A case of delayed recurrent hyphema following Implantable Collamer Lens (ICL) surgery.

Purpose: To present a case of delayed recurrent hyphema following toric ICL implantation. Observations: This case reports a 24-year-old Asian female who presented with sudden decrease in vision in the right eye, accompanied by recurrent massive anterior chamber hemorrhage, six months after bilateral implantation of toric ICL with central holes for myopia correction. Despite initial conservative treatment with immobilization and intraocular pressure (IOP)-lowering medication at another hospital, the hyphema persisted. At our hospital, her corrected visual acuity (CDVA) in the right eye was counting fingers (CF) at 50 cm, with visible blood clots and hyphema in the anterior chamber, and an IOP of 40 mmHg. Ultrabiomicroscopy (UBM) indicated a large amount of hyphema in the anterior chamber. Initially, the patient was treated with a combination of three IOP-lowering medications: brimonidine eye drops, brinzolamide eye drops, and timolol eye drops, but the condition recurred. Two weeks later, we performed an anterior chamber hyphema evacuation and ICL removal surgery in the right eye. Postoperatively, the patient's IOP stabilized and her vision gradually recovered. One month after the surgery, a follow-up examination showed a CDVA of LogMAR 0.6 in the affected eye. Conclusion and importance: This case report is essential for characterizing a rare and serious complication following toric ICL implantation, highlighting the importance of close monitoring and timely intervention.

The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.

The epithelial-mesenchymal transition (EMT) is a critical tumor invasion and metastasis process. EMT enables tumor cells to migrate, detach from their original location, enter the circulation, circulate within it, and eventually exit from blood arteries to colonize in foreign sites, leading to the development of overt metastases, ultimately resulting in death. EMT is intimately tied to stromal cells around the tumor and is controlled by a range of cytokines secreted by stromal cells. This review summarizes recent research on stromal cell-mediated EMT in tumor invasion and metastasis. We also discuss the effects of various stromal cells on EMT induction and focus on the molecular mechanisms by which several significant stromal cells convert from foes to friends of cancer cells to fuel EMT processes via their secretions in the tumor microenvironment (TME). As a result, a better knowledge of the role of stromal cells in cancer cells' EMT may pave the path to cancer eradication.

MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.

PURPOSE: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND METHODS: In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND CONCLUSIONS: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

A novel non-linear approach for establishing a QSAR model of a class of 2-Phenyl-3-(pyridin-2-yl) thiazolidin-4-one derivatives.

In this investigation, we aimed to address the pressing challenge of treating osteosarcoma, a prevalent and difficult-to-treat form of cancer. To achieve this, we developed a quantitative structure-activity relationship (QSAR) model focused on a specific class of compounds called 2-Phenyl-3-(pyridin-2-yl) thiazolidin-4-one derivatives. A set of 39 compounds was thoroughly examined, with 31 compounds assigned to the training set and 8 compounds allocated to the test set randomly. The goal was to predict the IC50 value of these compounds accurately. To optimize the compounds and construct predictive models, we employed a heuristic method of the CODESSA program. In addition to a linear model using four carefully selected descriptors, we also developed a nonlinear model using the gene expression programming method. The heuristic method resulted in correlation coefficients (R 2) of 0.603, 0.482, and 0.107 for R2 cv and S2, respectively. On the other hand, the gene expression programming method achieved higher R 2 and S2 values of 0.839 and 0.037 in the training set, and 0.760 and 0.157 in the test set, respectively. Both methods demonstrated excellent predictive performance, but the gene expression programming method exhibited greater consistency with experimental values. The successful nonlinear model generated through gene expression programming shows promising potential for designing targeted drugs to combat osteosarcoma effectively. This approach offers a valuable tool for optimizing compound selection and guiding future drug discovery efforts in the battle against osteosarcoma.

[Pulmonary Mucinous Adenocarcinoma Combined with Bronchial Squamous Cell 
Papilloma and Infection with Tropheryma Whipplei: A Case Report].

Simultaneous multiple primary tumors on the same side of the lung with Tropheryma whipplei (TW) infection are rare. We reviewed the clinical data, imaging manifestations, pathological results, diagnosis and treatment of a primary pulmonary mucinous adenocarcinoma (PPMA) patient with bronchial squamous cell papilloma (BSCP) and TW infection, and discussed our treatment experience. The patient mainly presented with chronic cough and sputum, and computed tomography (CT) showed inflammatory changes with multiple nodular shadows. Biopsy of the lower lobe of the right lung showed PPMA, and right lung sub-branchial nodules discovered during bronchoscope revealed BSCP. Metagenomics next generation sequencing (mNGS) of bronchoalveolar lavage fluid showed mixed infection of Streptococcus pneumoniae and TW with a poor anti-infective effect. No clear genetic mutation was detected, and the patient was treated with chemotherapy and regularly followed up. We should improve the awareness of multiple pulmonary pathologies during clinical practice, avoid missed diagnosis and misdiagnosis, and carry out comprehensive treatment after clarifying the diagnosis as soon as possible.
.

Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population.

BACKGROUND: The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population. METHODS: A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3-4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients. RESULTS: At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89. CONCLUSIONS: The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.

Risk factors for advanced colorectal neoplasm in young adults: a meta-analysis.

Purpose: To evaluate the risk factors for young-onset advanced colorectal neoplasia. Methods: We performed a meta-analysis of 30 potential exposure risk factors from 28 original studies. Results: Several risk factors showed statistical significance, including male sex (odds ratio [OR]: 1.28; 95% CI: 1.12-1.47), metabolic syndrome (OR: 1.34; 95% CI: 1.25-1.44), hypertension (OR: 1.22; 95% CI: 1.17-1.28), diabetes (OR: 1.23; 95% CI: 1.15-1.32), inflammatory bowel disease (OR: 4.62; 95% CI: 1.12-17.54), obesity (OR: 1.23; 95% CI: 1.06-1.43), sedentary behavior (OR: 1.25; 95% CI: 1.06-1.48), smoking (OR: 1.19; 95% CI: 1.05-1.36), high alcohol consumption (OR: 1.37; 95% CI: 1.10-1.71), high intake of sugar (OR: 2.58; 95% CI: 1.61-4.13) and red meat (OR: 1.10; 95% CI: 1.04-1.16) and family history of colorectal cancer (OR: 3.14; 95% CI: 1.29-7.64). Conclusion: Our study identified potential risk factors for young-onset advanced colorectal neoplasms to help develop targeted primary prevention strategies.

Bibliometric analysis of global research on physical activity and sedentary behavior in the context of cancer.

Objective: Numerous studies focusing on sedentary behavior (SB) and physical activity (PA) in the context of cancer have been reported in recent years. We analyzed and visualized studies on SB and PA in patients with cancer over the last 20 years using scientometric methods, to provide insights on gaps and deficiencies in the literature, and to inform future research guidelines. Methods: All relevant studies in the field from 2001 to October 2022 were reviewed using bibliometric tools, including VOSviewer, Bibliometric online analysis platform, and biblioshiny, to determine the most influential countries, institutions, journals, and authors. We explored current research hotpots and potential research trends, based on keyword clustering and dynamic changes. Our research focuses on PA, SB, and cancer across the entire cancer continuum, from primary prevention to treatment to cancer survivorship. Results: Scientometric analysis identified 4,382 relevant manuscripts on SB and PA in the context of cancer, with a 10-fold increase in articles over the past 20 years. The United States, Canada, and Australia were the most influential countries. The journal, Supportive Care in Cancer, had the highest number of publications, while Clinical Oncology had the highest H-index. K.S. Courneya was the most influential author in this field, with the highest number of publications, total citations, and H-index. Keyword analysis revealed that current research is focused on PA and SB in patients with breast cancer, quality of life, and aerobic exercise. Future frontiers include cancer prehabilitation programs and cardiorespiratory fitness, and remote intervention and social support. Conclusion: By using bibliometrics, we conducted a comprehensive review of SB and PA in cancer-related studies. The current research focused on exercise and sedentariness in breast cancer patients and the role of PA in improving quality of life in survivorship. Emerging research foci were generally around cancer prehabilitation programs and remote intervention issues for PA. In addition, some publication deficits are noted: studies of PA and SB in less common cancers; the recommended doses and intensities of exercise for cancer; the timing of interventions for prehabilitation and the establishment of individualized exercise protocols. These deficiencies align with the needs for future research topics.

Electro-acupuncture treatment inhibits the inflammatory response by regulating γδ T and Treg cells in ischemic stroke.

BACKGROUND: Electro-acupuncture (EA) is an effective and safe treatment for ischemic stroke. It is not only capable of reducing cerebral damage but also alleviating intestinal inflammation. However, its mechanism has not been fully elucidated. METHODS: All rats were randomly divided into three experimental groups: the SHAM group, the MCAO group, and the MEA (MCAO+EA) group. Ischemic-reperfusion (I/R) injury was induced by MCAO surgery. Rats in the MEA group were treated with EA stimulation in the "Baihui" acupoint (1 mA, 2/15 Hz, 20 min for each time). The Real-time (RT)-qPCR was used to evaluate the mRNA expression of inflammation factors in the ischemic brain and the small intestine after I/R injury. In addition, our research evaluated the effects of EA on regulatory T cells (Tregs) and γδ T cells in the small intestine and brain via Flow cytometry analysis. Finally, we applied CM-Dil and CFSE injection and explored the potential connections of T cells between the ischemic hemisphere and the small intestine. RESULTS: Our results suggested that EA treatment could significantly reduce the inflammation response in the ischemic brain and small intestine 3 days after I/R injury in rats. To be specific, EA increased the percentage of Tregs in the brain and the small intestine and decreased intestinal and cerebral γδ T cells. Concomitantly, after EA treatment, the percentage of cerebral CD3+TCRγδ+CFSE+ cells dropped from 12.06% to 6.52% compared with the MCAO group. CONCLUSIONS: These findings revealed that EA could regulate the Tregs and γδ T cells in the ischemic brain and the small intestine, which indicated its effect on inhibiting inflammation. And, EA could inhibit the mobilization of intestinal T cells, which may contribute to the protection of EA after ischemic stroke.

Selection of rice and maize varieties with low cadmium accumulation and derivation of soil environmental thresholds in karst.

Cadmium (Cd) is considered the primary dietary toxic element. Previous studies have demonstrated significant differences in heavy metal accumulation among crop species. However, this information in karst areas with low heavy metal activity is missing. In this study, the uptake and accumulation characteristics of cadmium in soil-crop samples of group 504 in the core karst region of East Asia were analyzed. Cadmium low-accumulating maize and rice were screened using cluster and Pareto analytic methods. In addition, a new method, the species-sensitive distribution model (SSD), was proposed, which could be used to estimate the environmental threshold for cadmium in regional cropland. The results showed that both maize and rice soils in the research area were contaminated with varying degrees of cadmium. The total concentrations of cadmium ω(T-Cd) in maize and rice fields are 0.18-1.32 and 0.20-4.42 mg kg-1, respectively. The ω(T-Cd) of heavy metals in maize kernels and rice grains is 0.002-0.429 and 0.003-0.393 mg kg-1, respectively. The bioaccumulation factor (BCF) of cadmium in maize ranged from 0.0079 to 0.9701, with a coefficient of variation of 1.71; the BCF of cadmium in rice ranged from 0.0074 to 0.1345, with a coefficient of variation of 0.99. According to cluster and Pareto analyses, the maize crop varieties with low cadmium accumulation suitable for local cultivation were screened as JHY809, JDY808, AD778, SN3H and SY13, and the rice varieties were DMY6188, GY725, NY6368, SY451 and DX4103. In addition, the environmental cadmium threshold ranges of 0.30-10.05 mg kg-1 and 0.89-24.39 mg kg-1 for maize and rice soils, respectively, were deduced in this study. This threshold will ensure that 5-95% of maize and rice will not be contaminated with cadmium in the soil.

The spatial-temporal distribution and etiological characteristics of hand-foot-and-mouth disease before and after EV­A71 vaccination in Kunming, China, 2017-2020.

After vaccination with enterovirus 71 (EV-A71), the prevalence of hand-foot-and-mouth disease (HFMD) remained high, and the spatial-temporal distribution of enteroviruses changed. Therefore, it is essential to define the temporal features, spatial distributions, and epidemiological and etiological characteristics of HFMD in Kunming. Between 2017 and 2020, a total of 36,540 children were diagnosed with HFMD in Kunming, including 32,754 children with enterovirus-positive clinical samples. Demographic, geographical, epidemiological and etiological data of the cases were acquired and analyzed. Other enteroviruses replaced EV-A71, and the incidence of EV-A71 decreased dramatically, whereas coxsackievirus A6 (CV-A6) and coxsackievirus A16 (CV-A16) had substantial outbreaks in 2018 and 2019, respectively. The major and minor peaks all extended for 2-4 months compared to before vaccination with the EV-A71 vaccine. From 2019 to 2020, CV-A6, as the predominant serotype, showed only a single peak. Although a high incidence of HFMD was observed in Guandu, Chenggong and Xishan, the annual incidence of different enterovirus serotypes was different in different regions. In 2017, other enteroviruses were most prevalent in Shilin. In 2018, CV-A16 and CV-A6 were most prevalent in Luquan and Shilin, respectively. In 2019, CV-A16 was most prevalent in Jinning. In 2020, CV-A6 and coxsackievirus A10 (CV-A10) were most prevalent in Luquan and Shilin, respectively. Meanwhile, the epidemic cycle of CV-A6 and CV-A16 was only 1 year, and CV-A10 and other enteroviruses were potential risk pathogens. The spatial and temporal distribution of HFMD varies at different scales, and the incidence of HFMD associated with different pathogens has obvious regional differences and seasonal trends. Therefore, research on multivalent combined vaccines is urgently needed, and proper preventive and protective measures could effectively control the incidence of HFMD-like diseases.

Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments.

Sometimes, people can be exposed to moderate or high doses of radiation accidentally or through the environment. Radiation can cause great harm to several systems within organisms, especially the hematopoietic system. Several types of drugs protect the hematopoietic system against radiation damage in different ways. They can be classified as "synthetic drugs" and "natural compounds." Their cellular mechanisms to protect organisms from radiation damage include free radical-scavenging, anti-oxidation, reducing genotoxicity and apoptosis, and alleviating suppression of the bone marrow. These topics have been reviewed to provide new ideas for the development and research of drugs alleviating radiation-induced damage to the hematopoietic system.

[Health Risk Assessment and Environmental Benchmark of Heavy Metals in Cultivated Land in Mountainous Area of Northwest Guizhou Province].

An extensive investigation of heavy metal (Cd, Hg, As, Pb, and Cr) levels in 137 pairs of soil-maize/rice samples was conducted in cultivated land from a typical karst mountain area in the Northwest of Guizhou Province. A health risk assessment model was used to assess the health risks of those areas, and the environmental benchmarks of heavy metals in soils were evaluated using the species sensitivity distribution (SSD) model. The results showed that the soils of maize and rice were polluted by heavy metals. Cd was the primary pollutant, with an exceeding rate ranging from 87% to 445%. The contaminated level of maize fields was higher than those of rice fields. In contrast, only 3.51% and 13.4% of Cd content in maize kernels and rice grains exceeded the national threshold, and the Cd heavy metal accumulation ability of rice was higher than that of maize. The carcinogenic and non-carcinogenic risks of heavy metals for adults and children in the study area were at a low level. The carcinogenic risk of rice consumption was slightly higher than that of maize, and the health risk to children was higher than that to adults. The results derived from the SSD method showed that the 95% and 5% hazardous concentrations (HC5 and HC95) of maize fields were 0.67 for Cd, 771.99 for As, 40.85 for Pb and 609.88 for Cr mg·kg-1, and HC95were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of rice fields were 2.42 for Cd, 8.88 for As, 41.41 for Pb and 27.84 for Cr mg·kg-1, and the HC95 values were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of Cd, As, and Cr in maize fields and Cd in rice fields were significantly higher than the soil risk screening values in the current standard, and the HC95 values of the two fields were higher than the soil risk intervened values. The results indicated that the current standard would be too strict to evaluate the actual pollution level of soil heavy metals in this area.

Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells.

This study tested the ability of a fermented soy product to induce tumor cell toxicity and to assess if this was due to fermentation of soy, and to the genistein content. Four cancer cell lines were cultured without additive, with fermented soy (Q-CAN® PLUS), nonfermented soy, or genistein, and cell viability was examined at 24 h, 48 h, and 72 h. The sensitivity of the cell lines to apoptosis by Q-CAN PLUS was tested with the Annexin V assay. All cell lines demonstrated a dose and time response reduction in tumor cell viability with exposure to Q-CAN PLUS (IC50 at 24 h 3.8 mg/mL to 9 mg/mL). Unfermented soy did not show reduction in viability of any cell line within the same concentration range. The IC50 of genistein for each of the cell lines was significantly greater than for Q-CAN PLUS. All four tumor cell lines demonstrated apoptosis in response to Q-CAN PLUS. Q-CAN PLUS reduces viability and increases apoptosis of cancer cells in a concentration- and fermentation-dependent manner. Taking into consideration the IC50 of genistein and the concentration of genistein in Q-CAN PLUS, the genistein content of Q-CAN PLUS is not responsible for the majority reduction in tumor cell viability. This suggests that fermentation of soy results in the production of metabolites that reduce cancer cell viability and induce cellular apoptosis, and play a major role in addition to any effects produced by their genistein content.

Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity.

Infiltration of regulatory T cells (Tregs) in the tumor microenvironment suppresses anti-tumor immune response, and promotes tumor progression. Tumor necrosis factor receptor-2 (TNFR2), which is highly expressed on Tregs, activates Tregs through nuclear factor kappa B (NF-κB) pathway. Moreover, TNFR2+ Tregs have been shown to be most suppressive among all Tregs populations in tumor. Due to the unique expression pattern and function of TNFR2 on Tregs, a TNFR2 blocking antibody is expected to compromise Tregs function, relieve Tregs-mediated immunosuppression, and hence to enhance anti-tumor immune response. AN3025 is an antagonistic anti-human TNFR2 (hTNFR2) antibody that is currently under preclinical development. This study investigates the immunomodulatory and anti-tumor activity of AN3025. AN3025 was generated through rabbit immunization with extracellular domain of human TNFR2 and subsequent humanization by complementarity-determining regions (CDRs) grafting. AN3025 binds to the extracellular domain of both human and cynomolgus with sub-nanomolar affinity and specificity, but not mouse or rat TNFR2. AN3025 inhibited tumor necrosis factor alpha (TNFα) induced cell death of hTNFR2-overexpressing Jurkat cells by competing with TNFα for binding to hTNFR2. In the Tregs/T effector co-culture assay, AN3025 increased T effector proliferation and enhanced interferon gamma (IFNγ) production. As a monotherapy, AN3025 significantly inhibited MC38 tumor growth in TNFR2 humanized mouse model. Subsequent flow cytometry (FACS) and immunohistochemistry (IHC) analysis revealed that administration of AN3025 led to decreased Tregs population, increased CD4+ and CD8+ T cell numbers in the tumor. The anti-tumor activity of AN3025 was dependent on the existence of CD4+ and CD8+ T cells, as depletion of CD4+ and CD8+ T cells abolished the anti-tumor activity of AN3025. In addition, AN3025 in combination with anti-PD-1 antibody demonstrated stronger in-vivo anti-tumor activity. The potent anti-tumor efficacy of AN3025, either as a monotherapy or in combination with anti-PD-1 antibody, supports its further clinical development for the treatment of various human tumors.