Carbapenem-resistant Enterobacteriaceae(CRE), one of the most urgent pathogens threatening human health worldwide, has posed a great challenge to clinical treatment. However, the imbalance between the lag in antibiotic research and development and the increase of CRE resistance has led to a "death threat" for patients infected with CRE, and it is urgent to explore new mechanisms of CRE resistance, which is closely related to the role of resistance genes, carbapenemases and efflux pumps. In addition, penicillin-binding protein, biofilms and iron carriers are expected to provide new research ideas to understand the drug resistance mechanism. The aim of this review is to summarize the mechanisms of CRE resistance and to provide new ideas for its treatment.

Carbapenem-resistant Enterobacteriaceae(CRE), one of the most urgent pathogens threatening human health worldwide, has posed a great challenge to clinical treatment. However, the imbalance between the lag in antibiotic research and development and the increase of CRE resistance has led to a "death threat" for patients infected with CRE, and it is urgent to explore new mechanisms of CRE resistance, which is closely related to the role of resistance genes, carbapenemases and efflux pumps. In addition, penicillin-binding protein, biofilms and iron carriers are expected to provide new research ideas to understand the drug resistance mechanism. The aim of this review is to summarize the mechanisms of CRE resistance and to provide new ideas for its treatment.

The clinical data and genetic characteristics of one child with mental retardation-56 (MRD56) diagnosed at the Department of Neonatology, Foshan Fosun Chancheng Hospital in October 2021 were retrospectively analyzed.The patient was admitted to the hospital with " 34 + 2 weeks of preterm birth, shortness of breath, and dyspnea for 0.5 hours". In the neonatal period, the patient had special facial features, hypotonia, weaning and feeding difficulties, laryngeal stridor.In infancy, the patient showed global psychomotor development delay, intellectual disability, epilepsy, etc.Magnetic resonance imaging of the brain showed delayed myelination and dysplasia of the cerebellum and corpus callosum.Whole-exome sequencing showed that the CLTC gene had a new missense mutation c.3334T>C (p.Trp1112Arg), and MRD56 was confirmed.A total of 32 cases of MRD56 were reported worldwide, with special facial features, intellectual disability, and psychomotor retardation as the main clinical manifestations.The cause is a mutation in the CLTC gene, which leads to abnormality in the structure of the clathrin encoded, thus affecting neurotransmitter transmission.This is the first report of MRD56 caused by the CLTC gene mutation in China, and a new clinical phenotype has been discovered.The finding enriches the phenotypic spectrum of the disease and provides a basis for clinicians to understand and study the disease.

The clinical data and genetic characteristics of one child with mental retardation-56 (MRD56) diagnosed at the Department of Neonatology, Foshan Fosun Chancheng Hospital in October 2021 were retrospectively analyzed.The patient was admitted to the hospital with " 34 + 2 weeks of preterm birth, shortness of breath, and dyspnea for 0.5 hours". In the neonatal period, the patient had special facial features, hypotonia, weaning and feeding difficulties, laryngeal stridor.In infancy, the patient showed global psychomotor development delay, intellectual disability, epilepsy, etc.Magnetic resonance imaging of the brain showed delayed myelination and dysplasia of the cerebellum and corpus callosum.Whole-exome sequencing showed that the CLTC gene had a new missense mutation c.3334T>C (p.Trp1112Arg), and MRD56 was confirmed.A total of 32 cases of MRD56 were reported worldwide, with special facial features, intellectual disability, and psychomotor retardation as the main clinical manifestations.The cause is a mutation in the CLTC gene, which leads to abnormality in the structure of the clathrin encoded, thus affecting neurotransmitter transmission.This is the first report of MRD56 caused by the CLTC gene mutation in China, and a new clinical phenotype has been discovered.The finding enriches the phenotypic spectrum of the disease and provides a basis for clinicians to understand and study the disease.

ObjectiveTo compare the effects of Taxillus chinensis from different hosts with different meridian affinity on bone microstructure and bone metabolism in ovariectomized osteoporotic rats， and investigate its mechanism of action. MethodEighty-eight specific-pathogen-free （SPF）-grade female Sprague-Dawley （SD） rats were selected and randomly divided into 11 groups： sham-operated group， model group， low-， medium- and high-dose groups of T. chinensis from Morus alba （2.5， 5， and 10 g·kg^-1）， low-， medium- and high-dose groups of T. chinensis from Cinnamomum cassia （2.5， 5， and 10 g·kg^-1）， and low-， medium- and high-dose groups of T. chinensis from C. burmannii （2.5， 5， and 10 g·kg^-1）. After 12 weeks of drug intervention， the rats were examined for proximal femur bone density and bone microstructure using dual-energy X-ray absorptiometry （DXA） and micro-computed tomography （Micro-CT）. Histopathological changes in rat femur were observed by the hematoxylin-eosin staining （HE）. Contents of serum estradiol （E₂）， bone Gla protein （BGP）， bone alkaline phosphatase （BALP）， tartrate-resistant acid phosphatase 5b （TRACP-5b） and pre-collagen type Ⅰ amino-terminal protopeptide （PINP） were measured by the enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to detect the messenger ribonucleic acid （mRNA） expressions of bone morphogenetic protein-2 （BMP-2）， Smad1， Smad9 and recombinant runt-related transcription factor 2 （Runx2） in rat humerus. Western blot was used to detect the protein expressions of BMP-2， p-Smad1/5/9 and Runx2 in rat humerus. ResultCompared with that in the sham-operated group， the femur microstructure of rats in the model group was significantly disrupted， with significant decreases in bone mineral density （BMD） value， bone volume fraction （BV/TV）， trabecular number （Tb.N）， and trabecular thickness （Tb.Th） （P<0.01）， and significant increases in trabecular separation （Tb.Sp） and structure model index （SMI） （P<0.01）. The serum levels of BGP， BALP， TRACP-5b and PINP were significantly increased （P<0.05， P<0.01）， and E₂ levels were significantly decreased （P<0.01）. The mRNA expressions of BMP-2， Smad1， Smad9， and Runx2 were significantly decreased in rat humerus （P<0.01）， and the protein expressions of BMP-2， p-Smad1/5/9， and Runx2 were significantly reduced （P<0.01）. Compared with the model group， the administration groups of T. chinensis from different hosts all elevated the BMD， BV/TV， Tb.N， Tb.Th， Tb.Sp， and SMI levels in the femur， improved bone microstructure， increased serum E₂ levels （P<0.05， P<0.01）， lowered the levels of serum BGP， BALP， TRACP-5b， and PINP， upregulated the mRNA expression of BMP-2， Smad1， and Runx2 and upregulated the mRNA expression levels of Smad9 （P<0.05， P<0.01）， and upregulated the protein expressions levels of BMP-2， p-Smad1/5/9， and Runx2 （P<0.01）. The best effect was observed in the group of T. chinensis from C. cassia. ConclusionT. chinensis from different hosts improved osteoporosis in ovariectomized rats， with the group of T. chinensis from C. cassia being the most potent among the administered groups， and its treatment of osteoporosis may regulate the balance of bone conversion by regulating BMP/Smad signaling pathway.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective:To summarize the clinical and genetic characteristics of Potocki-Shaffer syndrome (PSS).Methods:A retrospective study was conducted to analyze the clinical data of 1 patient diagnosed with PSS in the Department of Pediatrics of the Sixth Affiliated Hospital, Sun Yat-Sen University at February 2021.The data analyzed included clinical manifestations, biochemical tests and gene tests.Meanwhile, studies were retrieved from the China National Knowledge Internet database, Wanfang database, and PubMed database from the establishment of the database to December 2021 by taking " Potocki-Shaffer syndrome" " EXT2 gene" " AlX4 gene" and " PHF21A gene" as key words.Besides, genes were searched from the Online Frontal Analysis Mendelian Inheritance in Man.The clinical and genetic features of PSS patients were summarized. Results:The patient was 5 months and 21 days old, male, who was admitted to the hospital due to excessive growth in body mass for the past 3 months.The patient showed mental and motor retardation, overgrowth, concealed penis, hearing loss, and hypotonia.Whole exon sequencing of this patient revealed heterozygous deletions in the Chr11: 44069455-48188946 region, including the deletions of 3 autosomal dominant genes: EXT2, ALX4, and PHF21A.The patient was diagnosed with PSS.A total of 14 articles published in English were collected, involving this boy and other 35 patients.In these patients, 14 cases had point mutations, and 22 cases had large deletions. PHF21A gene variation was detected in 23 cases (dysgnosia in 22 cases, dyskinesia in 21 cases, language development delay in 18 cases). EXT2 gene variation was observed in 22 cases (exostoses in 13 cases). ALX4 gene variation was found in 19 cases (bilateral parietal foramina in 15 cases). Of 36 cases, 27 cases had craniofacial anomalies. Conclusions:The main clinical symptoms of PSS are language and motor developmental delay, intellectual disability, exostoses, bilateral parietal foramina, and craniofacial anomalies, which are closely related to 3 autosomal dominant genes ALX4, EXT2 and PHF21A.Genetic testing facilitates the clinical diagnosis of PSS, and the mutation types are dominated by point mutations and large deletions.

The animal models used in the experimental research of Traditional Chinese Medicine (TCM) to prevent and treat T2DM are mainly spontaneous and induced. The experimental research of TCM in the prevention and treatment of type 2 diabetes can be divided into Chinese medicine compound, Chinese medicine and its extract, Chinese medicine monomer. The mechanism is mainly through regulating intestinal flora, increasing insulin content, lowering blood sugar, lowering blood lipids, improving glucose tolerance, and improving gluconeogenesis, antioxidant, inhibit cell apoptosis, etc. play the role of preventing and treating T2DM in multiple links and multiple targets.

OBJECTIVE: To develop a model based on the clinical variables for evaluating the risk of distant metastasis in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: From September,2007 to June,2015,a total of 238 consecutive patients with biopsy-proven NPC in stage Ⅲ-Ⅳ(M0) based on the AJCC TNM staging manual were enrolled in this study,including 106 male and 34 female patients with a median age of 45 years (range 18-68 years).In this cohort,126 patients received concurrent chemoradiotherapy,and 24 received chemotherapy and radiotherapy,and 40 had induction chemotherapy.We used the least absolute shrinkage and selection operator (LASSO) method to select the most significant features for establishing the model for assessing the risks of distant metastasis. RESULTS: Among the 18 clinical variables tested,5 were significantly associated with distant metastasis in advanced NPC,including plasma Epstein-Barr virus (EBV) DNA,neutrophil/lymphocytes (NLR),VCA-IgA,concurrent chemoradiotherapy,and induction chemotherapy.Based on these 5 clinical variables,we established the following model:risk score=1.73×EBV DNA+0.54×NLR+0.38×VCA-IgA-0.95×concurrent chemoradiotherapy-2.37×induction chemotherapy+0.51.The cutoff point of this model was-0.62,which classified the patients into high-risk and low-risk groups for distant metastasis.This model showed a good performance in predicting distant metastasis in patients with advanced NPC (<0.01). CONCLUSIONS The model we established herein can be used for evaluating the risks of distant metastasis in patients with advanced NPC and provides assistance in the clinical decision-making on individualized treatment strategy.
Adult ; Aged ; Chemoradiotherapy ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Induction Chemotherapy ; Male ; Middle Aged ; Models, Statistical ; Multivariate Analysis ; Nasopharyngeal Carcinoma ; secondary ; therapy ; virology ; Nasopharyngeal Neoplasms ; pathology ; therapy ; virology ; Neoplasm Staging ; Prognosis ; Young Adult

Objective To research the efficacy and safety of sequential rivaroxaban use in reducing blood loss after applying tranexamic acid(TXA)in total hip arthroplasty(THA).Methods According to the design by the random control principle,150 pa tients undergoing unilateral primary THA from September 2012 to June 2015 were selected and randomly divided into the group A,B,C,D and E (n=30).The group A did not use TXA,the group B received intravenous drip of 10 mg/kg TXA at 10 min before skin incision,the group Creceived intravenous drip of 15 mg/kg TXA at 10 min before skin incision,the group D respectively received intravenous drip of 15mL/kg TXA at 10 min before skin incision and after 3 h,the group E received intravenous drip of 15 mL/kg TXA at 10 min before skin incision and articular cavity use of 1 g TXA before closing the incision.Oral 10 mg rivaroxaban was given at postoperative 6-12 h when the drainage volume was less than 30 mL/h and then the conventional dose was used until postoperative 35 d.The intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate,postoperative anticoagulation time,time of removing drainage tube,postoperative prothrombin time on postoperative 1 d,activated partial thromboplastin time,descend value of hemoglobin,and occurrence rates of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) were observed in the group A,B,C,D and E.Results The intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate and descend value of hemoglobin on postoperative 1 d had statistical differences among 5 groups(P＜0.05).The are significant differences between the group D and A in the intraoperative blood loss,postoperative drainage volume,hidden blood loss,blood transfusion rate,descend value of hemoglobin on postoperative 1 d,postoperative anticoagulation time and removal drainage tube time(P＜0.05).All cases had no symptomatic DVT and PE during the perioperative period and postoperative 3-month outpatient or telephone follow-up.Conclusion Sequential rivaroxaban use after applying TXA during THA perioperative period is safe and effective.Moreover intravenous drip of 15 mL/kg TXA at 10 min before skin incision and after 3 h has most significant effect in reducing bleeding volume during THA perioperative period.