Objective To explore the causal relationships between 13 micronutrients (copper, selenium, zinc, calcium, folate, iron, magnesium, vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, and vitamin E) and risk of tuberculosis (TB) through a two-sample Mendelian randomization (MR) study. Methods The Genome-Wide Association Study (GWAS) data about micronutrients and TB were obtained from the IEU Open GWAS and FinnGen Biobank, and Bayesian Weighted Mendelian Randomization (BWMR) and Inverse Variance Weighted (IVW) methods were employed to explore the causal relationship between micronutrients and risk of TB. The robustness and reliability of the results were assessed through horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity analyses. Results The BWMR results indicated that iron (OR = 0.40, 95% CI : 0.20- 0.79, P = 0.008) and vitamin C (OR = 0.42, 95% CI : 0.20 - 0.87, P = 0.019) were protective factors against TB infection, while no causal relationships were found between other micronutrients with TB infection. The IVW method produced consistent results with BWMR. The results for other micronutrients were robust and reliable (P > 0.05), except for calcium-related Instrumental Variables (IVs), which exhibited heterogeneity (P < 0.05). Conclusion Iron and vitamin C may play a protective role in reducing the risk of TB, whereas the remaining micronutrients show no significant causal relationship with TB.

Objective To investigate the effects of ubiquitin-like modifier activating enzyme 1(UBA1) on the proliferation and apoptosis of acute myeloid leukemia(AML) cells(HL60 and THP-1 cells) and its mechanism, so as to evaluate the possibility of using UBA1 as a molecular marker and target for diagnosis and treatment of AML. Methods The expression of UBA1 in HL60 and THP-1 cells was inhibited via shRNA interference, and stable transfection cell lines were screened. The inhibition effect was detected by qPCR and Western blot. The effect of inhibiting UBA1 on proliferation of AML cells was measured by CCK-8 assay. Flow cytometry was used to detect the effect of inhibiting UBA1 on apoptosis of AML cells. The effects on the expression of apoptosis proteins(Bax, Bc12), cell cycle regulation related proteins(CDK4, CDK6 and CyclinD1) and MAPK signaling pathway related proteins(P-ERK, P-JNK, P-P38MAPK, T-ERK, T-P38) in AML cells were determined by Western blot. Results Following UBA1 knockdown, both HL60 and THP-1 cells exhibited a significant reduction in UBA1 mRNA transcription and protein expression levels(t = 2. 065-43. 591, each P < 0. 05). Cell proliferation capacity was significantly suppressed(t = 12. 274-17. 252, each P < 0. 05), while the apoptosis rate increased significantly(t = 12. 690-18. 855, P <0. 05). The pro-apoptotic protein Bax was significantly upregulated(t = 17. 094-20. 781, P < 0. 01), whereas the anti-apoptotic protein Bcl-2 was downregulated(t = 42. 494-53. 050, P < 0. 01). The expression levels of cell cycle regulatory proteins CDK4, CDK6, and Cyclin D1 all significantly decreased(t = 12. 193-51. 666, each P < 0. 05). The expression levels of P-ERK and P-P38MAPK in MAPK signaling pathway increased significantly(t = 3. 759-10. 822, each P < 0. 05),but the expression levels of P-JNK, T-ERK and T-P38 had no statistically significant difference(t = 0. 133-1. 794, each P >0. 05). Conclusion Interference with the expression of UBA1 can inhibit the proliferation of HL60 and THP-1 cells and promote their apoptosis, of which the mechanism may be related to the increased expression of P-ERK and P-P38MAPK proteins in MAPK signaling pathway.

OBJECTIVE: To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation. METHODS: A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared. RESULTS: A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (F_time = 105.975, P < 0.001), intervention effects (F_intervention = 7.378, P = 0.008), and interaction effects (F_interaction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO₂) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO₂) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05]. CONCLUSIONS Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans ; Transcutaneous Electric Nerve Stimulation ; Respiration, Artificial/adverse effects* ; Diaphragm/physiopathology* ; Phrenic Nerve ; Intensive Care Units ; Male ; Female ; Middle Aged

Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage. It plays a central role in the pathological progression of diverse diseases, including psychiatric disorders, cancer, and immunological conditions, rendering it an essential target for therapeutic intervention. Periodontitis, a prevalent oral inflammatory disease, is a leading cause of tooth loss and poses significant health challenges globally. Traditionally, inflammatory diseases such as periodontitis have been treated with systemic administration of synthetic chemicals. However, recent years have witnessed challenges, including drug resistance and microbial dysbiosis associated with these treatments. In contrast, natural products derived from Chinese medicine offer numerous benefits, such as high safety profiles, minimal side effects, innovative pharmacological mechanisms, ease of extraction, and multiple targets, rendering them viable alternatives to conventional antibiotics for treating inflammatory conditions. Numerous effective anti-inflammatory natural products have been identified in traditional Chinese medicine (TCM), including alkaloids, flavonoids, terpenoids, lignans, and other natural products that exhibit inhibitory effects on inflammation and are potential therapeutic agents. Several studies have confirmed the substantial anti-inflammatory and immunomodulatory properties of these compounds. This comprehensive review examines the literature on the anti-inflammatory effects of TCM-derived natural products from databases such as PubMed, Web of Science, and CNKI, focusing on terms like "inflammation", "periodontitis", "pharmacology", and "traditional Chinese medicine". The analysis systematically summarizes the molecular pharmacology, chemical composition, and biological activities of these compounds in inflammatory responses, alongside their mechanisms of action. This research seeks to deepen understanding of the mechanisms and biological activities of herbal extracts in managing inflammatory diseases, potentially leading to the development of promising new anti-inflammatory drug candidates. Future applications could extend to the treatment of various inflammatory conditions, including periodontitis.
Humans ; Periodontitis/immunology* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional ; Animals ; Anti-Inflammatory Agents/chemistry*

Apolipoprotein D(APOD)is a protein that is widely present in animal tissues and is in-volved in the reproductive regulation of the body.In order to investigate the expression regularity of APOD in bactrian camel epididymis and its regulation effect on sperm maturation,this study took the epididymis of bactrian camel during estrus and anestrus as materials,and first cloned the complete sequence of APOD coding sequence(CDS)region.The physicochemical properties of AP-OD were analyzed by ProParam,SOPMA,SWISS-MODEL and MEGA7.0 software.Meanwhile,the expression and distribution of APOD in epididymis were detected by qRT-PCR,Western blot and IHC.The cloning results showed that:the length of the CDS region of APOD gene was 624 bp,encoding 207 amino acids.The APOD sequence of Bactrian camel was highly conserved with the nucleotide and amino acid sequence of alpaca,and the homology of APOD sequence with elk was the lowest.The results of qRT-PCR showed that the mRNA levels of APOD in the head,body and tail of epididymis in estrus were significantly higher than those in estrus(P＜0.01).Western blot results showed that the APOD protein expression and mRNA expression trend was similar in the head and body of the epididymis during anestrus,but the APOD expression level in the tail of the epididymis during anestrus was opposite to the mRNA expression level(P＜0.05).The results of H&E and IHC showed that there were significant differences in epididymal tissue between estrus and anestrus.In addition,APOD showed positive reactions in epididymal epithelial cells,smooth muscle cells,sperm and connective tissue to varying degrees,suggesting that APOD may be in-volved in the maturation of sperm during estrus and anestrus,providing evidence for further explo-ring the regulatory mechanism of APOD's involvement in seasonal estrus.

Objective:To analyze the levels of thrombin generation and activated protein C resistance (APC-R) in lupus anticoagulant (LA)-positive patients, and to assess their effectiveness in predicting thrombotic risk in these patients.Methods:Retrospective case-control study. A total of 185 patients with positve LA [91 males, 94 females; age (47.59±19.14) years] in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from November 1st, 2024 to March 31st, 2025 were included. Patients were stratified into thrombotic ( n=91) and non-thrombotic groups ( n=94) based on clinical diagnosis and imaging evidence of thrombosis. The basic characteristics and routine laboratory coagulation levels of LA-positive patients were analyzed. Post-test plasma samples were collected from 43 cases with positive or strongly positive LA, categorized into thrombotic ( n=23) and non-thrombotic ( n=20) groups. Additionally, plasma was collected from 80 healthy controls [40 males and 40 females, age (38.37±15.74) years]. Using simple random sampling method, plasma samples from 10 selected males and 10 selected females were mixed to make 1 group of healthy control, thus accordingly resulted in a total of 4 healthy control groups. Thrombin generation assays (TGA) were then employed to measure prothrombin generation and activated protein C resistance (APC-R) levels in the healthy control, non-thrombotic, and thrombotic groups. One-way analysis of variance was utilized to compare thrombin generation and APC-R levels across these groups. Results:Among the routine laboratory coagulation indexes, the median levels of activated partial thromboplastin time (APTT), fibrin degradation product (FDP) and protein C (PC) in thrombotic group were 30.9 (28.8, 35.5) s, 2.5 (1.3, 2.8) mg/L, and 107.0 (93.0, 127.0)%, respectively, which were significantly higher compared with the non-thrombosis group (all P<0.05). However, between the thrombotic and non-thrombotic group, no statistically significant differences were observed for the levels of prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), or D-dimer (D-D) ( P>0.05). The TGA results showed that the total thrombin generation, the maximal thrombin generation and APC-R levels of patients in the thrombotic group were (1 118.72±387.34) nmol/L·min, (106.01±59.00) nmol/L and (0.33±0.22), respectively, which were significantly higher compared with those in the non-thrombotic group (all P<0.05). Conclusion:Significantly increased thrombin generation and enhanced APC-R were present in the LA-positive patients with thrombosis, indicating the important values of thrombin generation and APC-R in assessing thrombosis risk among this population.

Objective:To compare the changes in fracture displacement under different vertical loadings between the 2 different internal fixation modalities for vertically unstable femoral neck fractures of Pauwels type Ⅲ by a mechanical study and a finite element analysis.Methods:Twelve biomimic bones were transversely dissected from 10 cm below the lesser trochanter of the femur to create femoral neck fracture models with a Pauwels angle of 70° using a swing saw. The models were equally divided into 2 groups ( n=6): group A was fixed with 3 cannulated screws after fracture reduction (scheme A), and group B with 3 cannulated screws plus a self-designed anteromedial support plate after fracture reduction (scheme B). Continuous vertical force was applied using a mechanical testing machine. Changes in displacement were recorded and load-displacement curves were plotted. One volunteer (female, 28 years old, 168 cm in height and 65 kg in weight) was selected for finite element analysis of her CT images of both lower limbs to examine the maximum displacement and the maximum Mises stress in scheme A and scheme B respectively. Results:In groups A and B respectively: All the 6 biomimic mimetic bones had similar load and displacement curves, and similar fracture displacements (Dx) at different loading points (N X); the curves of 6 biomimic bones were highly fitted with S-shaped curve equation (the r-square value was close to 1). At the initial loading stage (0 N0.05). When the load was 100 N

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

Objective:To investigate the clinical effects of the anterolateral thigh perforator flaps transplantation in repairing the wounds after radical resection of skin malignant tumors in the head, face, and neck.Methods:This study was a retrospective observational study. From May 2020 to December 2023, 27 patients with skin malignant tumors in the head, face, and neck were admitted to the Department of Burns and Plastic Surgery of the First People's Hospital of Kashi Prefecture, including 19 males and 8 females, aged 53 to 89 years. There were 21 cases with squamous cell carcinoma and 6 cases with basal cell carcinoma. The wound area after radical resection of tumors was 9.0 cm×7.0 cm to 27.0 cm×21.5 cm. The wounds were repaired with the lobulated, combined, or various forms of combination of the anterolateral thigh perforator flaps, and the harvesting flap area in single donor site was 10.0 cm×8.0 cm to 27.0 cm×11.0 cm. The wounds in the flap donor sites were closed by suturing in 26 patients, while the wound in the flap donor site in 1 patient was repaired with medium-thickness skin graft in the lower leg. The survival of the flap, and the occurrence of vascular crisis and infection were observed after surgery. During follow-up after surgery, the tumor recurrence, shape and texture of the flaps, and the function and scar formation of the limbs where the donor site was located were observed.Results:Only one patient developed venous crisis of the flap 27 hours after surgery, and the flap survived after vascular exploration and reanastomosis of the vein; the flaps in the other patients survived after surgery. One patient had an infected effusion under the flap after surgery, which healed after dressing change. After 6-36 months of postoperative follow-up, no tumor recurrence was observed; the flap had good appearance, texture, and elasticity; the limb where the donor site was located functioned normally, with only linear scars left.Conclusions:For complex wounds after radical resection of skin malignant tumors in the head, face, and neck, different forms of anterolateral thigh perforator flaps can be used to repair the wounds according to the condition of the wounds, and the wounds in the recipient sites heal well after surgery, with minimal damage to the donor site.

Objective To investigate the expression of ferritinophagy-related gene ELAV-like RNA binding protein 1(ELAVL1)in multiple myeloma(MM)and elucidate its diagnostic and prognostic value for MM.Methods First,we analyzed ELAVL1 expression level in healthy controls and MM patients using data from the GEO and TCGA databases.Subsequently,bone marrow specimens were collected from 28 newly diagnosed MM patients and 20 healthy controls,and qRT-PCR was employed to validate ELAVL1 expression.The diagnostic and prognostic potential of ELAVL1 was assessed using ROC curve analysis and Kaplan-Meier survival curves.Additionally,univariate and multivariate COX regression analyses were performed to identify independent risk factors for MM prognosis.Finally,KEGG and GO enrichment analyses were performed using the DAVID online platform.Results The level of ELAVL1 expression was significantly higher in newly diagnosed MM patients and refractory/relapsed MM patients than in the healthy controls(P＜0.001).Moreover,ELAVL1 expression was positively correlated with the International Staging System(ISS)stage of MM(P＜0.01).Furthermore,qRT-PCR validation confirmed that ELAVL1 expression was elevated in the 28 newly diagnosed MM patients compared to the 20 healthy controls(P＜0.001).ROC curve analysis demonstrated that ELAVL1 could effectively differentiate between newly diagnosed MM patients,healthy controls,and MGUS patients(P＜0.001 and P=0.000 2,respectively).Survival analysis revealed that high ELAVL1 expression was associated with shorter progression-free survival(P=0.0141)and overall survival(P=0.008 0).Univariate and multivariate COX regression analyses identified high ELAVL1 expression as an independent risk factor for poor MM prognosis(P=0.005 0).KEGG analysis suggested that ELAVL1 might be involved in the Hippo and MAPK signaling pathways.Conclusion High ELAVL1 expression in MM may serve as a biomarker for diagnosis and poor prognosis.ELAVL1 may promote MM initiation and progression via the Hippo and MAPK signaling pathways.