Polymyxin serves as the"last line of defense"for treating infection with multidrug-resistant Gram-ne-gative bacteria.However,the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy.This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin,comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects:natural compounds,synthetic small molecules,and drug repurposing.Furthermore,this paper explores the innovative strategies of gene intervention,new targets,and nanotechnology-based formulations in the develop-ment of sensitizer,aiming to provide systematic theoretical support and research ideas against polymyxin resistance.

This study investigated the functions and regulatory mechanism of Portulacae Herba and its chemical components on the Toll-like receptor 4(TLR4)/myeloid differentiation primary response 88(MyD88)/nuclear factor kappa B(NF-κB) inflammatory signaling pathway in the colon tissue of mice with dextran sodium sulfate(DSS)-induced ulcerative colitis(UC). A total of 35 mice were randomly divided into groups, including a blank group, a model group, a mesalazine group(0. 5 g·kg~(-1)), and low, medium,and high dose alkaloids from Portulacae Herba groups(9, 18, 36 mg·kg~(-1)), and a combination treatment group, with 5 mice in each group. The blank group was given purified water, while the other groups were continuously given a 3% DSS solution for 7 days to induce the UC model. From day 8 onwards, the treatment group received oral gavage according to the prescribed doses for 14 days. The overall condition, body weight, stool characteristics, and presence of blood in the stool were recorded daily. After the experiment, the disease activity index(DAI) was assessed for each group, and colon length was measured. Histopathological changes in colon tissue were examined using hematoxylin-eosin(HE) staining. The levels of pro-inflammatory cytokines, tumor necrosis factor-α(TNF-α),and interleukin-1β( IL-1β) in serum were measured by enzyme-linked immunosorbent assay( ELISA). The protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were measured using Western blot and quantitative real-time PCR(qPCR).Compared to the blank group, the model group showed a significant decrease in body weight, a notable increase in DAI scores, a significant shortening of colon length, and evident histopathological damage. The levels of inflammatory cytokines TNF-α and IL-1β in the serum were significantly elevated, and the protein and m RNA expression of TLR4, MyD88, and NF-κB in colon tissue were significantly up-regulated. In contrast, the alkaloids from Portulacae Herba treatment groups significantly improved symptoms and reduced body weight loss in mice, decreased DAI scores, alleviated colon shortening, lowered serum levels of TNF-α and IL-1β,significantly down-regulated the expression levels of TLR4, MyD88, and NF-κB proteins and genes in colon tissue, as well as reduced histopathological damage. Therefore, the study suggests that alkaloids from Portulacae Herba can alleviate intestinal inflammation damage in DSS-induced UC mice, with its mechanism involving the TLR4/MyD88/NF-κB signaling pathway.
Animals ; Colitis, Ulcerative/immunology* ; Toll-Like Receptor 4/immunology* ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Male ; Alkaloids/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Female ; Colon/metabolism* ; Disease Models, Animal

Polymyxin serves as the"last line of defense"for treating infection with multidrug-resistant Gram-ne-gative bacteria.However,the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy.This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin,comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects:natural compounds,synthetic small molecules,and drug repurposing.Furthermore,this paper explores the innovative strategies of gene intervention,new targets,and nanotechnology-based formulations in the develop-ment of sensitizer,aiming to provide systematic theoretical support and research ideas against polymyxin resistance.

Objective To analyze the difference of diseases between the coal mine workers and the general population inpatients by the disease spectrum in Datong City. Methods A total of 282 639 hospitalized patients in Datong City in 2023 were included as the study subjects. Participants were divided into a general population group and a coal mine workers group based on health insurance types, with 247 897 and 34 742 cases, respectively. The disease spectrum of participants in both groups was coded and analyzed according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The standardized constituent ratios of disease categories were calculated and compared between the two groups. Results Patients aged 60-<70 years had the largest standardized proportion in both cohorts (29.02% in the general population group and 33.08% in coal mine workers group). Circulatory system diseases had the highest standardized proportion in both groups. Within the top six disease categories ranked by standardized composition ratio in the coal mine workers, three demonstrated a higher burden, including neoplasms (C00-D48), symptoms, signs and abnormal clinical/laboratory findings not elsewhere classified (R00-R99), and factors influencing health status/contact with health services (Z00-Z99), compared with the general population (11.82% vs 10.44%, 12.99% vs 8.03%, and 6.17% vs 2.04%, respectively). In both groups, male workers had higher standardized constituent ratios of circulatory, respiratory, and digestive system diseases than females (coal mine workers group, 19.53% vs 14.31%, 13.56% vs 9.10%, 10.61% vs 8.43%; general population group, 26.15% vs 22.42%, 15.45% vs 11.87%, 11.52% vs 10.41%). Conversely, the ratios for conditions classified under symptoms, signs and abnormal clinical/laboratory findings not elsewhere classified (R00-R99). and factors influencing health status/contact with health services (Z00-Z99) were higher in females than males (coal mine workers group, 13.31% vs 12.68%, 7.26% vs 5.13%; general population group, 8.91% vs 7.18%, 2.35% vs 1.74%). Mental and behavioral disorders (F00-F99) were most prevalent in the 22-<50-year age group in the general population (9.92%) and in the 50-<60-year age group in coal mine workers (8.58%). The standardized proportion of respiratory system diseases ranked first in≥80-year age workers in general population group and coal mine workers group (29.54% and 26.46%, respectively). Regarding specific malignancies, unspecified malignant neoplasm of the bronchus or lung was the most common cancer among males in both groups (3.44% and 3.62%). Among females, the standardized proportion of unspecified malignant neoplasm of breast was higher in coal mine workers group than in the general population group (2.60% vs 2.09%). Conclusion Neoplasms, abnormal symptoms, and mental health disorders should be prioritized in disease prevention strategies for coal mine workers. Greater attention should be paid to mental health screening in younger populations, and medical resource allocation should be optimized according to sex-specific high-incidence cancers.

Objective:To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD).Methods:It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton-Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.349.8) according to the quartile of PNI. Logistic regression analysis method was used to analyze the relationship between PNI and risk of functional dependence in MHD patients, and subgroup analysis was conducted. The receiver-operating characteristic (ROC) curve was used to assess the efficacy of PNI, serum albumin, and lymphocytes in predicting the risk of functional dependence in MHD patients.Results:A total of 206 MHD patients were included in this study, with age of (58.35±0.98) years old, and 132 (64.1%) males. There were 58 (28.2%) patients with diabetes, 179 (86.9%) patients with hypertension, and 36 (17.5%) patients with cardiovascular diseases. There were 95 (46.1%) patients developing functional dependence. Compared with normal functional status group, functional dependence group had higher age ( t=-6.87, P<0.001), proportion of diabetes ( χ2=6.58, P=0.010), and pulse pressure ( t=-3.17, P=0.002), and lower diastolic pressure ( t=3.88, P<0.001), serum creatinine ( t=3.44, P=0.001), serum albumin ( t=4.09, P<0.001) and PNI ( t=3.92, P<0.001). The incidence of functional dependence in PNI Q1 group (69.2%, 36/52) was significantly higher than those in Q2 group (49.0%, 25/51), Q3 group (34.0%, 18/53) and Q4 group (32.0%, 16/50), and the differences among groups were statistically significant (all P<0.05). Logistic regression analysis showed that after adjusting for confounding factors: age, diabetes, pulse pressure, and serum creatinine, the risk of functional dependence of PNI Q1 group was 3.217 folds higher than that in Q4 group ( OR=3.217, 95% CI 1.229-8.422, P=0.017). The risk probability model of PNI predicting the occurrence of functional dependence in MHD patients: logit (odds)=5.854-0.128 3×PNI. The area under the ROC curve ( AUC) for PNI predicting the risk of functional dependence in MHD patients was 0.66 (95% CI 0.58-0.73, P<0.001), slightly higher than that of serum albumin ( AUC=0.64, 95% CI 0.54-0.73, P<0.001). The optimal cutoff value of PNI predicting the occurrence of functional dependence was 46.15, with sensitivity of 72.07% and specificity of 57.89%. Conclusion:Low PNI is associated with high risk of functional dependence in MHD patients.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.
Humans ; Male ; Child ; Female ; Acoustic Stimulation ; Autistic Disorder/physiopathology* ; Arousal/physiology* ; Pupil/physiology* ; Habituation, Psychophysiologic/physiology* ; Auditory Perception ; Child, Preschool

Birth cohort study has played an important role in exploring the effect of exposures in early life on long-term health of offspring. With the rapid increase of problems of reproductive health among couples at childbearing age, the assisted reproductive technology (ART) has been widely introduced into clinical practice. However, the influences of ART on long-term outcomes of mothers and infants have not been fully studied. In 2016, the China National Birth Cohort (CNBC), a multicenter prospective cohort study recruiting families with ART-conceived pregnancies and spontaneous-conceived pregnancies simultaneously was launched officially. By June 30, 2021, a total of 72 000 families covering 39 000 ART- pregnancies and 33 000 spontaneous- pregnancies have been recruited in the study, their information and biological samples were collected at multiple time points, i.e., before assisted reproductive treatment, in embryo transfer period, in first, second and third trimesters, at delivery, and at 42 days after birth, 6 months, 1 year old and 3 years old. The main objectives of this study are to assess the development and health of offspring born after ART treatment, identify risk factors associated with adverse birth outcomes and childhood diseases and provide scientific basis for the strategies to improve the quality of new birth population. This paper will give a brief introduction to the establishment and research progress of CNBC.

Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (aHR=2.16, 95%CI:1.20-3.90) and 20-29 age group (aHR=5.48, 95%CI:2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (aHR=1.67, 95%CI:1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95%CI:1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.
Cohort Studies ; DNA, Viral ; Hepatitis B/epidemiology* ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/epidemiology* ; Humans ; Risk Factors ; Young Adult

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.
Child ; China ; Cough ; Edema ; Female ; Humans ; Male ; Mediastinal Neoplasms/diagnosis* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Sounds ; Retrospective Studies ; Superior Vena Cava Syndrome/therapy*

OBJECTIVE: To explore the influence of electroacupuncture (EA) on the expression of AMPA receptor subunit GluR1 in the rats with acute spinal cord injury (SCI) and explore the potential effect mechanism of EA in treatment of acute SCI. METHODS: A total of 80 SD rats were randomly divided into five groups, i.e. a sham-operation group, a model group, an AMPA antagonist (DNQX) group, an EA group and a DNQX+EA group, 16 rats in each group. The modified Allen's impacting method was adopted to prepare the rat model of acute SCI at T RESULTS: Compared to the sham-operation group in 6 h, 24 h and 48 h after modeling, the BBB scores were all significantly decreased in the model group ( CONCLUSION The intervention with EA at "Dazhui" and "Mingmen" promotes the repair of the injured nerve in the spinal anterior horn probably through inhibiting GluR1 expression in the spinal injured area in the rats with acute SCI.
Animals ; Electroacupuncture ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/genetics* ; Spinal Cord ; Spinal Cord Injuries/therapy*