Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

Objective To investigate the current situation of personnel training,material alloca-tion,process implementation and quality monitoring of gastrointestinal endoscopy cleaning and disin-fection in medical institutions at all levels in Yangzhou City,so as to provide reliable data for further improving the quality management of digestive endoscopy cleaning and disinfection in the city.Meth-ods According to the latest industry standards,a questionnaire was designed to carry out an online questionnaire survey on the status quo of digestive endoscopy cleaning and disinfection in 74 medical institutions of different levels in Yangzhou City,and the results were analyzed.Results 50％of the city's hospitals adopt the way of self-training within the department,and only 22 people have obtained the provincial or above professional cleaning and disinfection certificate.In 21.62％of hospitals,cleaning and disinfection personnel were not assessed before starting work.13.51％of the hospitals did not use purified water for terminal rinsing,and 44.59％of the hospitals did not have a cleaning and disinfection machine.79.73％of hospitals recorded by hand.71.62％of the hospitals failed to carry out standard cleaning quality monitoring,83.78％of the hospitals did not implement biofiltra-tion monitoring method.In addition,in the biological monitoring in 2023,14.86％of hospitals had the problem of excessive microorganisms.Conclusion The implementation of endoscope cleaning and disinfection standards varied significantly among medical institutions in Yangzhou,with level one and level two hospitals posing potential hospital infection risks.It is recommended to establish a pro-fessional entry system for endoscope cleaning and disinfection personnel citywide,increase investment in hardware facilities,and strictly enforce monitoring standards.

Objective To explore the application value of metagenomic next-generation sequen-cing(mNGS)technology in the diagnosis of spinal tuberculosis.Methods A total of 129 patients with suspected spinal tuberculosis admitted from January 2021 to January 2023 were selected as study subjects.Lesion tissue samples were collected intraoperatively and subjected to conventional microbio-logical testing(CMT),Mycobacterium tuberculosis DNA(MTB-DNA)amplification testing,and mNGS testing.The diagnostic efficacy of different testing methods was compared using results of com-prehensive clinical diagnosis as the gold standard.Results Among 129 patients,101(78.29％)were confirmed to have spinal tuberculosis,and 28(21.71％)had other spinal infections.Using clinical results as the diagnostic gold standard,the sensitivity of mNGS was 94.06％(95/101),and specificity was 89.29％(25/28);the sensitivity of MTB-DNA amplification was 90.10％(91/101),and specificity was 89.29％(25/28);the sensitivity of CMT was 86.14％(87/101),and specifici-ty was 85.71％(24/28).Compared with MTB-DNA amplification and CMT,mNGS showed the highest consistency with clinical results,and its consistency in detecting different lesion sites was also optimal,with statistically significant differences(P＜0.05).Conclusion mNGS testing has high diagnostic value for spinal tuberculosis and can provide a reference for clinical diagnosis,thereby guiding clinical decision-making.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To explore the predictive value of early serum tumor markers (STM) , neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) combination score on the efficacy of gastric cancer immunotherapy.Methods:A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1, 2020 to June 30, 2022 were selected. Patients' leading STM, NLR, PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic (ROC) curve. The clinical efficacy and prognosis of different leading STM, NLR, PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival.Results:The best truncation value for NLR was 2.75, and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy, the objective response rate (ORR) was 23.7% (18/76) , and the disease control rate (DCR) was 88.2% (67/76) . There were no significant differences in ORR [ (20.9% (9/43) vs. 27.3% (9/33) ], DCR [83.7% (36/43) vs. 93.9% (31/33) ] between the high NLR group ( n=43) and low NLR group ( n=33) ( χ2=0.42, P=0.519; χ2=1.02, P=0.313) . There were no significant differences in ORR [27.3% (12/44) vs. 18.8% (6/32) ], DCR [81.8% (36/44) vs. 96.9% (31/32) ] between the high PLR group ( n=44) and low PLR group ( n=32) ( χ2=0.75, P=0.388; χ2=2.71, P=0.555) . The ORR for the high combined score group ( n=39) and low combined score group ( n=37) was 17.9% (7/39) and 29.7% (11/37) , respectively, with no statistically significant difference ( χ2=1.46, P=0.230) ; the DCR was 79.5% (31/39) and 97.3% (36/37) , respectively, with a statistically significant difference ( χ2=4.19, P=0.041) . The median progression free survival (PFS) and overall survival (OS) of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=7.95, P=0.005) ; the median OS was 12.0 and 14.0 months, respectively, with no statistically significant difference ( χ2=1.04, P=0.307) . The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=3.90, P=0.048) ; the median OS was 13.0 and 13.0 months, respectively, with no significant difference ( χ2=0.02, P=0.896) . The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=13.52, P<0.001) ; the median OS was 12.0 and 14.0 months, respectively, with a statistically significant difference ( χ2=5.02, P=0.025) . ROC curve analysis showed that the area under curve (AUC) of leading STM, NLR, PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662, 0.697, 0.601 and 0.773. Univariate analysis showed that, surgery ( HR=0.59, 95% CI: 0.36-0.95, P=0.031) , leading STM ( HR=0.57, 95% CI: 0.34-0.93, P=0.026) , NLR ( HR=0.54, 95% CI: 0.34-0.87, P=0.011) , combined score ( HR=0.42, 95% CI: 0.26-0.68, P<0.001) were all influencing factors for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.30, 95% CI: 0.12-0.75, P=0.011) , leading STM ( HR=0.28, 95% CI: 0.15-0.50, P<0.001) , combined score ( HR=0.55, 95% CI: 0.31-0.96, P=0.036) were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that, leading STM ( HR=0.56, 95% CI: 0.33-0.98, P=0.041) was an independent influencing factor for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.29, 95% CI: 0.11-0.76, P=0.012) , leading STM ( HR=0.32, 95% CI: 0.17-0.58, P<0.001) , combined score ( HR=0.46, 95% CI: 0.25-0.82, P=0.009) were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion:The combined score of leading STM, NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer, and can predict the efficacy of immunotherapy for gastric cancer.

Objective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.