[摘 要] 目的：探讨内吞作用相关基因FCHO2在各亚型乳腺癌中的表达及其与乳腺癌患者的预后和免疫细胞浸润的相关性。方法：应用免疫组化法和bc-GenExMiner v5.0数据库数据分析FCHO2在各亚型乳腺癌组织中的表达，通过GEO和TIMER数据库数据分析FCHO2与各亚型乳腺癌患者预后和免疫细胞浸润的关系，利用STRING和GEPIA数据库数据分析与FCHO2的互作蛋白网络和其与互作蛋白的相关性，通过UALCAN和DAVID数据库数据对乳腺癌组织中FCHO2表达相关基因进行KEGG和GO分析。结果：免疫组化法结果显示，FCHO2在管腔型和HER2+乳腺癌组织中均呈高表达（均P<0.05），且与HER2和Ki67表达有关联（P=0.03和P=0.007）。FCHO2高表达的管腔型乳腺癌患者总生存期（OS）和无复发生存期（RFS）均明显缩短（均P<0.05）。FCHO2蛋白与EPS15等多种蛋白表达相关且构成蛋白-蛋白互作网络。KEGG和GO分析显示，乳腺癌组织中FCHO2相关表达基因主要与昼夜节律、自噬等生物学过程有关，涉及叉头框蛋白O（FoxO）和TGF-β等信号通路。FCHO2表达与各亚型乳腺癌组织中的免疫细胞浸润相关（均P<0.05）。结论：FCHO2在管腔型、HER2+乳腺癌组织中呈高表达，且与管腔型乳腺癌患者预后及免疫细胞浸润相关，其可能成为乳腺癌治疗的潜在靶点。

[摘 要] 目的：探讨内吞作用相关基因FCHO2在各亚型乳腺癌中的表达及其与乳腺癌患者的预后和免疫细胞浸润的相关性。方法：应用免疫组化法和bc-GenExMiner v5.0数据库数据分析FCHO2在各亚型乳腺癌组织中的表达，通过GEO和TIMER数据库数据分析FCHO2与各亚型乳腺癌患者预后和免疫细胞浸润的关系，利用STRING和GEPIA数据库数据分析与FCHO2的互作蛋白网络和其与互作蛋白的相关性，通过UALCAN和DAVID数据库数据对乳腺癌组织中FCHO2表达相关基因进行KEGG和GO分析。结果：免疫组化法结果显示，FCHO2在管腔型和HER2+乳腺癌组织中均呈高表达（均P<0.05），且与HER2和Ki67表达有关联（P=0.03和P=0.007）。FCHO2高表达的管腔型乳腺癌患者总生存期（OS）和无复发生存期（RFS）均明显缩短（均P<0.05）。FCHO2蛋白与EPS15等多种蛋白表达相关且构成蛋白-蛋白互作网络。KEGG和GO分析显示，乳腺癌组织中FCHO2相关表达基因主要与昼夜节律、自噬等生物学过程有关，涉及叉头框蛋白O（FoxO）和TGF-β等信号通路。FCHO2表达与各亚型乳腺癌组织中的免疫细胞浸润相关（均P<0.05）。结论：FCHO2在管腔型、HER2+乳腺癌组织中呈高表达，且与管腔型乳腺癌患者预后及免疫细胞浸润相关，其可能成为乳腺癌治疗的潜在靶点。

Objective:To investigate the incidence rate and gene variation of methylmalonic academia (MMA) in Ji′nan city by analyzing biochemical and genetic screening results, and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods:The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6 800 newborns were tested for neonatal gene screening. MMAA, MMAB, MMACHC and MMUT genes in 4 800 cases were detected by high-throughput sequencing+ target area capture technology.Ultra-multiplex polymerase chain reaction+ target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2 000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed. Results:A total of 367 452 newborns were screened by tandem mass spectrometry, and 103 cases (56 males and 47 females) were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3 567.Among the 103 MMA cases, 76 were genetically diagnosed, and 4 gene variants of MMA ( MMAHC, MMUT, MMAA, MMADHC) were identified.A total of 6 800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA, with a total carrier rate of 4.68%.Specifically, the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6 800) and 1.43% (97/6 800), respectively. Conclusions:MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.

Objective:To establish the HPLC fingerprint of Centellae herba and determine the content of asiaticoside, madecassic acid and asiaticoside B simultaneously; To compare the quality differences of Centellae herba collected in different months. Methods:The chromatographic condition was a Shimadzu InertSustain C18 column (4.6 mm×250 mm, 5 μm) with a mobile phase consisting of acetonitrile and 2 mmol/L beta cyclodextrin in gradient elution at the flow rate of 0.8 ml/min. The detection wavelength was 204 nm, and the column temperature was 30 ℃. The different Centellae herba materials of collected in 2-12 months from Chenzhou were studied by the similarity evaluation combined with cluster analysis, principal component analysis and the three contents determination. Results:The HPLC fingerprint of Centellae herba was established and 9 common peaks were designated. The eleven samples were different, which can be aggregated into 4 categories and the quality of Centellae herba collected in July was the best. Conclusion:The established fingerprint and multi-components quantitative method are stable and reliable, which can provide a reference for the quality control and the utilization of Centellae herba resource.

Objective To investigate the screening strategy of group B streptococcus (GBS) in the reproductive tract of women in the third trimester and analyze its impact on pregnancy outcome. Methods A total of 85 461 pregnant women in 35-37 weeks of gestation from Bao′an Maternity and Child Health Hospital, Jinan University from January 2011 to June 2018 were enrolled. They were divided into 3 periods according to different GBS screening strategies, the unscreened period included 31 384 cases (36.72%), 33 267 cases (38.93%) were included in partial screening period, 20 810 cases (24.35%) were included in screening period. All GBS screening positive pregnant women were given intrapartum antibiotic prophylaxis (IAP). The impact on pregnancy outcomes, and the impact of different GBS collection transport and culture methods on the positive rate of GBS screening were analyzed. Results (1) The incidence of neonatal early onset GBS disease (EOGBSD) in unscreened period was 0.03% (11/31 773), in partial screening period was 0.02%(6/33 887), and in screening period, the incidence of neonatal EOGBSD decreased to 0, the difference was statistically significant (χ2=7.86, P=0.02).(2) The incidence of hematogenous infection of GBS in pregnant women was 0.02%(6/33 887) in partial screening period, and there was none in screening period, there was no significant difference (adjusted χ2=3.75, P=0.05). (3) In the screening period, the positive rate of GBS was 14.08%(2 719/19 306), which was significantly higher than the positive rate of GBS in the partial screening period (11.48%, 2 058/17 920; χ2=56.12, P=0.00). (4) Antibiotic sensitivity tests of 4 777 GBS strains showed that the antibiotics with higher resistance rate were tetracycline (81.52%, 3 896/4 777), erythromycin (66.59%, 3 181/4 777), and clindamycin (64.31%, 3 072/4 777). The combination of erythromycin, clindamycin and tetracycline was the most common resistant pattern, accounting for 48.80% (2 331/4 777). No penicillin, ceftriaxone or vancomycin resistant strains was found. Conclusions GBS screening strategy in different regions could combine the local neonatal EOGBSD incidence rate, maternal GBS colonization rate, and the socioeconomic factors to determine whether universal GBS screening or screening for high-risk maternal women. GBS screening positive rate is related to the population, scope of the investigation, the sample collection, delivery and culture methods. The multi-drug resistance rate of GBS is high.[Key words] Streptococcus agalactiae; Streptococcal infections; Neonatal sepsis; Prenatal diagnosis; Pregnancy trimester, third; Pregnancy outcome

OBJECTIVE:To observe clinical efficacy and safety of compound α-ketoacid tablet in the treatment of type 2 dia-letic mellitusc(T2DM)complicated with early diabetic nephropathy. METHODS:A total of 180 T2DM patients with early nephrop-athy during Jan. 2013-Dec. 2015 selected as research objects were divided into group A,B,C according to random number table, with 60 cases in each group. Group C was given basic symptomatic treatment. Group A was additionally given Compound α-ketoac-id tablets 2.52 g orally,tid,on the basis of group C. Group B was additionally given Compound α-ketoacid tablets 5.04 g orally, tid,on the basis of group C. Three groups were treated for consecutive 24 weeks. The renal function indexes (BUN,Cr,GFR, urine ALB),blood glucose indexes (FPG,PPG,HbA1c),blood pressure indexes (SBP,DBP) and nutritional indexes (serum ALB,PA,Hb) were observed in 3 groups before and after treatment. The occurrence of ADR was recorded in 3 groups. RE-SULTS:Before treatment,there was no statistical significance in renal function indexes,blood glucose indexes,blood pressure in-dexes or nutritional indexes among 3 groups(P>0.05). After treatment,urine levels of ALB,HbA1c and SBP were decreased sig-nificantly in 3 groups;the group B was significantly lower than the group A;the group A was significantly lower than the group C. The levels of serum ALB,PA and Hb were decreased significantly in group A and C;the group B was significantly higher than the group A;the group A was significantly higher than group C,with statistical significance (P<0.05). The incidence of ADR in 3 groups were 8.3％,10.0％ and 6.7％ respectively,without statistical significance(P>0.05). CONCLUSIONS:Compound α-keto-acid tablet can significantly improve renal function,control blood glucose and blood pressure levels and complete necessary nutri-ents in T2DM patients with early nephropathy patients with good safety. High dose are more effective.

Objective To study the relationship between cardiovascular diseases (CVD) and ischemia modified albumin (IMA) in patients with type 2 diabetes mellitus (T2DM).Methods Ninety-six patients with T2DM were selected as T2DM group retrospectively,and 60 cases of healthy physical examination were selected as control group,the patient' s medical history data were collected,the IMA was detected and Doppler ultrasound examination was performed.The relationship between serum IMA level and some laboratory parameters were analyzed.Results Twenty-eight cases (29.2％,28/96) occurred CVD among 96 cases of T2DM patients.The level of IMA in T2DM group was higher than that in control group [(58.25 ± 11.84) kU/L vs.(23.38 ± 6.41) kU/L],there was significant difference (P ＜ 0.05).The levels of IMA in T2DM combined with CVD group (28 cases) and T2DM not combined with CVD group (68 cases) were(91.46 ± 13.63),(47.91 ± 9.38) kU/L; the level of IMA in T2DM combined with CVD group was higher than that in T2DM not combined with CVD group and control group,there was significant difference (P ＜ 0.05).All patients completed echocardiography,Spearman correlation analysis between IMA and echocardiography indicators showed that the level of IMA was positively correlated with left ventricular end-diastolic diameter (r =0.546,P =0.031),interventricular septal thickness (r =0.427,P =0.039),posterior wall diameter of left ventricle at end-diastolic (r =0.582,P =0.026) and left venifieular mass index (r =0.339,P =0.042),and IMA was negatively correlated with ejection fraction of left ventricle (r =-0.561,P =0.024).Multivariable Logistic regression analysis showed that IMA,high-sensitivity C reactive protein,diabetes duration,fasting blood glucose levels were independent risk factors for CVD.Conclusions Serum IMA level is significantly higher in T2DM patients.IMA level is a related risk factor for CVD.

Objective To investigate the correlation between homocysteine(Hcy) and atheroscIerosis (AS) in type 2 diabetic patients.Methods A total of 98 type 2 diabetic patients in Donghua Hospital Affiliated to Sun Yet-Sen University were enrolled in this study and served as diabetic group.Meanwhile diabetic patients were divided into aged group(aged ＞65 years old) and young and middle aged group(＜65 years old).Fortynine healthy volunteers were used as control group.Intima-media thickness(IMT) and atherosclerotic plaqlles of the extracranial common carotid artery were detected by high-resolution B-mode ultrasoograph.Fasting plasma glucose (FPG),postprandial 2 h glucose (2 hPG),glycosylated hemoglobin (HbA1 c),total cholesterol (TC),total triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),creactive protein(CRP) and Hcy were measured.Correlation analysis of Hcy and IMT with other parameters was performed.Results Hcy level in patients with type 2 diabetes were (34.15 ± 10.25) μmol/L,significantly higher than those in healthy control group((8.46 ± 3.62) μmol/L,P =0.014).Hcy level in age group((40.63 ± 11.78) μmol/L) was significantly higher than that of young and middle aged group((26.54 ±9.38) μmol/L,P =0.028).IMT value and plaque detection rate in elderly patients were (1.28 ±0.26) mm and 66.1％ (20/41),significantly higher than that in the young and middle aged group((1.02 ±0.20) mm and 38.9％,P =0.041,0.027).Multiple stepwise regression analysis showed that age (OR =1.46,95％ CI:1.18-6.36,P =0.029),duration of diabetes (OR =2.62,95％ CI:1.78-7.43,P ＜ 0.001),LDL-C (OR =1.54,95％CI 1.19-6.27,P =0.028),CRP(OR =1.38,95％ CI 1.11-4.84,P =0.032),Hcy(OR =2.45,95％ CI 1.34-6.61,P =0.018)) were independent risk factors for carotid AS.Conclusion The Hcy level significantly increase in type 2 diabetic patients.Hcy,age,duration of diabetes,LDL-C,CRP are independently risk factors of neck AS.

Objective To explore the risk factors of Pseudomonas aeruginosa infection in diabetic foot .Methods 136 patients with diabetic foot were divided into infection group (n=12) and control group(n=124) according to whether Pseudomonas aerugi-nosa infection existed .Their age ,gender ,body mass index (BMI) and complications were recorded ,and their hemoglobin ,fasting plasma glucose (FPG ) ,two hours postprandial blood glucose (2hPBG ) ,glycosylated hemoglobin A1c (GHbA1c) ,cholesterol , triglycerides ,low density lipid(LDL) ,high density lipid(HDL) ,serum albumin(SALB) were detected .Logistic regression analysis was employed to analyze the risk factors of Pseudomonas aeruginosa infection .Results Incidence of Pseudomonas aeruginosa infec-tion in diabetic foot was 8 .8% .Among them ,the infection incidences of elderly patients and patients with diabetic nephropathy were 11 .6% and 12 .7% ,respectively .Univariate analysis showed that male ,advanced age ,BMI ,duration of diabetes ,history of heart disease ,diabetic nephropathy ,FPG ,2hPBG ,GHbA1c ,low hemoglobin and low SALB were associated risk factors of Pseudomonas aeruginosa infection(P<0 .05) .After correction of confounding factors such as male ,BMI ,history of heart disease ,2hPBG and low hemoglobin ,advanced age ,duration of diabetes ,diabetic nephropathy ,GHbA1c and low SALB were independent risk factors for Pseudomonas aeruginosa infection(P<0 .05) .Conclusion Advanced age ,duration of diabetes ,diabetic nephropathy ,GHbA1c and low SALB are independent risk factors for Pseudomonas aeruginosa infection .

Objective To determine the levels of vitamin D in the peripheral blood of patients with systemic lupus erythematosus(SLE).Methods Seventy-eight cases of SLE were selected as SLE group,42 cases of chronic nephritis (CN) were as CN group,and 40 cases of healthy persons were as control group.Vitamin D levels were detected by enzyme-linked immunosorbant assay.The correlation of vitamin D levels in patients with SLE and 24 h urinary protein excretion,SLE disease activity (SLEDAI) score,anti-ds-DNA antibodies,complement C3 were analyzed,and the relationships between vitamin D levels and kidney damage were estimated.Results The vitamin D levels in SLE group were (13.3 ± 6.2) μ g/L,significantly lower than those in CN group [(21.4 ± 9.7) μ g/L] and control group [(20.8 ± 9.5) μ g/L] (P ＜ 0.05),and the difference was not statistically significant between CN group and control group (P ＞ 0.05).The vitamin D levels in SLE and lupus nephritis (LN) patients were significantly lower than those in SLE and non-LN patients [(9.8 ±6.1) μg/L vs.(15.9 ±7.8) μg/L,P ＜0.05].Vitamin D levels in SLE patients were negatively correlated with SLEDAI score,anti-ds-DNA antibodies and 24 h urinary protein excretion (r =-0.712,-0.682,-0.769,P ＜ 0.05),and were positively correlated with complement C3(r =0.608,P ＜ 0.05).Conclusions The vitamin D levels in SLE patients decrease significantly and have close relationship with disease activity.It can not only reflect disease activity,but also act as a useful marker to predict visceral involvement.