Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

OBJECTIVE To explore the current status and safety of medication in pregnant patients, and explore the working mode and data accumulation of the pregnancy medication consultation clinic. METHODS All pregnant women who received consultations at the Pregnancy and Lactation Medication Consultation Clinic of the First Affiliated Hospital of Zhejiang University School of Medicine from October 2021 to December 2022 were selected as the study subjects. Their names, ages, contact information, last menstrual period, and medication use during pregnancy were recorded, and the medication profile and safety of the study population were evaluated. Organized the intervention measures of clinical pharmacists and conducted follow-up studies on their pregnancy outcomes. RESULTS A total of 179 consultation pregnant women were included, and 80% of the patients in the study population used drugs in the unknown pregnancy state, with 3 drugs per capita. The most common reason for drug use was upper respiratory tract infection. The three types of drugs with the highest use rate were traditional Chinese patent medicines, antibacterial drugs, antipyretic and analgesic drugs. The usage rate of B-grade drugs in the study population was the highest, accounting for 51.3%; 8.4% of patients used X-grade medication. One hundred and fifty-one cases were followed up, with a loss of follow-up rate of 15.6%. The recommended acceptance rate of drug risk assessment given by pharmacists for patients was 95.4%. There were 98.7% of patients believe that pregnancy counseling clinics were helpful and could effectively alleviate anxiety. CONCLUSION Pregnancy medication consultation clinics can provide patients with scientific and personalized medication guidance and popular science education, and have significant effects in alleviating anxiety and depression in pregnant women.

As the most common endocrine malignant tumor,the incidence rate of thyroid cancer is increasing year by year.However,the vast majority of subtypes have a good prognosis after traditional surgery,TSH suppression therapy and 131I treatment.With the progressive development of modern medicine,for a few thyroid cancers with poor effects of traditional treatment,molecular diagnosis and targeted therapy have further enriched the therapeutic means of thyroid cancer,in which BRAF mutation is widely present in thyroid cancer,but it often shows primary resistance or poor response to 131I therapy.The factors leading to primary or secondary resistance to targeted drugs with BRAF mutation may include genomic instability,expansion of resistant clones,occurrence of intrinsic mutations,or novel genetic and epigenetic alterations.In this article,we will review the research progress in targeted therapy resistance in BRAF-mutant thyroid cancer.

Objective:To establish the urodynamic classification of middle-aged and elderly men with benign prostatic obstruction(BPO), and to analyze the efficacy of transurethral resection of the prostate(TURP) on various types of patients.Methods:A retrospective analysis of middle-aged and elderly male patients with non-neurogenic lower urinary tract symptoms(LUTS) who underwent urodynamic tests from January 2010 to December 2018, including 793 patients with BPO. Urodynamics examination of detrusor without contraction needs to complete cystoscopy to diagnose BPO. During urodynamic examination, the detrusor uninhibited contraction induced by spontaneous or stimulation during the bladder filling period is diagnosed as overactivity of the bladder detrusor(DO), and the LinPURR chart indicates the detrusor underactivity(DU). Based on the persistence of BPO leading to DO, DU, and decreased bladder compliance, 793 male patients with BPO with LUTS were divided into four types, including type Ⅰ(BPO: n=164, 20.7%), type Ⅱ(BPO combined with DO: n=333, 42.00%), type Ⅲ(BPO combined with DU: n=267, 33.7%), type Ⅳ(BPO combined with decreased bladder compliance: n=29, 3.7%). The preoperative comparison between groups showed that the age of type Ⅰ-Ⅳ gradually increased, and the age of type Ⅰ was significantly smaller than other types [(67.3±8.2)years, (69.7±7.7)years, (71.5±7.9)years, (72.4±7.1)years, P<0.05]. Compared with other types, the type Ⅰ’s IPSS-S[(9.1±3.6)points vs.(10.4±3.1) points, (9.2±3.3) points, (10.4±3.1)points, P<0.05], IPSS-V[(13.5±3.4) points vs. (14.2±3.5)points, (14.0±3.5)points, (14.2±2.9)points, P<0.05], IPSS scores[(22.6±5.4)points, (24.7±4.9)points, (23.1±5.3)points, (24.6±4.7)points, P<0.05] were significantly lower than other groups, the maximum bladder capacity [(332.6±83.2)ml vs.(221.4±80.8)ml, (286.7±108.2)ml, (242.3±103.4)ml, P<0.05], the functional bladder capacity was significantly higher than other types[(215.2±90.0)ml, (148.5±76.0)ml, (154.9±87.2)ml, (121.2±72.9)ml, P<0.05]. Type Ⅱ’s IPSS-S[(10.4±3.1)points vs.(9.1±3.6)points, (9.2±3.3)points, P<0.05], nocturia frequency[(3.7±1.8)times vs.(3.2±1.8)times, (3.2±1.6)times, P<0.05], IPSS score[(24.7±4.9)points vs.(22.6±5.4)points, (23.1±5.3)points, P<0.05], quality of life scores [(4.9±0.9) points, (4.6±0.9)points, (4.6±0.9)points, P<0.05] was significantly higher than type Ⅰ and type Ⅲ ( P<0.05). Type Ⅲ and Ⅳ had higher residual urine than type Ⅱ[(121.3±96.4)ml, (121.3±96.4)ml vs.(71.2±73.5)ml, P<0.05]. Type Ⅳ’s IPSS-S[(10.4±3.1)points vs. (9.1±3.6)points, (9.2±3.3)points, P<0.05], IPSS-V[(14.2±2.9) points vs.(13.5±3.4)points, (14.0±3.5)points, P<0.05], the frequency of nocturia[(3.8±1.9)times vs.(3.2±1.8)times, (3.2±1.6)times, P<0.05] was significantly higher than that of type Ⅰ and type Ⅲ, and the quality of life score was higher than type Ⅰ and type Ⅲ[(4.3±0.8)points vs.(4.7±0.9)points, (4.6±0.9)points, P<0.05]. type Ⅱ and type Ⅳ’s bladder compliance[(21.4±24.2)ml/cmH 2O, (11.0±11.4)ml/cmH 2O vs.(33.9±23.7)ml/cmH 2O, (33.1±32.7)ml/cmH 2O, P<0.05], maximum bladder capacity[(221.4±80.8)ml, (242.3±103.4)ml vs.(332.6±83.2)ml, (286.7±108.2)ml, P<0.05], functional bladder capacity[(148.5±76.0)ml, (121.2±72.9)ml vs.(215.2±90.0)ml, (154.9±87.2)ml, P<0.05] were significantly less than type Ⅰ and type Ⅲ( P<0.05). From November 2016 to November 2018, 60 middle-aged and elderly male patients with confirmed BPO and TURP were selected, including type Ⅰ( n=17, 28.3%), type Ⅱ ( n=23, 38.3%), and Ⅲ type ( n=11, 18.3%), Ⅳ type( n=9, 15.1%). Type IV patients are significantly older than other types ( P<0.05), bladder compliance is significantly worse than other types( P<0.05), the maximum bladder capacity is smaller than other types( P<0.05). The follow-up started 3 months after the operation. The content of the follow-up included IPSS, IPSS-S, IPSS-V, nocturia frequency, undisturbed sleep time, nocturia quality of life score, and life quality score. Results:The IPSS scores of type Ⅰ, type Ⅱ, and type Ⅲ after TURP were significantly improved compared with preoperative(19.8±6.2 vs.3.4±1.8; 21.9±5.2 vs.4.6±2.6; 21.5±6.2 vs.5.7±4.6, P<0.05), type Ⅳ urine storage symptom score (9.1±4.1 vs.4.3±3.7), nocturia frequency(3.6±1.5vs.2.3±1.6), nocturia quality of life score (25.3±6.9 vs.31.4±13.7) Compared with preoperatively, there was no significant improvement( P>0.05). The quality of life score improvement of type Ⅳ patients was significantly lower than that of type Ⅰ, type Ⅱ, and type Ⅲ (10.9±9.1 vs.12.2±9.0, 14.4±5.7, 12.7±5.8, P<0.05). The IPSS score of type Ⅳ patients was significantly higher than that of type Ⅰ(7.0±5.8 vs.3.4±1.8), and the nocturia quality of life score was significantly lower than that of each group (31.4±13.7 vs.37.5±4.2, 38.7±3.5, 37.8±3.8, P<0.05). Conclusions:For middle-aged and elderly men with BPO, we divide them into four types based on the results of urodynamic examinations, type Ⅰ(simple BPO), type Ⅱ(BPO combined with DO), type Ⅲ(BPO combined with DU), type Ⅳ(BPO combined with bladder compliance decline). Type Ⅰ patients have the best bladder function, and TURP has the best effect; type Ⅱ has a high symptom score and poor quality of life, and can benefit after TURP; type Ⅲ bladder function is poor, and surgery should be performed as soon as possible to prevent further deterioration of bladder function; type Ⅳ bladder function is the best poor, IPSS score and quality of life score are high, TURP surgery is not effective.

In order to solve the problem that the early onset of paroxysmal atrial fibrillation is very short and difficult to detect, a detection algorithm based on sparse coding of Riemannian manifolds is proposed. The proposed method takes into account that the nonlinear manifold geometry is closer to the real feature space structure, and the computational covariance matrix is used to characterize the heart rate variability (RR interval variation), so that the data is in the Riemannian manifold space. Sparse coding is applied to the manifold, and each covariance matrix is represented as a sparse linear combination of Riemann dictionary atoms. The sparse reconstruction loss is defined by the affine invariant Riemannian metric, and the Riemann dictionary is learned by iterative method. Compared with the existing methods, this method used shorter heart rate variability signal, the calculation was simple and had no dependence on the parameters, and the better prediction accuracy was obtained. The final classification on MIT-BIH AF database resulted in a sensitivity of 99.34%, a specificity of 95.41% and an accuracy of 97.45%. At the same time, a specificity of 95.18% was realized in MIT-BIH NSR database. The high precision paroxysmal atrial fibrillation detection algorithm proposed in this paper has a potential application prospect in the long-term monitoring of wearable devices.
Algorithms ; Atrial Fibrillation ; Databases, Factual ; Electrocardiography ; Humans ; Wearable Electronic Devices

Objective To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and hemoglobinto-white blood cell ratio (HWR) prior to treatment in prognosis of non-operative esophageal squamous cell carcinoma (ESCC) patients.Methods From October 2009 to November 2014,a total of 362 non-operative ESCC patients were enrolled in this prospective study.x2 test was used to analyze the relationship between NLR,HWR and general clinical features;Univariate and multivariate Cox regression analysis was performed to evaluate the association between variables and prognosis of non-operative ESCC patients.Results The optimal cutoff level of 1.23 for NLR and 24.92 for HWR were identified by X-title software.x2 test indicated NLR was significantly associated with gender,tumor length,T stage,TNM stage and fasting blood glucose level.Moreover,univariate and multivariate analyses showed that high NLR and high HWR were all associated with a poor prognosis in non-operative ESCC.However,when patients were specifically stratified by treatment modus,subset analysis showed that NLR was only predictive of prognosis in the concurrent chemoradiotherapy group (HR =4.080,95％ CI:1.074-15.497,P =0.039),whereas the influence of HWR on prognosis was just existed in the sequential chemoradiotherapy group (HR =2.625,95％ CI:1.311-5.254,P =0.006).Conclusions In this investigation,we found that high NLR and high HWR were associated with poor prognosis in non-operative ESCC.

Objective To observe the effect ofGuanxin-Shutongcapsule in the treatment of arterial elasticity on patients with hypertension.Methods The hypertension patients who met the inclusion criteria were divided into treatment group (50 cases) and control group (52 cases). The control group was treated with antihypertensive drugs to control blood pressure within the normal range. The treatment group was treated withGuanxin-Shutongcapsule on the basis of the control group. All were given 8 weeks treatment. The main artery elastic parameters were meansured by the carotid-femoral pulse wave velocity (C-FPWV) and cervical-dorsal arterial pulse wave velocity (C-DPWV). The immune turbidimetric method was employed to enhance for the determination of high sensitive C reactive protein (hs-CRP); and radioimmunoassay was used to assess the serum IL-6, TNF-a, triglyceride (TG) and total cholesterol (TC). The blood pressure was monitored during the treatment.Results After the treatment, the level of hs-CRP (2.83 ± 1.35 mg/Lvs. 3.65 ± 1.38 mg/L,t=6.357), TNF-α (0.16 ± 0.08 mg/Lvs. 0.28 ± 0.07 mg/L,t=18.213), C-FPWV (13.85 ± 1.86 m/svs. 15.34 ± 1.78 m/s,t=6.524), C-DPWV (11.98 ± 1.45 m/svs. 12.87 ± 1.48 m/s,t=7.152) in treatment group was significantly lower than those in the control group (P<0.01).ConclusionGuanxin-Shutong capsule by inhibiting systemic inflammation, reducing and reversing atherosclerosis, and improving the arterial elasticity and blood pressure.

AIM:To investigate the RNA oxidative damage in human gastric cancer tissue and para-carcinoma tissue for exploring the role of RNA oxidation in the occurrence of gastric cancer .METHODS:Immunohistochemical ob-servation and LC-MS/MS analysis were performed in 61 cases of gastric carcinoma .The position and concentration of 8-oxoguanosine ( 8-oxoGsn ) were detected , respectively . RESULTS: The results of immunohistochemical observation showed that 8-oxoGsn was obviously up-regulated in the gastric cancer .The positive staining mainly accumulated in the cy-toplasm of the tumor cells .The results of mass spectrometry showed that the level of 8-oxoGsn in the gastric cancer tissues was higher than that in the para-carcinoma tissues (P<0.05).CONCLUSION:8-oxoGsn is up-regulated in gastric canc-er.RNA oxidative damage may play important roles in the occurrence of gastric cancer .