In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective:To evaluate the diagnostic accuracy of the convolutional neural network（CNN） in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment （P=0.282, P=0.085）. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinoma（P=0.382）. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.
Humans ; Nasopharyngeal Carcinoma ; Narrow Band Imaging ; China ; Neural Networks, Computer ; Nasopharyngeal Neoplasms/diagnostic imaging*

Objective Total knee arthroplasty is one of the most common orthopedic surgeries. Readmission due to severe complications after total knee arthroplasty is a grave concern to surgeons. In this study, we evaluated the risk factors for severe complications after primary total knee arthroplasty. Methods We retrospectively collected clinical data of 2,974 patients who underwent primary total knee arthroplasty from July 2013 to June 2019 in our hospital. Postoperative complication ≥ grade Ⅲ was defined as severe complication according to Clavien-Dindo classification system. Binary logistic regression was used to identify the predictive risk factors for severe complications. Results The complication rate after primary total knee arthroplasty was 6.8% and severe complication rate was 2.5%. Male (OR = 2.178, 95%CI: 1.324-3.585, P= 0.002), individuals above 75 years old (OR = 1.936, 95%CI: 1.155-3.244, P= 0.012), arrhythmia (OR = 2.913, 95%CI: 1.350-6.285, P= 0.006) and cerebrovascular disease (OR = 2.804, 95%CI: 1.432-5.489, P= 0.003) were predictive risk factors for severe complications after primary total knee arthroplasty. Conclusion Advanced age, male, arrhythmia, and cerebrovascular disease might be patients-related risk factors for postoperative severe complications after primary total knee arthroplasty. Special attention should be paid to patients with risk factors.
Humans ; Male ; Aged ; Arthroplasty, Replacement, Knee/methods* ; Comorbidity ; Retrospective Studies ; Risk Factors ; Postoperative Complications/etiology* ; Arthroplasty, Replacement, Hip/adverse effects*

Objective:To explore the clinical application value of sound touch elastography (STE) in the evaluation of the curative effect of acupuncture and moxibustion in the treatment of stroke patients with upper limb spasm.Methods:Fifty-five patients with upper limb spasm after stroke were selected as stroke group, and thirty healthy volunteers matched with age, gender and body mass index (BMI) were selected as control group between September 2020 and March 2021. The shear wave velocity (SWV) of biceps brachii and triceps brachii were measured in both groups. In stroke group, the SWVs of biceps brachii and triceps brachii on spastic side and non-spastic side were measured before and after acupuncture treatment, and the correlations between SWV and spastic grade (X), muscle response angle (R1), passive range of motion (R2), spastic angle (R2-R1) of modified Tardieu scale (MTS) were analyzed.Results:At 0 degree, the SWV of spastic biceps brachii (3.85±0.62)m/s was significantly higher than those of the non-spastic side [(3.34±0.35)m/s] and control group [(3.15±2.66)m/s] (all P<0.001), and decreased [ (3.45±0.47)m/s] after acupuncture treatment ( P<0.001). At 90 degree, the SWV of non-spastic biceps brachii was larger than those of spastic side and control group [1.98(1.92, 2.14)m/s vs 1.98(1.92, 2.11) m/s, 1.95(1.86, 2.05)m/s, all P<0.05], and there was no significant difference between the SWV of spastic side and control group ( P>0.05). There were no significant differences in SWV of triceps brachii between the spastic side and control group at both 0 degree or 90 degree ( P>0.05). At 0 degree, SWV positively correlated with MTS (x) ( rs=0.639, P<0.001) and negatively with R1 ( rs=-0.527, P<0.001) and R2 ( rs=-0.825, P<0.001) on the spastic biceps brachii. Conclusions:STE can provide quantitative index for the objective evaluation of the curative effect of acupuncture in upper limb spasm after stroke, and it is proposed to be an effective means of clinical diagnosis and efficacy evaluation in patients with upper limb spasm after stroke.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg(d. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Houttuynia ; chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inflammation ; drug therapy ; pathology ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Intestinal Mucosa ; drug effects ; metabolism ; microbiology ; pathology ; Lung ; drug effects ; metabolism ; pathology ; Male ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; pathology ; physiopathology ; Plant Extracts ; chemistry ; Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Toll-Like Receptors ; metabolism ; Zonula Occludens-1 Protein ; metabolism

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
alpha-Synuclein ; Humans ; Multiple System Atrophy ; Parkinson Disease ; ROC Curve ; Supranuclear Palsy, Progressive

Purpose To investigate the expression of sphingosine-1 phosphate receptor 1 (S1PR1) and sphingosine-1 phosphate receptor 4 (SIPR4) in triple negative breast carcinoma (TNBC) and to evaluate its correlation with the clinicopathologic features of TNBC. Methods 72 cases of tissue slides of TNBC were stained immunohistochemically and analyzed with image processing to calculate the S1PR1 and S1PR4 expression. Correlations of the S1PR1 and S1PR4 expression with the clinicopathologic features of TNBC were studied. Results Ki-67 index of high, moderate and low expression of the S1PR1 in TNBC were 48.89％, 36.11％ and 26.48％, respectively. The difference among them was significance (P＜0.001). Ki-67 index of high, moderate and low expression of the S1PR4 in TNBC were42.83％, 31.43％ and 28.93％, respectively. The difference among them was significance (P = 0.007 ). The positive rate of lymph node of high, moderate and low expression of the SI PR1 in TNBC were 31.4％, 48.6％ and 20.0％, respectively. The difference among them was significance (P = 0.012). The positive rate of lymph node of high, moderate and low expression of the S1PR4 in TNBC were 54.3％, 40.0％ and 5.7％, respectively. The difference among them was significance (P=0.010). The CD68 positive rate of high, moderate and low expression of the S1PR1 in TNBC were 47.22％, 42.59％ and31.48％, respectively. The difference among them was significance (P = 0.036). Both the difference of survive rate among high, moderate and low expression of the S1PR1 and S1PR4 were not significance (P = 0.209 and P =0.593 ). Conclusion High expression of S1PR1 and S1PR4 may contribute to the cellular proliferation and lymph node metastases in TNBC. The survive rate of TNBC maybe not related with both the S1PR1 and S1PR4 expression.