Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To investigate the relationship between the virulence and the carbapenem resistance phenotype of Klebsiella pneumoniae from blood infection,and to identify carbapenem-resistant and hypervirulent Klebsiella pneumoniae(CR-HVKP)strains.Methods:A total of 192 Klebsiella pneumoniae strains were isolated from blood culture of patients with bloodstream infections from 2016 to 2019,of which 96 isolates were carbapenem-resistant Klebsiella pneumoniae(CRKP)and 96 were carbapenem-sensitive Klebsiella pneumoniae(CSKP).The drug susceptibility was detected by VITEK-2 automatic microbial analyzer;carbapenemase genes,virulence genes and capsule typing were detected by polymerase chain reaction;the high viscosity phenotype of strains was detected by string test,and the genome characteristics of CR-HVKP were detected by whole genome sequencing.Serum killing and biofilm formation test were used to further verify the virulence of CR-HVKP.Results:There were significant differences in drug resistance to common antibiotics,except for minocycline between CSKP and CRKP isolates(all P<0.05).92 out of 96 CRKP isolates carried carbapenemase genes,mainly blaKPC-2.The string tests were positive in 4 isolates of CRKP and 36 isolates of CSKP(P<0.05).The detection rates of virulence genes Kfu,aerobictin,iutA,ybtS,rmpA,magA,allS,and capsule antigen K1 and K2 in CSKP group were significantly higher than those in CRKP group(all P<0.05).One HVKP strain was detected in the CRKP group(CR-HVKP)and 36 HVKP was detected in the CSKP group(P<0.05).The CR-HVKP strain belonged to the MLST412,serotype K57,expressed iutA,entB,mrkD,fimH,and rmpA virulence genes,and showed strong biofilm formation and significantly increased serum resistance.Whole genome sequencing results showed that this CR-HVKP isolate carried blaSHV-145,blaTEM-1,blaCTX-M-3,fosA6,oqxA5,oqxB26,and aac(3)-Ⅱd resistance genes,accompanied by abnormalities in outer membrane protein K(OmpK)35 and OmpK36.Conclusions:The drug resistance of CRKP is significantly higher than that of CSKP,while CRKP carrying fewer virulence genes in both number and types compared to CSKP.A new MLST type of carbapenem-resistant and hypervirulent Klebsiella pneumoniae strain has been detected,which requires clinical awareness and epidemiological monitoring.

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.
Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Objective:To investigate the efficacy of the classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine.Methods:A retrospective case series study was made on 105 patients with single segment facet joint dislocation in subaxial cervical spine admitted to Zhengzhou Orthopedic Hospital from January 2015 to October 2022. There were 63 males and 42 females, with the age range of 22-78 years [(47.5±3.6)years]. Preoperative American Spinal Cord Injury Association (ASIA) classification was grade A in 23 patients, grade B in 45, grade C in 22, grade D in 15 and grade E in 0. The classification of surgical approach was based on the presence or not of continuity between anterior and posterior subaxial cervical structures and the movability of the posterior cervical facet joint on CT two-dimensional images, including anterior cervical surgery if both were presented and posterior facet joint resection plus anterior cervical surgery if there was discontinuity between anterior and posterior subaxial cervical structures or posterior facet joint fusion. Reduction procedures were applied in accordance with the type of facet joint dislocation classified based on the position of the lower upper corner of facet joint, including skull traction or manipulative reduction for the dislocation locating at the dorsal side (type A), intraoperative skull traction and leverage technique for the dislocation locating at the top (type B) and intraoperative skull traction and leverage technique with boosting for the dislocation locating at the ventral side (type C). If the dislocation of two facet joints in the same patient was different, the priority of management followed the order of type C, type B and type A. The reduction success rate, operation time and intraoperative blood loss were recorded. The cervical physiological curvature was evaluated by comparing the intervertebral space height and Cobb angle before operation, at 3 months after operation and at the last follow-up. The fusion rate of intervertebral bone grafting was evaluated by Lenke grading at 3 months after operation. The spinal cord nerve injury was assessed with ASIA classification before operation and at 3 months after operation. Japanese Orthopedic Association (JOA) score was applied to measure the degree of cervical spinal cord dysfunction before operation and at 3 months after operation, and the final follow-up score was used to calculate the rate of spinal cord functional recovery. The occurrence of complications was observed.Results:All patients were followed up for 3-9 months [(6.0±2.5)months]. The reduction success rate was 100%. The operation time was 40-95 minutes [(58.6±9.3)minutes]. The intraoperative blood loss was 40 to 120 ml [(55.7±6.8)ml]. The intervertebral space height was (4.7±0.3)mm and (4.7±0.2)mm at 3 months after operation and at the last follow-up, significantly decreased from preoperative (3.1±0.5)mm (all P<0.01), but there was no significant difference in intervertebral space height at 3 months after operation and at the last follow-up ( P>0.05). The Cobb angle was (6.5±1.3)° and (6.3±1.2)° at 3 months after operation and at the last follow-up, significantly increased from preoperative (-5.4±2.2)° (all P<0.01), but there was no significant difference in Cobb angle at 3 months after operation and at the last follow-up ( P>0.05). The fusion rate of intervertebral bone grafting evaluated by Lenke grading was 100% at 3 months after operation. The ASIA grading was grade A in 15 patients, grade B in 42, grade C in 29, grade D in 12 and grade E in 7 at 3 months after operation. The patients showed varying degrees of improvement in postoperative ASIA grade except that 15 patients with preoperative ASIA grade A had partial recovery of limb sensation but no improvement in ASIA grade. The JOA score was (13.3±0.6)points and (13.1±0.6)points at 3 months after operation and at the last follow-up, significantly improved from preoperative (6.8±1.4)points (all P<0.01), but there was no significant difference in JOA score at 3 months after operation and at the last follow-up ( P>0.05). The rate of spinal cord functional recovery was (66.3±2.5)% at the last follow-up. All patients had no complications such as increased nerve damage or vascular damage. Conclusion:The classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine has advantages of reduced facet joint dislocation, recovered intervertebral space height and physiological curvature, good intervertebral fusion and improved spinal cord function.

Objective:To compare the clinical efficacies of precision targeted and traditional percutaneous vertebroplasty (PVP) in the treatment of refracture of injured vertebra after operation for Kümmell disease.Methods:A retrospective cohort study was conducted to analyze the clinical data of 23 Kümmell disease patients suffering from refracture of injured vertebra after PVP in Zhengzhou Orthopedic Hospital from October 2014 to October 2018. The patients included 7 males and 16 females, aged 53-89 years [(69.3±3.5)years]. There were 11 patients of stage I Kümmell disease and 12 patients of stage II Kümmell disease. The vertebral distribution of fracture was T 11 (3 patients), T 12 (9 patients), L 1 (8 patients) and L 2 (3 patients). Eleven patients received traditional PVP treatment (traditional PVP group) and 12 patients received precision targeted PVP treatment (targeted PVP group). The operation time, amount of bone cement injection and filling of bone cement in the fracture space were compared between the two groups. The visual analogue score (VAS) and Oswestry disability index (ODI) were also compared before operation, at 2 days, 1 month, 3 months, 6 months after operation, and at the last follow-up. The rates of bone cement leakage and re-collapse of injured vertebra were observed in the two groups. Results:The patients were followed up for 12-36 months [(24.2±2.6)months]. There were no significant differences in the operation time or amount of bone cement injection between the two groups (all P>0.05). All the fracture spaces in the targeted PVP group were fully filled with bone cement, while 4 patients in the traditional PVP group showed inadequate filling of the fracture area ( P<0.05). The VAS values in the targeted PVP group were (8.9±0.5)points, (1.6±0.2)points, (1.7±0.1)points, (1.8±0.1)points, (1.9±0.3)points, and (1.8±0.4)points before operation, at 2 days, 1 month, 3 months, 6 months after operation and at the last follow-up; and those in the traditional PVP group were (9.1±0.9)points, (1.8±0.4)points, (1.8±0.2)points, (2.0±0.4)points, (2.1±0.2)points, and (2.4±0.3)points, respectively. The VAS values of both groups were significantly decreased at 2 days, 1 month, 3 months, 6 months after operation, and at the last follow-up compared with those before operation (all P<0.05), but there was no significant difference between different time points after operation (all P>0.05). No significant differences were found in the VAS values between the two groups before operation and at 2 days, 1 month, 3 months and 6 months after operation (all P>0.05). However, the VAS value in the targeted PVP group was significantly lower than that in the traditional PVP group at the last follow-up ( P<0.05). The ODI values in the targeted PVP group were 38.5±4.3, 7.2±2.3, 7.3±2.0, 7.2±1.8, 7.3±2.4, and 7.4±2.5 before operation and at 2 days, 1 month, 3 months, 6 months after operation, and at last follow-up; and those in the traditional PVP group were 37.8±4.1, 7.5±2.5, 7.7±1.9, 7.9±2.4, 8.1±2.6, and 9.6±2.4, respectively. The ODI values of both groups were significantly decreased at 2 days, 1 month, 3 months, 6 months after operation and at the last follow-up compared with those before operation (all P<0.05), but there were no significant differences between different time points after operation (all P>0.05). The ODI values were not significantly different between the two groups before operation and at 2 days, 1 month, 3 months, 6 months after operation (all P>0.05), but the ODI value in the targeted PVP group was significantly lower than that in the traditional PVP group at the last follow-up ( P<0.05). There were no significant differences in the rates of bone cement leakage or re-collapse of injured vertebra between the two groups (all P>0.05). Conclusion:Compared with traditional PVP treatment for refracture of injured vertebra after operation for Kümmell disease, targeted PVP can make bone cement injection fully dispersed, greatly reduce pain and promote functional recovery.

OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G₁ phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION TPA induces NB4 cell cycle arrest in G₁ phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Humans ; Leukemia, Promyelocytic, Acute ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Cell Division ; Apoptosis ; RNA, Messenger ; Cell Proliferation

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.
Child ; Child, Preschool ; Graft vs Host Disease/complications* ; Hematopoietic Stem Cell Transplantation ; Humans ; Quality of Life ; Retrospective Studies ; Thalassemia/therapy* ; beta-Thalassemia/therapy*

Abstract: Objective　To understand the distribution and drug resistance of common pathogens of fungal bloodstream infection in Sichuan, and to provide reference for clinicians to empirically treat fungal bloodstream infection. Methods　From November 1, 2019 to December 31, 2020, fungal strains isolated from blood culture of patients diagnosed with bloodstream infection in 19 tertiary first-class general hospitals in Sichuan Province were collected for mass spectrometry identification and drug susceptibility, and the results were statistically analyzed, along with a retrospective analysis of clinical data. Results　A total of 255 fungal strains were received and identified by mass spectrometry, 215 strains of Candida spp (84.3%), 28 strains of Cryptococcus neoformans (11.0%), 4 strains of Talaromyces marneffei (1.6%) and 8 strains of others (3.1%). Among the Candida spp 90 strains of Candida albicans, 39 strains of Candida parapsilosis complex, 36 strains of Candida glabrata, 33 strains of Candida tropicalis, 8 strains of Candida guilliermondii, and 9 strains of other Candida. In the department, the ICU was predominant, accounting for 35.7%. The top four Candida (Candida albicans, Candida parapsilosis complex, Candida glabrata, Candida tropicalis) were analyzed for drug sensitivity, Candida albicans and Candida parapsilosis complex group were more sensitive to antifungal drugs, the sensitivity rates of Candida albicans to fluconazole, voriconazole, anidulafungin, caspofungin, micarafungin were 89.2%, 92.8%, 97.6%, 97.6%, 96.4%, respectively. The sensitivity rates of Candida parapsilosis to fluconazole and voriconazole were 89.7% and 94.9%, and to anidulafungin, caspofungin and micafungin were all 100%. Echinocandins had stronger antibacterial activity against Candida spp., Candida parapsilosis complex and Candida tropicalis had 100% sensitivity to echinocandins, Candida albicans had more than 95% sensitivity to echinocandins, and Candida glabrata had about 90% sensitivity to echinocandins. Candida tropicalis was less sensitive to fluconazole and voriconazole with 66.7% and 54.5%, and the sensitivity of Candida glabrata to fluconazole was mainly concentrated in susceptible dose dependent (SDD), accounting for 91.4%. The four Candida species did not show resistance to amphotericin B, all of them showed wild-type strains, Candida tropicalis showed the highest non-wild-type rate to posaconazole and itraconazole with 21.2% and 36.4%, and the drug sensitivity results of Cryptococcus neoformans showed that 4 out of 23 strains showed resistance to amphotericin B (non-wild-type) and 3 strains showed resistance to fluconazole (non-wild-type). Conclusions　The fungus of bloodstream infection is mainly Candida spp.. Among of them, Candida albicans accounts for the highest percentage, echinocandins have good antibacterial effect on Candida, Candida is sensitive to amphotericin B as wild type, but Candida tropicalis has slightly higher resistance rate to fluconazole and voriconazole, and the non-wild type rate of Cryptococcus neoformans to amphotericin B is increasing, and clinicians should pay high attention to the rational use of antifungal drugs.