Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies

At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.
Animals ; Apoptosis ; Cell Line, Tumor ; Diterpenes, Abietane ; Endoplasmic Reticulum Stress ; Humans ; Lung Neoplasms ; Mice ; Signal Transduction

Objective To summarize the experience of transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis (AS) with VENUS-A valve. Methods Retrospectively collected and analyzed the baseline characteristics,preoperative assessment, surgery details,early and mid-term clinical outcome of 10 patients who underwent TAVI. Results From April 2016 to April 2017,10 patients with severe AS were treated with TAVI at the Guangdong General Hospital. The median age was 75 (65,81)years old and 5(5/10)were males. The median Society of Thoracic Surgery score was 5% (2%,11%). TAVI was successful in 10 patients (10/10),and percutaneous coronary intervention was performed in two cases (2/10) at the same time. The median operation time was 190 (150,225) minutes,the ICU monitoring time was 113 (49, 231) hours,and the hospital stay was 12 (6,25) days. After the procedure,the mean aortic-valve gradient reduced to 10(6,21)mmHg(1 mmHg=0.133 kPa). There was minimal or mild marginal periprosthetic leak in five patients(5/10)and moderate leak in one patient(1/10). During the 30 days of follow up,one patient(1/10)die due to perioperative myocardial infarction and ventricular fibrillation. One patient(1/10)was implanted with a permanent pacemaker for severe arrhythmia. Two patients(2/10)occurred vascular complications. The median follow-up was 3(1,15)months. One patient had syncope at 6 months post operation with R-R interval up to 7 seconds and he was implanted with a permanent pacemaker. There was no death,stroke,surgical surgery intervention and rehospitallization due to heart failure during the follow up. Conclusions It is feasible,safe and effective to use VENUS-A valve for TAVI treatment in serve AS.

OBJECTIVETo explore possible mechanism of electroacupuncture (EA) for regulating immune function in anxiety disorder (AD) rats by observing the effect of acupuncture on the histology of thymus and expressions of atrial natriuretic peptide (ANP) and natriuretic peptide receptor type A (NPR- A) in thymus.

METHODSTotally 34 SD healthy rats were randomly divided into the blank control group (n = 10), the model group (n = 12), the EA group (n = 12). Anxiety model was established in rats of the model group and the EA group by using chronic unpredictable stress (CUS) stimulation. EA (15/25 Hz) at Neiguan (PC6) and Shenmen (HT7) was performed in the EA group, with 15-min needle retaining, once every other day, 15 days in total. Needle was fixed at same acupoints for 15 min without electric stimulus in the other two groups. Anxiety-like behavior was measured by elevated plus-maze (EPM) test. Pathological changes of thymus tissue were observed by optical microscope. Expressions of ANP and NPR-A in thymus were measured by immunohistochemical assay.

RESULTSThe thymus tissue in the model group was severely atrophied, with unclear structure of thymic lobules, unclear margin of thymic medulla, loosely arranged lymphocytes ,and obviously enlarged volume of thymic corpuscle. The thymus tissue in the EA group was mildly atrophied, with existent structure of thymic lobules, clear margin of thymic medulla, densely arranged lymphocytes in cortical region, and widened medullary area. Com- pared with the blank control group, the percentage of open-arms entries (OE%) in the total QE times ob- viously decreased in the model group (P < 0.05), ANP expression obviously increased (P < 0.05), and NPR-A expression obviously decreased (P < 0.01). Compared with the model group, OE% was obviously elevated (P < 0.05), ANP expression obviously decreased (P < 0.05), and NPR-A expression obviously increased (P < 0.01) in the EA group.

CONCLUSIONEA not only could reduce anxiety of rats, but also could improve chronic stress induced thymus injury through intervening synthesis and secretion of ANP, as well as the expression of NPR-A (a specific receptor of ANP).

Acupuncture Points ; Animals ; Anxiety Disorders ; therapy ; Atrial Natriuretic Factor ; metabolism ; Electroacupuncture ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism ; Thymus Gland ; pathology

Androgen receptor (AR) plays an important role in the maintenance of prostate function and development of prostate cancer. AR is the key target in the therapy of prostate cancer. In this study, a cell-based screening assay was established by dual-luciferase reporter system to analyze the activity of AR. In the screening assay, we detected the anti-prostate cancer activities of rhodiola root extract, wild kiwifruit root extract and tripterygium wilfordii root extract, which may provide a new strategy for the treatment of prostate cancer.

BACKGROUNDJoint line (JL) is a very important factor for total knee arthroplasty (TKA) to restore. The objective of this study was to evaluate the early clinical and kinematic results of TKAs with posterior-stabilized (PS) or cruciate retaining (CR) implants in which the JL was elevated postoperatively.

METHODSData were collected from patients who underwent TKA in our department between April 2011 and April 2014. The patients were divided into two groups based on the prosthesis they received (PS or CR). At 1-year postoperatively, clinical outcomes were evaluated by the American Knee Society (AKS) knee score, AKS function score, and patella score. In vivo kinematic analysis after TKA was performed on all patients and a previously validated three-dimensional to two-dimensional image registration technique was used to obtain the kinematic data. Anteroposterior (AP) translation of the medial and lateral femoral condyles, and axial rotation relative to the tibial plateau, were analyzed. The data were assessed using the Mann-Whitney test.

RESULTSAt time of follow-up, there were differences in the AKS knee scores (P = 0.005), AKS function scores (P = 0.025), patella scores (P = 0.015), and postoperative range of motions (P = 0.004) between the PS group and the CR group. In the PS group, the magnitude of AP translation for the medial and lateral condyle was 4.9 ± 3.0 mm and 12.8 ± 3.3 mm, respectively. Axial rotation of the tibial component relative to the femoral component was 12.9 ± 4.5°. In the CR group, the magnitude of AP translation for the medial and lateral condyle was 4.3 ± 3.5 mm and 7.9 ± 4.2 mm, respectively. The axial rotation was 6.7 ± 5.9°. There were statistically different between PS group and CR group in kinematics postoperatively.

CONCLUSIONOur results demonstrate that postoperative JL elevation had more adverse effects on the clinical and kinematic outcomes of CR TKAs than PS TKAs.

Aged ; Arthroplasty, Replacement, Knee ; methods ; Biomechanical Phenomena ; Female ; Humans ; Knee Joint ; surgery ; Male ; Middle Aged ; Postoperative Period ; Treatment Outcome

OBJECTIVETo evaluated the manganese (Mn), cobalt (Co) and molybdenum (Mo) levels in blood and urine among general population in China, and thereby to analyze their prevalent features.

METHODSFrom 2009 to 2010, a total of 18 120 subjects of general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and their blood and urine samples were also collected.Inductive coupled plasma mass spectrometry (ICP-MS) was applied to test the Mn, Co and Mo levels of blood and urine samples, and the Mn, Co, Mo distribution in blood and urine among groups of population in different ages and genders were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Mn concentration in blood was 8.98 µg/L. The Mn concentration in blood among males and females were separately 8.14 µg/L and 9.88 µg/L (Z = -18.84, P < 0.01). The GM of Mn concentration in urine was 0.63 µg/L. The Mn concentration in urine among males and females were separately 0.62 µg/L and 0.63 µg/L (Z = -0.67, P > 0.05). The geometric mean (GM) of Co concentration in blood was 0.194 µg/L. The Co concentration in blood among males and females were separately 0.166 µg/L and 0.225 µg/L (Z = -23.04, P < 0.01). The GM of Co concentration in urine was 0.282 µg/L. The Co concentration in urine among males and females were separately 0.260 µg/L and 0.307 µg/L (Z = -7.35, P < 0.01). The GM of Mo concentration in blood was 0.25 µg/L. The Mo concentration in blood among male and female group were separately 0.27 µg/L and 0.23 µg/L (Z = -5.03, P < 0.01). The GM of Mo concentration in urine was 27.7 µg/L. The Mo concentration in urine among males and females were 29.8 µg/L and 25.6 µg/L (Z = -6.31, P < 0.01), respectively.

CONCLUSIONThe Mn, Co and Mo levels in blood and urine varied by gender and area among general population in China, the study provided basic data evidence for the following Mn, Co and Mo biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cobalt ; Environmental Exposure ; Environmental Monitoring ; Female ; Humans ; Male ; Manganese ; Middle Aged ; Molybdenum