[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

[The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients].

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

[Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell].

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 µmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 µmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 µmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 µmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

[Nutritional status predicts clinical outcomes in patients with gastric cancer undergoing radical gastrectomy].

Objective: To evaluate the effect of nutritional status on clinical and pathological data for stage Ⅰ-Ⅳ gastric cancer patients from the cancer survival investigation information. Methods: A database of 302 consecutive gastric cancer patients underwent radical gastrectomy was enrolled in this study. The clinical and pathological information of them were corrected and the relationship between the nutritional index and the patients survival time were analyzed by a Cox regression model. Results: The clinical data analysis of 302 patients with gastric cancer who received total gastric resection indicated that the nutritional status was related to the stage of tumor patients, suggesting that the later the stage was, the more necessary the nutritional therapy intervention was. Univariate analysis showed that Ⅲ+Ⅳ of TNM staging (HR=4.417, 95%CI:2.483-6.351; P =0.029), patient age of 65 and above (HR=2.217, 95%CI:0.522-3.912; P =0.038), lymph node metastasis positive (HR=2.517, 95%CI:0.516-4.518; P=0.036), poor tumor differentiation (HR=3.626, 95%CI:0.721-6.531; P =0.021) and low PNI (HR=2.612, 95%CI: 0.712-4.512; P =0.029) is an important risk factor for poor prognosis. In the multivariate analysis, Ⅲ+Ⅳ of TNM staging (HR=3.821, 95%CI:1.923-5.719; P =0.014), patient age of 65 and above (HR=1.168, 95%CI:0.321-2.015; P =0.036) and low PNI (HR=2.435, 95%CI:1.024-3.846; P =0.039) was independently correlated with poor survival time; When age was used as a stratification factor, the correlation between CONUT recurrence and survival in patients with gastric cancer ≥65 years old after total gastric resection was analyzed and compared. For disease-free survival, the CONUT high group (>3) was 25.2 months, while the CONUT low group (≤3) was 30.9 months, (χ2=3.763,P=0.029), showing a significant difference. For the overall survival, the CONUT high(>3) group was 30.3 months, compared with the CONUT low(≤3) group at 34.5 months, (χ2=4.924,P=0.042), and the difference was also statistically significant. Conclusions: High controlling nutritional status is an independent risk factor associated with poor gastric cancer survival and it is an independent risk factor in predicting overall survival (OS) in elderly (≥65) gastric cancer after radical gastrectomy.

[A nomogram to predict non-sentinel lymph node metastasis for breast cancer patients with positive axillary sentinel lymph node].

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P<0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P<0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

Linear polarization grating combining a circular polarization grating with a special cycloidal diffractive quarter waveplate.

We introduce and demonstrate a switchable novel linear polarization grating (LPG) consisting of a circular polarization grating (CPG) and a special cycloidal diffractive quarter waveplate (CQWP). The CQWP is developed that marvelously matches the polarization-state of beams passing through the CPG. Such an LPG is so polarization-sensitive that it can split an incident linear polarized beam into two proportionally controllable left- or right-handed circularly polarized lights. We establish rigorous simulation model based on finite element method to investigate near-field polarization-state distribution of CPGs. Furthermore, LPGs are demonstrated and the diffraction properties are obtained with simulation and Jones Matrix analysis. The combination of CPGs and CQWPs is achieved with polymerizable liquid crystal. The experimental results of deflection angle and polarization selectivity of LPGs are consistent with those of simulation.

Correction to: Strengthening Surgery Strengthens Health Systems: A New Paradigm and Potential Pathway for Horizontal Development in Low- and Middle-Income Countries.

In the original article, Ziad C. Sifri's first and last names were interchanged. It is correct as reflected here.

Strengthening Surgery Strengthens Health Systems: A New Paradigm and Potential Pathway for Horizontal Development in Low- and Middle-Income Countries.

Global health is transitioning toward a focus on building strong and sustainable health systems in developing countries; however, resources, funding, and agendas continue to concentrate on "vertical" (disease-based) improvements in care. Surgical care in low- and middle-income countries (LMICs) requires the development of health systems infrastructure and can be considered an indicator of overall system readiness. Improving surgical care provides a scalable gateway to strengthen health systems in multiple domains. In this position paper by the Society of University Surgeons' Committee on Global Academic Surgery, we propose that health systems development appropriately falls within the purview of the academic surgeon. Partnerships between academic surgical institutions and societies from high-income and resource-constrained settings are needed to strengthen advocacy and funding efforts and support development of training and research in LMICs.

[Sorafenib combined with chemotherapy and donor lymphocyte infusion as salvage therapy in patients with FLT3-positive acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation].

To explore the efficacy of sorafenib combined with chemotherapy and donor lymphocyte infusion (DLI) in patients with FLT3-positive acute myeloid leukemia (AML) relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of the 14 patients relapsed after allo-HSCT, 9 achieved complete remission after salvage therapy of sorafenib combined with chemotherapy and DLI, 6 with complete molecular remission, 2 with partial remission, and 3 with no response. With a median follow up of 220 (range, 30-1 782) days after post-transplantation relapse, 7 patients were still alive and 7 died. Salvage therapy of sorafenib combined with chemotherapy and DLI shows a decent therapeutic effect for FLT3-positive AML relapsed after allo-HSCT.