Multiple system atrophy (MSA) is a rare with its adult onset progressive neurodegenerative disease, which is clinically classified into parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes based on the presenting motor phenotype. MSA has an insidious onset, with its early manifestation of autonomic dysfunction so is easily misdiagnosed. Neurogenic orthostatic hypotension (nOH) is a key manifestation of chronic autonomic failure in primary neurodegenerative diseases, and is the most common autonomic dysfunction in patients with MSA. Currently, the treatments for nOH in patients with MSA are limited. In this case report, the rehabilitation method is shared for nOH in patients with MSA, which provides ideas for clinical treatment and rehabilitation of nOH in these patients.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To screen the independent influencing factors for gastrointestinal bleeding(GIB)in hospitalized patients with coronary heart disease(CHD)and to construct and validate a no-mogram prediction model.Methods A total of 440 CHD patients who developed GIB during hospi-talization were selected as GIB group,and another 320 CHD patients hospitalized in the department of cardiovascular medicine were randomly selected as non-GIB group.The clinical data of the two groups were analyzed and compared.Multivariate logistic regression analysis was used to screen the indepen-dentinfluencing factors for GIB.Based on these factors,a nomogram prediction model for the risk of GIB in hospitalized CHD patients was constructed.The entire dataset was randomly divided into train-ing set(n=532)and validation set(n=228)in a 7∶3 ratio.The performance of the nomogram model was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic regression analysis showed that body mass index(BMI),history of digestive system diseases,CHD classification,albumin,white blood cell count,monocyte-to-lymphocyte ratio(MLR),and low-density lipoprotein were all independent influencing factors for GIB in CHD patients(P＜0.05).ROC curve analysis indicated that the nomo-gram model(excluding low-density lipoprotein)constructed based on independent influencing factors exhibited good discrimination in both the training set(area under the curve:0.839,95％CI,0.805 to 0.873)and the validation set(area under the curve:0.810,95％CI,0.751 to 0.868).Calibration curve analysis demonstrated good consistency between the predicted probabilities and the observed incidence of GIB in hospitalized CHD patients in both the training and validation sets.DCA results revealed that the nomogram model had a good clinical net benefit.Conclusion The nomogram model constructed based on independent influencing factors has good predictive performance for the risk of GIB in hospitalized CHD patients and can provide a basis for clinicians to promptly identify GIB and adjust medication regimens.

Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.

Objective To investigate and analyze the association between serum microRNA-141-3p(miR-141-3p)and miR-223-3p levels and neonatal necrotizing enterocolitis.Methods Eighty neonates with necrotizing enterocolitis admitted to our hospital between January 2019 and January 2022 were enrolled as subjects.According to the disease stage,they were divided into the stage Ⅱ group(n=43)and the stage Ⅲ group(n=37).Additionally,80 healthy newborns born during the same period were recruited as the control group.General clinical data were collected and analyzed systematically.The expression levels of miR-141-3p and miR-223-3p were detected using quantitative real-time PCR(qRT-PCR).Spearman's correlation analysis was performed to evaluate the relationship between miR-141-3p,miR-223-3p,and the severity of the disease.Multivariate logistic regression analysis was conducted to assess the impact of miR-141-3p and miR-223-3p on the severity of pediatric illness.Furthermore,a Receiver Operating Characteristic(ROC)curve was plotted to determine the diagnostic value of miR-141-3p and miR-223-3p in predicting the severity of the patient's condition.Results Compared with the control group,the rela-tive expression levels of miR-141-3p and miR-223-3p in the diseased group were significantly decreased(P<0.05).Similarly,compared with the stage Ⅱ group,the relative expression levels of miR-141-3p and miR-223-3p in the stage Ⅲ group were also markedly reduced(P<0.05).Furthermore,miR-141-3p and miR-223-3p exhibited a nega-tive correlation with disease severity(r=-0.489,-0.496,P<0.05).Increased relative expression of miR-141-3p and miR-223-3p was identified as a protective factor influencing disease severity in children(P<0.05).The AUC values for diagnosing the severity of necrotizing enterocolitis using miR-141-3p,miR-223-3p,and their combination were 0.806,0.783,and 0.885,respectively.Combined diagnosis demonstrated significantly better performance than miR-141-3p alone(Z=2.050,P=0.040)or miR-223-3p alone(Z=2.184,P=0.029).Conclusion In neonates with necrotizing enterocolitis,the relative expression levels of serum miR-141-3p and miR-223-3p are significantly decreased,which are closely associated with disease progression and provide potential auxiliary diagnostic value for assessing disease severity.

Objective To investigate and analyze the association between serum microRNA-141-3p(miR-141-3p)and miR-223-3p levels and neonatal necrotizing enterocolitis.Methods Eighty neonates with necrotizing enterocolitis admitted to our hospital between January 2019 and January 2022 were enrolled as subjects.According to the disease stage,they were divided into the stage Ⅱ group(n=43)and the stage Ⅲ group(n=37).Additionally,80 healthy newborns born during the same period were recruited as the control group.General clinical data were collected and analyzed systematically.The expression levels of miR-141-3p and miR-223-3p were detected using quantitative real-time PCR(qRT-PCR).Spearman's correlation analysis was performed to evaluate the relationship between miR-141-3p,miR-223-3p,and the severity of the disease.Multivariate logistic regression analysis was conducted to assess the impact of miR-141-3p and miR-223-3p on the severity of pediatric illness.Furthermore,a Receiver Operating Characteristic(ROC)curve was plotted to determine the diagnostic value of miR-141-3p and miR-223-3p in predicting the severity of the patient's condition.Results Compared with the control group,the rela-tive expression levels of miR-141-3p and miR-223-3p in the diseased group were significantly decreased(P<0.05).Similarly,compared with the stage Ⅱ group,the relative expression levels of miR-141-3p and miR-223-3p in the stage Ⅲ group were also markedly reduced(P<0.05).Furthermore,miR-141-3p and miR-223-3p exhibited a nega-tive correlation with disease severity(r=-0.489,-0.496,P<0.05).Increased relative expression of miR-141-3p and miR-223-3p was identified as a protective factor influencing disease severity in children(P<0.05).The AUC values for diagnosing the severity of necrotizing enterocolitis using miR-141-3p,miR-223-3p,and their combination were 0.806,0.783,and 0.885,respectively.Combined diagnosis demonstrated significantly better performance than miR-141-3p alone(Z=2.050,P=0.040)or miR-223-3p alone(Z=2.184,P=0.029).Conclusion In neonates with necrotizing enterocolitis,the relative expression levels of serum miR-141-3p and miR-223-3p are significantly decreased,which are closely associated with disease progression and provide potential auxiliary diagnostic value for assessing disease severity.

Objective:To evaluate the clinical efficacy and the mid- and long-term follow-up outcomes of transanal anaplasty for treating rectovestibular fistula.Methods:The clinical data of 68 female infants diagnosed with rectovestibular fistula undergoing transanal anoplasty at the Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from Oct 2014 to Dec 2023 was collected. Postoperative complications, perineal and anal appearances, and defecation function of postoperative children aged 3 years or older were recorded.Results:After surgery 68 children followed-up for 6 months of recent with short-term complications in 6 cases, including 3 cases of incision infection, 2 cases of rectal mucosal prolapse, and 1 case of anal stenosis. Rintala score was (18.65±1.99). Twenty-five children underwent anorectal manometry, no significant differences were observed in the maximal systolic pressure of the anal canal( t=-0.596, P=0.563) and the maximum systolic time( t=-0.183, P=0.854). The resting pressure( t=-3.050, P=0.005), functional length( t=2.696, P=0.012), and positive rate of rectal anal inhibitory reflex( χ2=6.382, P=0.012) of the anal canal were significantly lower than those of the normal group( P<0.05). Conclusions:Transanal anaplasty for the treatment of rectovestibular fistula in girls has a low incidence of complications. It results in a normal perineal body appearance, good anal bowel control, and high quality of life.

Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Objective To explore the therapeutic mechanism of Liuwei Buqi(LWBQ)Formula for chronic obstructive pulmonary disease(COPD)in rat models.Methods SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide(LPS)instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks,starting at the 5th week of modeling.After the treatments,the rats were examined for lung pathologies,lung function,total cell count and white blood cell count in bronchoalveolar lavage fluid(BALF),and serum levels of IL-6,TNF-α,IL-18 and NO.The mRNA expressions of NLRP3,ASC,caspase-1,GSDMD-N,IL-1β,and IL-18 in the lung tissue were detected with qRT-PCR.Results Compared with the normal control rats,the COPD rat models had severe lung pathologies and showed significantly decreased lung function,increased total cell and leukocyte subset counts in BALF,and increased serum levels of IL-6,TNF-α,IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue.Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function,reduced total cell and leukocyte counts in BALF,and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue.The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference,but BALF cell counts,serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment.Conclusion LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.

Objective To explore the therapeutic mechanism of Liuwei Buqi(LWBQ)Formula for chronic obstructive pulmonary disease(COPD)in rat models.Methods SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide(LPS)instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks,starting at the 5th week of modeling.After the treatments,the rats were examined for lung pathologies,lung function,total cell count and white blood cell count in bronchoalveolar lavage fluid(BALF),and serum levels of IL-6,TNF-α,IL-18 and NO.The mRNA expressions of NLRP3,ASC,caspase-1,GSDMD-N,IL-1β,and IL-18 in the lung tissue were detected with qRT-PCR.Results Compared with the normal control rats,the COPD rat models had severe lung pathologies and showed significantly decreased lung function,increased total cell and leukocyte subset counts in BALF,and increased serum levels of IL-6,TNF-α,IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue.Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function,reduced total cell and leukocyte counts in BALF,and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue.The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference,but BALF cell counts,serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment.Conclusion LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.