OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G₁ phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION TPA induces NB4 cell cycle arrest in G₁ phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Humans ; Leukemia, Promyelocytic, Acute ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Cell Division ; Apoptosis ; RNA, Messenger ; Cell Proliferation

Purpose: The consequences of severe traumatic injury extend beyond hospital admission and have the potential for long-term functional, psychological, and economic sequalae. This study investigated patient outcomes 6 months following major trauma. Methods: Using the National Trauma Registry, database of patients who were admitted between 2016-18 in a tertiary trauma hospital for major trauma [Injury Severity Score (ISS) ≥ 16] a review was performed on 6-month outcomes [including functional outcomes, self-reported state of health and outcome scores (EuroQol-5 Dimension score and Glasgow Outcome Scale Extended)].Result: There were 637 patients who were treated for major trauma (ISS ≥ 16); the median age was 64 years (range 16-100) and 435 (68.3%) patients were male. The most common injury mechanisms included falling from height (56.5%) and motor vehicle accident (27.0%). The median ISS was 24 (range 16-75). After 6 months, 87.6% of responders were living at home, 25.0% were back to work, and 55.1% were ambulating independently. The median self-rated state of health was 73 at baseline and 64 at 6 months. Age and length of stay were independent predictors of return to ambulation using multivariate analysis. Age, Abbreviated Injury Scale external, Glasgow Coma Scale on Emergency Department arrival, heart rate, and need for transfusion were independent predictors of failure to return to work at 6 months using multivariate analysis. Charlson Comorbidity Index, Glasgow Coma Scale on arrival, temperature, pain and need for inpatient rehabilitation were independent predictors of mortality at 6 months. Conclusion Recovery from major trauma is multi-faceted and requires a team-based approach well beyond discharge.

Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves’ disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs’ formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.
Diphosphonates ; Hyperthyroidism

Infant, Newborn ; Humans ; Macrophage Activation Syndrome/diagnosis*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*