In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

Aim To investigate the protective effect of orcinol glucoside on dexamethasone(DEX)-induced osteoblast injury and its mechanism. Methods Primary osteoblasts were extracted from calvaria of neonatal mice and cultured in medium with DEX(1 μmol•L

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.
Humans ; Male ; Female ; Middle Aged ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis ; Prognosis ; Neuroendocrine Tumors/pathology* ; Carcinoma, Neuroendocrine/therapy* ; Neoplasm Staging ; Retrospective Studies

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVE: To compare the clinical efficacy of acupuncture with different frequencies in the treatment of patients with functional dyspepsia (FD). METHODS: A total of 90 patients with FD were randomly divided into a 3-time acupuncture treatment per week group (3-A group, 31 cases, 2 cases dropped off), a 1-time acupuncture treatment per week group (1-A group, 30 cases, 2 cases dropped off) and a control group (29 cases, 2 cases dropped off). In the two acupuncture groups, the acupoints were Zhongwan (CV 12) and bilateral Tianshu (ST 25), Neiguan (PC 6), Liangqiu (ST 34), Yanglingquan (GB 34), Zusanli (ST 36) and Taichong (LR 3), stimulated 3 times a week and once a week, respectively; and the treatment was given consecutively for 4 weeks. In the control group, no intervention was adopted, but the compensatory therapy was provided after the end of follow-up. The scores of the symptom index of dyspepsia (SID), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were compared among the 3 groups before treatment, after 4 weeks of treatment and in 4 and 8 weeks after treatment completion separately. The score of Nepean dyspepsia life quality index (NDLQI) was evaluated before treatment, after 2 and 4 weeks of treatment and in 4 and 8 weeks after treatment completion. RESULTS: After 4 weeks of treatment and in 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS were all reduced in the 3-A group and the 1-A group when compared with the scores before treatment (P<0.000 1, P<0.05). After 4 weeks of treatment, the scores of SID, SAS and SDS in the two acupuncture groups were lower than those in the control group (P<0.000 1). After 2 and 4 weeks of treatment, the increased values of NDLQI score in the two acupuncture groups were all higher than those in the control group (P<0.05). In 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS in the 3-A group were lower than those in the 1-A group (P<0.001, P<0.05), and the increased values of NDLQI score in the 3-A group were higher than those in the 1-A group (P<0.000 1). CONCLUSION Acupuncture given 3 times per week is superior to the treatment given once per week in the aspects of relieving the clinical symptoms, improving the quality of life and regulating the emotional state in patients with FD. This efficacy is persistent for 8 weeks after treatment completion.
Humans ; Dyspepsia/therapy* ; Quality of Life ; Acupuncture Therapy ; Acupuncture Points ; Emotions

OBJECTIVE: To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs). METHODS: We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC. RESULTS: Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram. CONCLUSION The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.
Humans ; Male ; Female ; Middle Aged ; Aged ; Nomograms ; Retrospective Studies ; Prognosis ; Neoplasm Staging ; Stomach Neoplasms/pathology*

OBJECTIVETo investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia.

METHODSThe expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival (OS) and progression-free survival (PFS) of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene, the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored.

RESULTSThe expression level of MLAA-34 gene was significantly up-regulated as compared with that of healthy volunteers, moreover this up-regulation was related with a C59T SNP site located in second exon of MLAA-34 gene, meanswhile this SNP site is affinitive to the well-known mdecular markers of AML, inclinding Fms-like tyrosine kinase (FLT-3) and DNA methyltransferase-3A(DNAMT3A). The AML-M5 patients with high expression of MLAA-34 gene poorly responded to chemotherapy, the AML-M5 patients with MLAA-34 C59T mulation had even more high expression of MLAA-34 gene and significantly short OS and PFS in comparison with those of patients without C59T mutation.

CONCLUSIONThe C59T mutation in MLAA-34 gene is a high risk factor for recurrence of AML, and may be a cadidate target for treatment of AML.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

Objective To investigate tlle efficacy of L-carnitine in patients with right-sided heart failure induced by pulmonary arterial hypertension(PAH).Methods A total of 66 pulmonary arterial hypertension patients(14 idiopathic,36 congenital heart disease associated and 16 connective-tissue disease associated PAH,WHO heart functional class Ⅲ,n=38 or IV,n=28)were enrolled in this study and divided into control group(26 cases)and L-carnitine group(40 cases).All patients received conventional treatment according to guideline for treatment of right-sided heart failure.The patients in L-carnitine group received 5 g/d L-carnitine intravenously for seven days.Six-minute walking distance,WHO heart functional class,physical examination,and serum markers were evaluated at baseline and 7 days after enrollment.Results Compared to the baseline,six-minute walking distance was significantly increased(75m vs.45 m,P＜0.05).WHO heart functional class significantly improved(impmved 2 classes in 16 patients,impmved 1 class in 13,no improved in 6,worsen in 5 vs.3,8,9,6 respectively in the control,P=0.04),BNP level significant decreased(58.16 ng/L vs.33.29 ng/L,P=0.01)and systolic blood pressure significantly increased[8.1 mm Hg vs.2.4 mm Hg(1 mm Hg=0.133 kPa),P=0.03]in Lcarnitine group compared with those in control group.No patient was withdrawn from this study for safety reasons.Conclusions L-carnitine could improve short-term exercise capacity and WHO heart functional class in right-sided heart failure patients induced by PAH.

Objectives To analyze the diagnostic value of electrocardiogram (ECG) in patients with pulmonary artery hypertension (PAH) confirmed by right-heart catheterization (RHC).Methods A total of 64 patients with suspected PAH[sPAP≥36 mm Hg(1 mm Hg =0.133 kPa) estimated by echocardiography]were enrolled in this study.All patients were examined by 12-lead ECG within half an hour before RHC.Results PAH was excluded in 26 patients and confirmed in 38 patients.ECG analysis showed that S amplitude＞0.21 mV in lead Ⅰ ,QRS axis＞87°,R_(v1) + S_(v5)＞0.76 mV were good parameters for diagnosing PAH with sensibility and specificity of 89%,81%;86%,92%;84%,83%,respectively.QRS axis was positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.75,P＜0.001),R_(v1) + S_(v5) was positively correlated with pulmonary vascular resistance (PVR) (r =0.74,P＜0.001),R_(v1) + S_(v5) and S amplitude in lead Ⅰ was negatively correlated with cardiac index (CI)(r = -0.62,P ＜0.001).Conclusion ECG combined with echocardiography are adequate screening tools to rule out the presence of PAH.QRS axis,R_(v1) + S_(v5) and S amplitude in lead Ⅰ were significantly correlated with hemodynamic parameters derived from RHC in PAH patients.