Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective: To investigate the effects of poor sitting postures on muscle fatigue in schoolage children, so as to provide evidence for developing healthy sitting guidelines. Methods: In May 2024,30 children aged 6-12 were recruited from Changping District in Beijing. A combination of surface electromyography (sEMG) and psychophysical scales were used to assess muscle fatigue at varying deviation angles under four sitting postures (forward head tilt, lateral head tilt, uneven shoulder height, and forward trunk inclination). Oneway ANOVA and LSD post hoc multiple comparisons were employed to analyze the differences in electromyographic (EMG) data among various deviation angles under different sitting postures. Results: The mean integrated electromyography (IEMG) of representative muscles showed statistically significant differences (P<0.05) across deviation angles in all postures, with muscle fatigue worsening as deviation angles increased. Forward head tilt:significant IEMG differences were observed in the left/right sternocleidomastoid and left/right splenius capitis (F=13.74, 13.21, 5.43, 6.11,P<0.05). Lateral head tilt:significant differences were found in the right sternocleidomastoid muscle (SCM), right splenius capitis, and left trapezius (F=5.13, 4.73, 12.13, P<0.05). Uneven shoulder height:significant differences occurred in the right SCM, bilateral splenius capitis, and left trapezius (F=12.46, 12.56, 32.49, 5.98, P<0.05).Forward trunk inclination, significant differences were identified in the left/right SCM, left/right splenius capitis, and left/right lumbar muscles (F=4.45, 9.84, 14.49, 26.44, 8.02, 18.34, P<0.01). Temporal analysis revealed varying fatigue onset times across postures:severe fatigue occurred earlier in lateral head tilt and forward trunk inclination, while excessive forward head tilt, lateral head tilt, and uneven shoulder postures predominantly induced mild to moderate fatigue. Conclusions Under different sitting postures, both the integrated IEMG of relevant muscles and subjective evaluations in schoolaged children increase with greater postural deviattion. Head tilt and trunkleaning postures require particular intervention, with emphasis on unevenshoulder alignment and trunk inclination control.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Objective To investigate the relationship between serum miR-505,miR-15 and endoscopic activity of ulcerative colitis(UC).Methods 98 patients with UC from May 2020 to May 2022 were selected as the observation group,and 80 patients with irritable bowel syndrome(IBS)were selected as the control group during the same period.The modified Mayo score was used to evaluate the endoscopic activity in patients with UC,and the relationship among the changes of serum miR-505 and miR-15 levels and the endoscopic activity in patients with UC was analyzed.Results The level of serum miR-505 in observation group was lower than that in control group,while the level of miR-15 in observation group was higher than that in control group(P<0.05).The level of serum miR-505 in patients with active UC was lower than that in patients with the healing stage,while the level of serum miR-15 in patients with active UC was higher than that in patients with healing stage(P<0.05).The serum miR-505 level of E3 type was lower than that of E2 type and E1 type,and the serum miR-15 level of E3 type was higher than that of E2 type and E1 type(P<0.05).The Mayo score of type E3 was higher than that of type E2 and E1(P<0.05).Pearson correlation analysis showed that serum miR-505 was negatively correlated with Mayo score(r =-0.51,P<0.05),while serum miR-15 was positively correlated with Mayo score(r = 0.54,P<0.05).Receiver operator characteristic curve(ROC curve)results showed that the cut-off value of miR-505 was 0.93,and the area under the curve(AUC)for evaluating the endoscopic activity of patients with UC was 0.67(95%CI:0.659～0.785),and the sensitivity and specificity were 73.24%and 68.55%,respectively.The cut-off value of miR-15 was 0.85,and the AUC for evaluating the endoscopic activity of patients with UC was 0.69(95%CI:0.672～0.814),and the sensitivity and specificity were 76.38%and 69.72%,respectively.The AUC for the joint evaluation of UC by both was 0.82(95%CI:0.809～0.912),and the sensitivity and specificity were 84.56%and 68.49%,respectively.Conclusion Serum miR-505 levels decrease and serum miR-15 levels increase in UC patients than IBS,and the level is closely related to patients'pathological conditions and endoscopic activity.Combined detection of serum miR-505 and miR-15 has a good value in evaluating endoscopic activity in UC patients.

Objective: To investigate the mechanism of electroacupuncture (EA) for treating depression and to explore the role of brevican in the medial prefrontal cortex (mPFC) in modulating stress susceptibility and the antidepressant effects of EA in rats. Methods: Twenty-four Sprague–Dawley (SD) rats were equally divided into three groups: green fluorescent protein (GFP) + control, GFP + chronic unpredicted mild stress (CUMS), and short-hairpin RNA targeting on brevican (shBcan) + CUMS. Another 24 SD rats were equally divided into CUMS + GFP, CUMS + GFP + EA, and CUMS + shBcan + EA groups. Behavioral tests were conducted to assess depression-like behavior. Western blot analysis was used to evaluate the expression of brevican, aggrecan, GLuA1, and PSD95 in mPFC subregions. Results: Behavioral parameter evaluation show that rats in the shBcan + CUMS group exhibited a significantly reduced sucrose preference (P = .0002) and increased immobility time (P = .0011) compared to those in rats in the GFP + CUMS group. Western blotting showed that brevican expression was significantly downregulated in the PrL of the shBcan + CUMS group compared with that in the GFP + CUMS group (P = .0192). Furthermore, compared to the CUMS + GFP + EA group, the CUMS + shBcan + EA group exhibited a significantly decreased sucrose preference (P = .0334), increased immobility time (P = .0465), and increased latency to food (P = .0261). In the CUMS + shBcan + EA group, the EA-induced brevican and PSD95 overexpression was reversed, compared with that in the CUMS + GFP + EA group (P = .0454 and P = .0198, respectively). Conclusion EA exerts its antidepressant effects through the modulation of brevican expression in rats. Our findings highlight the important role for brevican in stress susceptibility, which could be a potential target for treating depression.

Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Objective To investigate the effects of glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) on glioma growth and macrophage infiltration. Methods Initially, the expression of GPIHBP1 in glioma samples and macrophage infiltration were analyzed using TCGA database, and these bioinformatics results were validated in clinical tissue samples. A stable glioma cell line overexpressing GPIHBP1 was then established to further explore the effects of GPIHBP1 overexpression on glioma cell proliferation, apoptosis, migration, and invasion. Finally, the impact of GPIHBP1 overexpression on tumor growth and macrophage infiltration was verified through xenograft experiments. Results TCGA database analysis revealed that GPIHBP1 expression was higher in low-grade gliomas compared to normal tissues, while it was lower in high-grade gliomas. Additionally, the expression level of GPIHBP1 in low-grade gliomas was higher than in high-grade gliomas, which was confirmed by immunohistochemistry (IHC). Western blot analysis confirmed the successful construction of the GPIHBP1-overexpressing glioma cell line. CCK-8, flow cytometry, scratch and Transwell assays demonstrated that the proliferation, migration and invasion capabilities of the stable cell line were reduced compared to the control group. Xenograft experiments further showed that the tumor growth and macrophage infiltration were decreased in the stable cell line. Conclusion The differential expression of GPIHBP1 in different grades of gliomas may be associated with tumor progression. Overexpression of GPIHBP1 can inhibit glioma growth, possibly by influencing the tumor microenvironment and promoting the polarization of macrophages towards the antitumor M1 phenotype, thereby inhibiting glioma growth.

High intensity focused ultrasound(HIFU)can non-invasively and safely focus sound waves on target region to ablate tumors.Using acoustic sensitizer combined with ultrasound to ablate tumors,Sonodynamic therapy(SDT)can ablate tumors at deep region with high precision.The progresses of HIFU combined with SDT for treating tumors were reviewed in this article.

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.

Adrenal vein sampling is required for the staging diagnosis of primary aldosteronism,and the frames in which the adrenal veins are presented are called key frames.Currently,the selection of key frames relies on the doctor's visual judgement which is time-consuming and laborious.This study proposes a key frame recognition algorithm based on deep learning.Firstly,wavelet denoising and multi-scale vessel-enhanced filtering are used to preserve the morphological features of the adrenal veins.Furthermore,by incorporating the self-attention mechanism,an improved recognition model called ResNet50-SA is obtained.Compared with commonly used transfer learning,the new model achieves 97.11%in accuracy,precision,recall,F1,and AUC,which is superior to other models and can help clinicians quickly identify key frames in adrenal veins.