analyze the characteristics of laryngopharyngeal reflux (LPR) by using narrow band imaging (NBI) endoscopy., Study Design: A prospective study., Setting: A large-volume practice with tertiary care providers., Methods: A total of 67 patients with suspected LPR who underwent 24-hour multichannel intraluminal impedance-pH monitoring were included from June 2020 to March 2022. Manifestations of NBI endoscopy included submucosal clustered brownish microvessels (CBMs), spotted brownish microvessels, and no special microvessels; the latter 2 formed the non-CBM group. The manifestations of all patients and their changes were observed after 8 weeks of proton pump inhibitor and symptomatic treatment for patients with LPR, and symptomatic treatment for patients without LPR., Results: According to the results of 24-hour multichannel intraluminal impedance-pH monitoring, the incidence of submucosal CBMs was significantly higher in patients with LPR (30 cases) than in those without LPR (37 cases, P < .001), particularly in the posterior cricoid area (P < .001). Besides Reflux Finding Score, the incidence of signs such as subglottic edema and vocal fold edema was significantly higher in the CBM group than the non-CBM group (P < .05). Finally, 22 patients with LPR (91.7%) and only 2 patients without LPR (28.6%) underwent a transformation from CBMs to spotted brownish microvessels after continuous medication for 8 weeks in the CBM group (χ 2 = 15.916, P < .001), while no significant change was observed in patients with or without LPR in the non-CBM group (P > .05)., Conclusion: Submucosal CBMs in the posterior cricoid area under NBI endoscopy may be a characteristic of LPR., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Prior studies indicated the involvement of neuroinflammation in the dopaminergic neurodegeneration in mice of paraquat (PQ)-induced Parkinson's disease (PD), but the underlying mechanisms remain to be elucidated. The present study explored whether microglia-mediated inflammation disrupted blood-brain barrier (BBB) and its related mechanism. C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks, following with or without minocycline (intraperitoneal injection, once every two days). The microglial activation, BBB permeability, expression of tight junctions (TJs) proteins and matrix metalloproteinase (MMP), as well as the loss of dopaminergic neurons and neurological deficits assessment, were evaluated. Minocycline efficiently restrained nigral microglial activation induced by PQ in mice. PQ-induced increase of EB content in the brain and excessive expression of zonula occludin-1 (ZO-1), claudin-5 and occludin were significantly dampened by minocycline treatment. Inhibition of microglial activation by minocycline greatly ameliorated the loss of dopaminergic neurons and neurological dysfunctions in PQ-exposed mice. Also, microglial inactivation downregulated the expression of MMP-2/9 in PQ-lesioned mice. These findings suggested the potential protection of suppressing microglia-mediated neuroinflammation against dopaminergic neurodegeneration through attenuating BBB disruption in a mouse of PQ-induced PD, and MMP-2/9 might involve in the contribution, which needs to be verified in future study., 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 Elsevier Ltd. All rights reserved.)

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF- α , IL-1 β , PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Yi-li Wang et al.)

Background: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML., Methods: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experi-ments on leukemia cell lines and primary leukemia blasts were performed in vitro., Results: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro., Conclusions: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs.

Background: Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct., Methods: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2 -/- mice were used to test the effect and mechanism of YWP against CLD., Results: The network analysis identified nine main active ingredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, gederagenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, inflammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2 -/- mice. The mechanism exploration showed that YWP mainly decreased inflammatory response by inhibiting AKT/P38MAPK signaling., Conclusion: This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2 -/- mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling., 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. Published by Elsevier B.V.)

The fall armyworm (FAW) Spodoptera frugiperda is a destructive and polyphagous pest of many essential food crops including maize and rice. The FAW is hard to manage, control, or eradicate, due to its polyphagous nature and voracity of feeding. Here, we report the characterization and functional analysis of the detoxification gene CYP302A1 and how S. frugieprda larvae use a detoxification mechanism to adapt host plants. Results demonstrated that CYP302A1 expression levels were much higher in midgut tissue and the older S. frugiperda larvae. Our current studies revealed the enhanced P450 activity in the midguts of S. frugiperda larvae after exposure to rice plants as compared to corn plants and an artificial diet. Furthermore, higher mortality was observed in PBO treated larvae followed by the exposure of rice plants as compared to the corn plant. The dsRNA-fed larvae showed downregulation of CYP302A1 gene in the midgut. At the same time, higher mortality, reduced larval weight and shorter developmental time was observed in the dsRNA-fed larvae followed by the exposure of rice plant as compared to the corn plant and DEPC-water treated plants as a control. These results concluded that the inducible P450 enzyme system and related genes could provide herbivores with an ecological opportunity to adapt to diverse host plants by utilizing secondary compounds present in their host plants., 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 Hafeez, Li, Chen, Ullah, Huang, Zhang, Zhang, Siddiqui, Zhou, Ren, Imran, Assiri, Lou and Lu.)

Optimized source-sink interactions are determinants of both rice yield and quality. However, most source genes have not been well studied in rice, a major grain crop. In this study, OsBMY4 and OsISA3, the key β-amylase and debranching enzymes that control transient starch degradation in rice leaves, were co-overexpressed in rice in order to accelerate starch degradation efficiency and increase the sugar supply for sink organs. Systematic analyses of the transgenic rice indicated that co-overexpression of OsBMY4 and OsISA3 not only promoted rice yield and quality, but also improved seed germination and stress tolerance. Moreover, since the OsBMY4 gene has not been characterized, we generated osbmy4 mutants using CRIPSR/Cas9 gene editing, which helped to reveal the roles of β-amylase in rice yield and quality. This study demonstrated that specific modulation of the expression of some key source genes improves the source-sink balance and leads to improvements in multiple key traits of rice seeds.