Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Purpose: This study aimed to investigate the molecular characteristics associated with better prognosis in breast cancer. Methods: We performed targeted sequencing of 962 genes in 56 samples, categorizing them into long-term and short-term survival groups as well as chemotherapy-sensitive and chemotherapy-resistant groups for further analyses. Results: The results indicated that the tumor mutational burden values were significantly higher in the short-term survival and chemotherapy-resistant groups (p = 0.008 and p = 0.003, respectively). Somatic mutation analysis revealed that the mutation frequencies of BCL9L and WHSC1 were significantly lower in the long-term survival group than those in the short-term survival group (p = 0.029 and p = 0.024, respectively). CREB-regulated transcription coactivator 1 (CRTC1) mutations occurred significantly more frequently in the chemotherapy-resistant group (p = 0.027) and were associated with shorter progression-free survival (p = 0.036).Signature weighting analysis showed a significant increase in Signature.3, which is associated with homologous recombination repair deficiency in the chemotherapy-sensitive group (p = 0.045). Conversely, signatures related to effective DNA repair mechanisms, Signature.1 and Signature.15, were significantly reduced (p = 0.002 and p < 0.001, respectively). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that gene mutations were significantly enriched in the JAK-STAT signaling pathway. Conclusion This study, through intergroup comparative analysis, found that immunotherapy (using programmed death 1/programmed death-ligand 1 inhibitors) may improve the prognosis of patients with short survival and chemotherapy resistance. Additionally, the study revealed that mutations in BCL9L and WHSC1 could serve as biomarkers for breast cancer prognosis, while CRTC1 mutations and Signature.3 could predict chemotherapy response. The study also found that the JAK-STAT pathway might be a potential therapeutic target for chemotherapy resistance. Therefore, this study identifies molecular characteristics that influence the prognosis of breast cancer patients, providing important theoretical insights for the development of personalized treatment strategies.

Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.

Objective:To analyze the advantages and disadvantages of online and offline laboratory medicine continuing education and training, and to discuss the future continuing education and training mode under new technology development and new situation.Methods:A questionnaire was administered to the trainees who participated in the 2019 and/or 2020 national continuing medical education project—Clinical Application and Evaluation of New Technologies and Methods of Laboratory Medicine—sponsored by the Department of Laboratory Medicine, West China Hospital, Sichuan University. One hundred and twenty-four questionnaires were completed for the 2019 offline training, and 503 questionnaires were completed for the 2020 online training. The rank sum test, Fisher's exact test, and chi-square test were performed for statistical analysis with the use of SPSS 26.0.Results:The participants in 2020 were significantly younger and the proportion of female participants in 2020 was significantly higher compared with those in 2019. Intermediate titles or above accounted for 66.93% (83/124) in 2019, and intermediate titles or below accounted for 88.67% (446/503) in 2020. The proportion of people from Sichuan Province was significantly higher in 2019. The proportion of trainees from primary institutions was significantly lower in 2019. In 2019, public institutions were mainly tertiary hospitals (74.31%, 81/109), and the majority of participants from private institutions were from third party testing institutions (60.00%, 9/15). In 2020, the percentage of tertiary hospitals in public institutions decreased to 60.99% (258/423), while the percentage of community medical institutions increased to 10.64% (45/423), and 75.00% (60/80) of trainees from private institutions were from tertiary and secondary medical institutions. Trainees with lower educational levels were more likely to appreciate the value of the training course, especially with higher degrees of satisfaction with improvements in theoretical levels and practical skills, and participants from primary institutions believed that the training course could effectively improve their theoretical and practical levels. The number of participants who provided suggestions on laboratory medicine continuing education and training needs in 2019 (83.75%, 67/80) was higher than that in 2020 (48.51%, 244/503). The overall pass rate of post-training assessment in 2020 was 88.52% (424/479).Conclusions:Online and offline training modes have different audience groups and training effects. Online continuing education can provide training opportunities to more primary care personnel and junior and intermediate professionals, which is conducive to improving the basic professional literacy and testing skills of laboratory personnel on the whole. At the same time, the integration of online and offline modes will promote the development of laboratory medicine continuing education.

Oxalicine B ( 1) is an α-pyrone meroterpenoid with a unique bispirocyclic ring system derived from Penicillium oxalicum. The biosynthetic pathway of 15-deoxyoxalicine B ( 4) was preliminarily reported in Penicillium canescens, however, the genetic base and biochemical characterization of tailoring reactions for oxalicine B ( 1) has remained enigmatic. In this study, we characterized three oxygenases from the metabolic pathway of oxalicine B ( 1), including a cytochrome P450 hydroxylase OxaL, a hydroxylating Fe(II)/α-KG-dependent dioxygenase OxaK, and a multifunctional cytochrome P450 OxaB. Intriguingly, OxaK can catalyze various multicyclic intermediates or shunt products of oxalicines with impressive substrate promiscuity. OxaB was further proven via biochemical assays to have the ability to convert 15-hydroxdecaturin A ( 3) to 1 with a spiro-lactone core skeleton through oxidative rearrangement. We also solved the mystery of OxaL that controls C-15 hydroxylation. Chemical investigation of the wild-type strain and deletants enabled us to identify 10 metabolites including three new compounds, and the isolated compounds displayed potent anti-influenza A virus bioactivities exhibiting IC₅₀ values in the range of 4.0-19.9 μmol/L. Our studies have allowed us to propose a late-stage biosynthetic pathway for oxalicine B ( 1) and create downstream derivatizations of oxalicines by employing enzymatic strategies.

Objective To investigate radiation resources in medical diagnosis and treatment and their use frequency in medical institutions in Hangzhou, China, and to provide a basis for relevant departments to rationally allocate and scientifically supervise the resources. Methods From April 1, 2019 to March 31, 2020, a survey was conducted on the basic information, radiation staff, equipment configuration, and frequency of radiation diagnosis and treatment of all medical institutions in Hangzhou using a questionnaire. Results There were 1001 institutions with radiation services in Hangzhou, with 6714 radiation staff members and 2742 pieces of radiation equipment. The frequency of conventional X-ray diagnosis was 788.43 per 1000 population. The frequency of computed tomography diagnosis was 531.93 per 1000 population. The frequency of mammography and dental photography diagnosis was 246.34 per 1000 population. The frequency of interventional diagnosis and treatment was 10.01 per 1000 population. The frequency of radiotherapy was 2.39 per 1000 population. The frequency of nuclear medicine diagnosis was 8.90 per 1000 population. The frequency of nuclear medicine treatment was 0.99 per 1000 population. Conclusion Medical institutions have developed rapidly in Hangzhou, but with an unbalanced situation. In order to better protect the health of examinees, we recommend relevant departments optimize resource allocation and strengthen supervision on radiation protection in medical institutions.

Objective:To explore the application effect of comprehensive moxibustion therapy with Huolong Cupping in elderly patients with antibiotic-associated diarrhea.Methods:From June 2021 to February 2022, 60 elderly patients with antibiotic-associated diarrhea in the Second Affiliated Hospital of Zhejiang Chinese Medical University were selected as research objects, and divided into the observation group and the control group with 30 cases each by random number table method. The control group received Bifidobacterium treatment and routine nursing, and the observation group conducted comprehensive moxibustion therapy with Huolong Cupping on the basis of the control group. Seven days after intervention, total score of Traditional Chinese Medicine symptom, score of Gastrointestinal Quality of Life Index (GIQLI) were compared between the two groups.Results:Seven days after intervention, GIQLI score of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05) ; total score of Traditional Chinese Medicine symptom of the observation group was lower than that of the control group, and the difference was statistically significant ( P<0.01) . Conclusions:Comprehensive moxibustion therapy with Huolong Cupping can improve clinical symptoms and gastrointestinal function in elderly patients with antibiotic-associated diarrhea, and improve their quality of life.

Objective To explore the absorbed dose to the common tissues of subjects in four clinical CT scanning modes and the spatial distribution of the radiation field in chest scanning, in order to provide a basis for the radiation protection of subjects and the space in the machine room. Methods A thermoluminescence detector (TLD) was used to measure the absorbed doses to the eye lens, thyroid gland, gonad, chest and abdominal skins of the anthropomorphic phantom in four CT scanning modes. The TLD was used to monitor the air kerma at different positions from the CT diagnostic table during chest spiral scanning. Results The absorbed doses to the eye lens, thyroid gland, gonad, chest and abdominal skins of the anthropomorphic phantom in four CT scanning modes were 0.040-64.818 mGy, 0.154-10.155 mGy, 0.028-0.154 mGy, 0.443-17.141 mGy, and 0.093-14.346 mGy, respectively. The maximum air kerma value of the space radiation field during chest scanning was 0.049 mGy, and the farther the distance from the CT tube, the smaller the value. Conclusion The absorbed doses to the common tissues of subjects examined by the four CT scanning modes generally do not exceed the threshold doses. The dose received by the companion of the subject during a single chest CT scan was small. In order to minimize radiation hazards, shielding measures can be taken in CT scanning to reduce the absorbed doses to the tissues of the subject, and the companion of the subject should appropriately increase the distance from the tube and the diagnostic table.

Objective:To explore the predictive value of serum tissue inhibitor of metalloproteinases-2(TIMP-2), insulin-like growth factor-binding protein-7 (IGFBP-7), angiopoietin-2 (Ang-2) and laboratory examination indicators in patients with sepsis associated acute kidney injury (SAKI).Methods:Present study included 69 patients with sepsis, who were admitted to the emergency department of Peking University Third Hospital from April 2017 to August 2018. Within 72 hours of admission, 28 cases developed SAKI. General clinical features including sequential organ failure assessment (SOFA), acute physiological and chronic health status score Ⅱ (APACHE Ⅱ) and laboratory examination indicators including white blood cells (WBC), neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, fibrinogen (Fib), urea, uric acid (UA) were analyzed and serum samples were obtained to detect the levels of biomarkers TIMP-2, IGFBP-7, and Ang-2. Multivariate logistic regression analysis was performed to determine independent risk factors of SAKI, and the receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the early predictive value of biomarkers and laboratory examination indicators for SAKI.Results:Compared with the non-SAKI group, patients in the SAKI group had higher SOFA score, higher incidence of septic shock, higher NLR, PCT, CRP, D-dimer, and UA levels (all P<0.05). The levels of TIMP-2, IGFBP-7, TIMP-2×IGFBP-7 and Ang-2 in the SAKI group were 23.5 (17.3, 30.3)ng/ml, (185.6±47.2)ng/ml, 3.98(2.89, 6.00) (ng/ml) 2/1 000, 1 953 (950, 2 239) pg/ml respectively, which were significantly higher than those in the non-SAKI group (16.4[13.5, 22.4] ng/ml, [139.4±34.7]ng/ml, 2.28[1.57, 4.03](ng/ml) 2/1 000, 576[334, 1 076] pg/ml, respectively, all P<0.05). Logistic regression analysis showed that IGFBP-7 ( OR=1.039, 95%CI 1.000-1.079, P<0.05) and SOFA ( OR=1.521, 95%CI 1.144-2.022, P<0.05) are independent risk factors of SAKI. ROC curve analysis showed that the AUC of IGFBP-7 and SOFA scores for early prediction of SAKI was 0.805 (sensitivity 78.6%,specificity 78.3%), 0.832 (sensitivity 67.9%,specificity 82.9%) respectively. Combined both biomarkers, the AUC increased to 0.893 (sensitivity 82.1%, specificity 87.8%), the diagnostic performance was superior to IGFBP-7 or SOFA alone ( P<0.05). Conclusion:Elevated IGFBP-7 and SOFA are independent risk factors for sepsis associated acute kidney injury, and combined assessment with IGFBP-7 and SOFA can increase the diagnostic performance on the early detection of high-risk patients with SAKI.