Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Mice ; Animals ; Lip/innervation* ; Prospective Studies ; Mandibular Nerve/pathology* ; Sensation/physiology* ; Trigeminal Nerve Injuries/pathology*

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

Aim To investigate the effects of Dexmedetomidine(DEX)on HT22 cells with hypoxia/reoxygenation based on ferroptosis and the underlying mechanism.Methods HT22 cells were used to prepare H/R injury model.In order to investigate the optimal concentration of DEX, cells were divided into five groups: control group, H/R group, low concentration(H/R+DEX2.5, 2.5 μmol·L-1), medium concentration(H/R+DEX5, 5 μmol·L-1), high concentration(H/R+DEX10, 10 μmol·L-1)DEX intervention H/R group, and the survival rates of cells were detected by MTT assay.To investigate the mechanism of the protective effects on HT22 cells with H/R injury, HT22 cells were divided into four groups: control group, H/R group, H/R+DEX5 group, and H/R+DEX5 +ML385 group.The survival rates of cells were detected by MTT assay; the levels of Fe2+ were detected by FerroOrange fluorescent probe; the C11BODIPY581/591 was used to detect the change of lipid ROS on the cells; MDA and reduced glutathione kits were used to detect the content of MDA and GSH of cells respectively.The expressions of Nrf2, GPX4, TFR1 and SLC7A11 were detected by Western blot.Results Compared with control group, the survival rate of cells, the content of GSH, and the expression of Nrf2, GPX4 and SLC7A11 all significantly decreased(all P<0.05), the level of lipid ROS, the content of MDA, the level of Fe2+, and the expression of TFR1 all significantly increased in H/R group(all P<0.01).Compared with H/R group, the survival rate of cells, the content of GSH, and the expression of Nrf2, GPX4 and SLC7A11 significantly increased(all P<0.05), the level of lipid ROS, the content of MDA, the level of Fe2+, and the expression of TFR1 significantly decreased with the treatment of DEX(all P<0.05).Compared with H/R+DEX group, the survival rate of cells, the content of GSH, and the expression of Nrf2, GPX4 and SLC7A11 markedly decreased(all P<0.05), the lipid ROS, MDA and Fe2+, and the expression of TFR1 significantly increased in H/R+DEX+ML385 group(all P<0.05).Conclusions DEX can reduce H/R injury on HT22 cells by inhibiting ferroptosis, and the mechanism might be related to the promotive expression of Nrf2.

Objective:To analyze and compare the dosimetric differences based on volumetric-modulated arc therapy (VMAT), fixed field intensity-modulated radiotherapy (F_IMRT), and electron irradiation combined with VMAT (E&VMAT) in radiotherapy for breast cancer after modified mastectomy, aiming to provide reference for clinical selection of treatment plan.Methods:Ten patients with the left breast cancer who received radiotherapy after modified mastectomy were randomly selected. The target areas included chest wall and supraclavicular region, and the prescribed dose was 43.5 Gy in 15 fractions (2.9 Gy/F). Based on the Pinnacle 3 planning system, the VMAT, F_IMRT and E&VMAT plans (electron beam for chest wall, VMAT for supraclavicular area) were designed for each patient. The conformity and homogeneity of the target areas, the dose of organs at risk and treatment time were compared. Results:The VMAT plan could improve the dose distribution of the target areas. The conformity index and homogeneity index of the target dose were significantly better than those of the F_IMRT and E&VMAT plans (all P<0.05). The average dose, V 30Gy, V 20Gy, V 10Gy of the left lung in the VMAT plan were significantly better than those in the F_IMRT and E&VMAT plans (all P<0.05). The V 5Gy of the left lung in the VMAT plan was significantly better than that in the F_IMRT plan ( P<0.05). There was no statistical difference in the V 5Gy of the left lung between the VMAT and E&VMAT plans ( P>0.05). The heart, right breast and right lung of the VMAT plan could meet the clinical dose limit requirements. The treatment time of the VMAT, F_IMRT and E&VMAT plans was (326±27) s, (1 082±169) s, and (562±48) s, respectively. Conclusions:Compared with the F_IMRT and E&VMAT plans, the VMAT plan has better quality and shorter treatment time. VMAT plan has higher value in clinical application compared with the F_IMRT and E&VMAT plans.

OBJECTIVE: To investigate the protective effects of dexmedetomidine (DEX) against cerebral ischemia/reperfusion (I/R) injury in mice and its relation with mitochondrial fusion and fission. METHODS: Male ICR mice were randomly divided into sham-operated group, I/R group, I/R+DEX group and I/R+DEX+dorsomorphin group. Mouse models of cerebral I/R injury were established by modified thread occlusion of the middle cerebral artery. DEX (50 μg/kg) was injected intraperitoneally at 30 min before cerebral ischemia, which lasted for 1 h followed by reperfusion for 24 h. The neurobehavioral deficits of the mice were evaluated based on Longa's scores. The volume of cerebral infarction was detected by TTC staining. The changes in mitochondrial morphology of the brain cells were observed with transmission electron microscopy. Western blotting was performed to detect the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), mitochondrial fusion protein (Mfn2) and mitochondrial fission protein (p-Drp1) in the brain tissues. RESULTS: DEX pretreatment significantly reduced the neurobehavioral score and the percent volume of cerebral infarction in mice with cerebral I/R injury. Treatment with dorsomorphin (an AMPK inhibitor) in addition to DEX significantly increased the neurobehavioral score and the percent volume of cerebral infarction in the mouse models. Transmission electron microscopy showed that DEX obviously reduced mitochondrial damage caused by cerebral I/R injury and restored mitochondrial morphology of the brain cells, and such effects were abolished by dorsomorphin treatment. Western blotting showed that DEX pretreatment significantly increased the expressions of p-AMPK and Mfn2 protein and decreased the expression of p-Drp1 protein in the brain tissue of the mice, and these changes were also reversed by dorsomorphin treatment. CONCLUSIONS Preconditioning with DEX produces protective effects against cerebral I/R injury in mice possibly by activating AMPK signaling to regulate mitochondrial fusion and fission in the brain cells.
Animals ; Brain Ischemia ; Dexmedetomidine ; Male ; Mice ; Mice, Inbred ICR ; Mitochondrial Dynamics ; Reperfusion Injury

OBJECTIVE：To evaluate the benefit and risk of tirofiban in the treatment of acute coronary syndrome （ACS），and to provide evidence-based reference for clinical drug selection and decision. METHODS ：Retrieved from domestic and foreign database as PubMed ，the Cochrane Library ，CNKI and Wanfang database ，during the establishment of database to Apr. 2020，two researcher independently screened the literature based on inclusion and exclusion criteria and extracted the data. After the quality evaluation of the included literatures ，based on rapid health technology assessment ，the extracted results were classifiedly evaluated and comprehensively analyzed. RESULTS ：A total of 13 researches of systematic review/Meta-analysis and 1 research of pharmacoeconomics were included. Compared with placebo ，tirofiban could significantly reduce all-cause mortality [OR ＝0.68， 95％CI（0.54，0.86），P＝0.000 1] and the incidence of major adverse cardiac events （MACE）in patients with ACS [RR ＝0.24， 95％CI（0.14，0.40），P＜0.01]，and increased the incidence of TIMI 3 [OR＝5.73，95％CI（2.99.10.97），P＜0.01]. Tirofiban and eptifibatide had similar therapeutic efficacy in the treatment of ACS ，but tirofiban significantly increased the risk of TIMI small bleeding in patients with ACS [RR ＝0.61，95％CI（0.38，0.98），P＝0.04]. For ACS patients with non-ST elevation （NSTE-ACS）， compared with placbo ，tirofiban significantly reduced the incidence of MACE [RR ＝0.76，95％ CI（0.61，0.96），P＝0.018]，but significantly increased the risk of bleeding [OR ＝1.49，95％CI（1.12，1.98），P＝0.006]，while there was no significant difference in its effects on the all-cause mortality of NSTE-ACS patients （P＞0.05）. For STEMI patients ，compared with placebo ，tirofiban significantly reduced the all-cause mortality [RR＝0.61，95％CI（0.35，1.05），P＝0.007] and the incidence of MACE [RR ＝0.63，95％ CI（0.44，0.90），P＝0.007]. When combined with liposuction ，tirofiban also significantly reduced the incidence of MACE [RR ＝ 2.05，95％CI（1.71，2.46），P＜0.01]，and significantly increased the incidence of TIMI 3 [OR＝3.18，95％ CI（2.4，4.22），P＜ 0.01]，but there was no significant difference in its effects on bleeding risk （P＞0.05）. The included pharmacoeconomic study showed that patients treated with bivalutine could get 10.07 QALYs，patients treated with heparin combined with tirofiban could get 9.98 QALYs，and the incremental cost-effectiveness ratio bivalutine compared to the latter one was 28 575.77 yuan/QALYs，which was lower than 3 times of the per capita GDP of some cities. CONCLUSIONS ：Tirofiban has good efficacy in the treatment of ACS，but it can increase the risk of bleeding than eptifibatide and placebo. Domestic bivalirudin treating for ACS has a cost-effectiveness advantage over tirofiban combined with heparin.

Objective:To summarize the problems of nursing information system application in Special Ward and to explore the solutions.Methods:From January to February 2017, we summarized the problems of nursing information system application in Special Ward and analyzed the causes. From March 2017, we implemented the improvements, such as strengthening nursing training and quality control, working with doctors closely, improving the auditing ability to doctor's advice, double checking for doctor's advice, shift by words and building the ward oral drug registration. We compared the indexes of nursing quality before and after improvement.Results:After improvement, the time of daily computer operation by nurses reduced; the number of problematic doctor's advice found and corrected by nurses increased; the times of medication administration error prevention also increased; the differences were all statistical ( P<0.05) . Conclusions:Improvements for nursing information system of Special Ward effectively improve nurses' working efficiency, prevent and reduce the nursing errors.

Objective The IAEA report No.483 describes the latest method of small field dosimetry.The field output factor measurement and correction methods are used to improve the accuracy and consistency of the measurement results for different type detectors.Methods The field output factors from 0.6 cm×0.6 cm to 10 cm× 10 cm were measured using IBA's CC13 ionization chamber,CC01 ionization chamber,PFD semiconductor detector,EFD semiconductor detector and Razor semiconductor detector,respectively.The field output correction factors were used to correct the measurement result.Results Compared with the corrected data,the results of ionization chamber are mainly affected by the volume averaging and the fluence perturbation effect,lead to the measurement result which is 4.70％ lower at 0.6 cm × 0.6 cm;The results of Shielded semiconductors are mainly affected by fluence perturbation effect,lead to the measurement result which is 4.80％ higher at 0.6 cm × 0.6 cm.The results of unshielded semiconductors are mainly affected by energy response and fluence perturbation effect,resulting in lower measurement results at the field size＞0.8 cm×0.8 cm,2.10％ lower at field size of 1.5 cm× 1.5 cm,higher measurement results at field size＜0.8 cm×0.8 cm and 1.1％ higher at field size of 0.6 cm×0.6 cm.Before the correction,the measurement results from different types of detectors are quite different,average standard deviation is 0.016 6.After the correction,the difference among the detectors is significantly reduced,average standard deviation is 0.006 6.Conclusions For detectors such as ionization chambers and semiconductors,the field output correction factors can be used to correct the output factors of the small field to improve the accuracy and consistency of the measurement results.

Objective improve the accuracy of the measurement results by using the field output factor measurement method based on daisy-chaining.Methods The Varian Edge Accelerator 6 MV X-ray data were measured using the IBA CC13 ionization chamber, IBA CC01 ionization chamber, IBA Razor semiconductor detector , IBA EFD semiconductor detector and Gafchromic EBT 3 film , respectively. Results Compared with the daisy-chaining measurement method,the results obtained by the conventional measurement method using CC13 were smaller. The deviation value was 16. 71% in the 1 cm × 1 cm field. The measurement results in a larger field via CC01 were bigger with a deviation of 8. 39% in the 40 cm × 40 cm filed. The measurement results via Razor in a larger field were larger with a deviation of 9. 40% in the 40 cm × 40 cm field. The measurement results were similar between EFD and Razor with a deviation of 9. 14% in the 40 cm × 40 cm field. The results of the film measurement were equivalent to those obtained from the daisy-chaining method in a field of＞ 1 cm × 1 cm with a deviation within 1. 60%,whereas the deviation was increased to 3. 13% in the 1 cm× 1 cm field. The results were consistent with daisy-chaining measurement if the 3 cm × 3 cm or 4 cm × 4 cm fields were selected as the intermediate fields with the maximum deviation of 0. 29%. Conclusions For the detectors with changing response along with the field size,daisy-chaining measurement method can be utilized to extend the measurement range and improve the accuracy of the measurement results.