Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Objective:To learn about the epidemiological and clinical characteristics of human brucellosis in Shaanxi Province, and to provide reference for brucellosis prevention and control.Methods:Through the China Disease Control and Prevention Information System and the Shaanxi Provincial Brucellosis Prevention and Control Work System, report data and case investigation data on human brucellosis cases in Shaanxi Province from 2020 to 2022 were collected, respectively, and the epidemiological characteristics, exposure history and clinical manifestations of the cases were analyzed descriptively.Results:A total of 4 240 human cases of brucellosis were reported in Shaanxi Province from 2020 to 2022, with no death. The average annual incidence was 3.60/100 000, with an average growth rate of 22.33%. Cases of brucellosis were reported from January to December throughout the year, mainly from April to August, accounting for 63.40% (2 688/4 240). Cases of brucellosis were reported in 12 prefectures (including Yangling District and prefecture-level administrative divisions directly administered by the province) and 90 counties (districts and cities), accounting for 79.65% (90/113) of the total number of counties (districts and cities). The male to female ratio of the cases was 2.92 ∶ 1.00 (3 159 ∶ 1 081). The onset age was mainly from 30 to 74 years old, accounting for 89.81% (3 808/4 240). Farmer was the main occupation, accounting for 87.12% (3 694/4 240). A total of 4 223 cases were investigated in Shaanxi Province from 2020 to 2022, with the acute phase being the main stage of disease progression, accounting for 94.67% (3 998/4 223); hospitalized cases accounted for 59.79% (2 525/4 223); the main risk occupations of brucellosis were rearing and grazing, accounting for 78.43% (3 312/4 223). The main exposure routes were direct contact through skin and mucous membranes and respiratory infection, accounting for 95.07% (4 015/4 223). There were 4 015 cases with a history of contact with livestock and their products, with sheep being the main type of contact (accounting for 96.91%, 3 891/4 015), and the possible infection sites were mainly at home (58.53%, 2 350/4 015). The main clinical symptoms were fever, muscle and joint pain, fatigue and excessive sweating, accounting for 75.49% (3 188/4 223), 58.23% (2 463/4 223), 68.17% (2 879/4 223) and 63.65% (2 688/4 223), respectively. A total of 139 Brucella strains were isolated and cultured, with sheep type 3 being the main bacterial type, accounting for 75.54% (105/139). Conclusions:The epidemic of brucellosis in Shaanxi Province is showing a clear upward trend, and the scope of the epidemic is becoming wider and wider. The incidence of brucellosis is mainly in free-range households, and the course of the disease is mostly in the acute phase. Brucellosis is mainly caused through direct contact with the skin and mucous membranes and respiratory infections. The clinical manifestations are diverse but non-specific. It is necessary to effectively improve the personal protection awareness and level of high-risk groups to reduce the occurrence of brucellosis.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.

Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.

Objective:To investigate the effect of berberine on immune regulation and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway in lung cancer rats.Methods:The lung cancer rat model was established by perfusing a carcinogenic lipiodol solution. The 36 male Wistar rats were randomly divided into the model group ( n = 12), the berberine group ( n = 12), and the normal group ( n = 12). The rats in the berberine group were ig berberine 15 mg/kg, once daily. The rats in the model group and the normal group were ig the same dose of normal saline, once daily. The intervention was conducted continuously for 16 weeks for each group. The spleen index and lung index, tumor inhibition rate, T lymphocyte subgroup level, PI3K, and Akt protein expression of rats in each group were compared. Results:The spleen index of the model group and berberine group was lower than that of the normal group, while the lung index was higher than that of the normal group (all P < 0.05). The spleen index of the berberine group was higher than that of the model group, while the lung index was lower than that of the model group (all P < 0.05). The tumor weight of the berberine group was lower than that of the model group ( P < 0.05). The tumor inhibition rate of the berberine group was 43.12%. The CD3 +, CD4 +, and CD4 +/CD8 + levels of the model group and berberine group were lower than those of the normal group, CD8 + level was higher than that of the normal group (all P < 0.05), and the CD3 +, CD4 + and CD4 +/CD8 + levels of the berberine group higher than those of the model group, while CD8 + level was opposite (all P < 0.05). The gray values of PI3K and Akt protein of the model group and berberine group were higher than those of the normal group (all P < 0.05), and this value of the berberine group was lower than that of the model group (all P < 0.05). Conclusions:Berberine can effectively inhibit tumor growth in lung cancer rats, promote spleen development and differentiation, regulate immune function, and downregulate the expression of PI3K/Akt signaling pathway.

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

Human salivary histatin 1 (Hst1) exhibits a series of cell-activating properties, such as promoting cell spreading, migration, and metabolic activity. We recently have shown that fluorescently labeled Hst1 (F-Hst1) targets and activates mitochondria, presenting an important molecular mechanism. However, its regulating signaling pathways remain to be elucidated. We investigated the influence of specific inhibitors of G protein-coupled receptors (GPCR), endocytosis pathways, extracellular signal-regulated kinases 1/2 (ERK1/2) signaling, p38 signaling, mitochondrial respiration and Na+/K+-ATPase activity on the uptake, mitochondria-targeting and -activating properties of F-Hst1. We performed a siRNA knockdown (KD) to assess the effect of Sigma-2 receptor (S2R) /Transmembrane Protein 97 (TMEM97)-a recently identified target protein of Hst1. We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1. Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1. The inhibitors of GPCR, ERK1/2, phagocytosis, and clathrin-mediated endocytosis (CME) as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake, which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity. Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1. We further showed the intracellular trafficking and targeting process of F-Hst1, in which early endosome plays an important role. Overall, phagocytosis, CME, GPCR, ERK signaling, and S2R/TMEM97 are involved in the internalization of Hst1, while only CME and S2R/TMEM97 are critical for its subcellular targeting. The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.
Endocytosis/physiology* ; Histatins/pharmacology* ; Humans ; Membrane Proteins ; Mitochondria/metabolism* ; RNA, Small Interfering/pharmacology* ; Receptors, G-Protein-Coupled/metabolism* ; Receptors, sigma

Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula (BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease (PD) cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate (ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mito-chondrial morphology,activity,and mitochondrial membrane potential (ΔΨm).Western blot was con-ducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynamin-related protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPP+-induced mitochondrial damage,increased mitochon-drial activity and AΨm.BYQZF increased the survival of MPP+-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the ΔΨm and ATP levels.These findings suggested that BYQZF protected against MPP+-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1 (closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamic-related protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPP+-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.

Objective:To compare the effect of systematic nursing in operating room and routine nursing in reducing intraoperative stress injury in patients with spinal fracture and spinal cord injury.Methods:A retrospective case-control study was conducted to analyze the clinical data of 285 patients with cervical or thoracolumbar fracture associated with spinal cord injury admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2018 to December 2019, including 168 males and 127 females, with the age of 38-59 years [(47.8±8.5)years]. All patients underwent posterior decompression and fusion with internal fixation. Of all, 138 patients received systematic nursing in operating room including systematic evaluation and management before, during and after operation (observation group), and 147 patients received routine nursing including only intraoperative preventive care of pressure ulcer (control group). The incidence of pressure injury on the day after operation, degree of injury and location of injury at postoperative 3 days, and area of injury on the day after operation and at postoperative 3 days were compared between the two groups. The degree of injury was evaluated using the new stress injury staging assessment published by the American National Pressure Ulcer Advisory Panel (NPUAP).Results:The incidence of pressure injury in observation group [5.1% (7/138)] was lower than that in control group [12.2% (18/147)] on the day after operation ( P<0.05). The incidence of stage I, stage II, and stage III pressure injury in observation group [2.9% (4/138), 2.2% (3/138), 0.0%] was also lower than that in control group [8.2% (12/147), 3.4% (5/147), 0.6% (1/147)] at postoperative 3 days ( P<0.05). There was no significant difference in the incidence of pressure injury in the knee, chest, face and anterior superior iliac spine between the two groups ( P>0.05). The total proportion of pressure injury in the face and anterior superior iliac spine was 71% (5/7) in observation group, showing no significant difference from that in control group [83% (15/18)] ( P>0.05). The area of injury was (3.2±1.2)cm 2 and (3.2±1.1)cm 2 in observation group on the day after operation and at postoperative 3 days, lower than that in in control group [(5.1±1.5)cm 2 and (5.1±1.4)cm 2] ( P<0.01). Conclusion:Compared with the routine nursing, systematic nursing in operating room can significantly reduce the incidence, degree and area of intraoperative pressure injury in patients with spinal fracture accompanied by spinal cord injury, and deserves clinical promotion.