Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Objective To evaluate the efficacy of human papillomavirus E6/E7(HPV E6/E7)mRNA combined with colposcopy in screening cervical cancer and precancerous lesions.Methods A total of 480 patients with suspected cervical precancerous lesions in the hospital from July 2022 to De-cember 2024 were retrospectively selected as research objects.All the patients underwent HPV E6/E7 mRNA testing,colposcopy,and pathological examination.Taking the pathological examination results as the diagnostic golden standard,the diagnostic values of HPV E6/E7 mRNA and colposcopy alone as well as their combination were analyzed.Results The pathological examination results of 480 pa-tients showed that there were 192 negative cases,including 1 case of normal cervix and 191 cases of benign lesions;there were 288 positive cases,including 133 cases of low-grade squamous intraepithe-lial lesions(LSIL),110 cases of high-grade squamousintraepithelial lesions(HSIL),and 45 cases of cervical squamous cell carcinoma(SCC).The colposcopy results showed 211 true-positive cases and 138 true-negative cases;the HPV E6/E7 mRNA test results showed 199 true-positive cases and 137 true-negative cases;the combined test results showed 239 true-positive cases and 174 true-negative cases.The sensitivity(95.22％),specificity(75.98％),accuracy(86.04％),positive predic-tive value(81.29％),and negative predictive value(93.55％)of the combined test were signifi-cantly higher than those of each individual test(P＜0.001).Moreover,the consistency between the combined test and pathological results(Kappa=0.718,P＜0.001)was also significantly high-er than that of each individual test.Conclusion Compared with HPV E6/E7 mRNA or colposcopy alone,the combined test has higher clinical application value in screening of cervical precancerous lesions and cervical cancer,shows stronger consistency with pathological results,and is of great sig-nificance for the early differential diagnosis of cervical precancerous lesions and cervical cancer.

Objective To explore the regulatory mechanism of NFE2L2/KEAP1 in alveolar bone repair induced by periodontitis.Methods A rat periodontitis model was established and divided into four groups:Control group(n=6);Periodontitis model group(n=6);Periodontitis+lentivirus empty vector group(n=6);Periodontitis+NFE2L2 overexpression plasmid group(n=6).Histopathological changes in each group were observed using HE staining.TRAP staining was used to detect osteoclast positivity,while ELISA was employed to measure inflammatory cytokine levels in tissues.Immunofluorescence and qPCR were used to detect NFE2L2 expression,and western blot was used to assess the expression of osteogenic proteins ALPL2,RUNX2,and COL1.Primary periodontal ligament cells(hPDLCs)were cultured,and cells were transfected to overexpress NFE2L2 and KEAP1.The cells were divided into six groups:Normal group;Model group;pcDNA-NC group;pcDNA-NFE2L2 group;pc-NFE2L2+pcDNA-NC group;pc-NFE2L2+pcDNA-KEAP1 group.A cellular model was established,and the morphology of primary hPDLCs was observed under a microscope.Cell proliferation was assessed using CCK-8.Osteogenic mineralization was observed using alizarin red staining,and western blot was used to detect osteogenic proteins and autophagy markers.Cell migration was observed using a scratch assay.Results(1)After model induction,redness,swelling of the gums,extensive inflammatory infiltration,and alveolar bone resorption were observed,confirming successful model establishment.Partial tissue recovery occurred after NFE2L2 overexpression via lentivirus.(2)After model induction,osteoclast positivity increased,confirming successful model establishment.Overexpression of NFE2L2 reduced osteoclast positivity(P<0.001).(3)After model induction,levels of IL-1β,IL-10,and TNF-α were significantly higher than in the normal group(P<0.05),confirming successful model establishment.Transfection with NFE2L2 lentivirus reduced inflammatory cytokine levels(P<0.0001).After model induction,osteogenic protein expression decreased compared to the normal group,but overexpression of NFE2L2 increased osteogenic protein expression(P<0.05).(5)LPS treatment significantly reduced cell viability,while NFE2L2 overexpression enhanced it(P<0.0001).(6)LPS treatment reduced calcified nodules,while NFE2L2 overexpression increased them.Addition of pcDNA-KEAP1 reduced mineralized nodules.(7)LPS treatment decreased osteogenic protein expression,while NFE2L2 overexpression increased it.However,addition of pcDNA-KEAP1 reduced osteogenic protein expression(P<0.05).(8)LPS treatment reduced cell migration,whereas NFE2L2 overexpression enhanced it(P<0.0001).(9)Expression of autophagy markers decreased after LPS treatment,but increased after transfection with NFE2L2 plasmid.However,addition of pcDNA-KEAP1 reduced the expression of autophagy markers(P<0.05).Conclusion This study identified the regulatory role of NFE2L2/KEAP1 in periodontitis,providing a scientific basis for the treatment of periodontitis.

Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95％CI 0.97-0.99,P＜0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P＜0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P＞0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95％confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95％CI-0.92～-0.20,P=0.000),higher EDV levels(SMD 0.47,95％CI 0.12～0.83,P=0.028)and higher PR levels(SMD0.96,95％CI 0.13～1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.