Objective: To understand the pathogen spectrum composition of non-bacterial respiratory infections in Pinghu City, Zhejiang Province, so as to provide insights for the prevention and control of respiratory infectious diseases. Methods: A total of 592 throat or nasopharynx swab samples were collected from fever patients in Pinghu First People's Hospital from Jamuary 2021 to November 2022. Multiple real-time fluorescence quantitative polymerase chain reaction was used to detect the nucleic acids of rhinovirus (RhV), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), metapneumovirus (MPV), coronavirus (CoV), Boca virus (Boca), enterovirus (EV), influenza virus (Flu), chlamydia pneumoniae (CP) and mycoplasma pneumoniae (MP). The detection rates of pathogens and mixed infections in different age groups and seasons were analyzed. Results: A total of 212 samples were tested positive for at least one pathogen's nucleic acid from 592 samples, with a total detection rate of 35.81%. The detection rates of RhV (9.80%), PIV (7.26%), Flu (6.76%), RSV (4.39%) and CoV (3.72%) were relatively high. The detection rates were higher among patients at ages of 0 to 2 years and 3 to 17 years than among patients at ages of 18 to 59 years, and in autumn than in spring and winter (all P<0.05). Twenty-three samples were infected by mixed pathogens, accounting for 3.89%. The mixed infections were all detected two pathogens, with PIV, CoV, RhV, and ADV predominant. Conclusions From 2021 to November 2022, the main pathogens of non-bacterial respiratory infections in Pinghu City were RhV, PIV, FLu, RSV and CoV, and there were mixed infections. It is necessary to strengthen the prevention and control of respiratory infection in infants and children.

Objective To evaluate the effcacy of electron-beam chest-wall irradiation in patients with breast cancer after mastectomy.Methods From June 1999 to December 2007,280 women with localized breast cancer received postmastectomy radiotherapy using electron beam to chest wall.The effcacy and toxicity of these 280 women was compared with 118 women treated during the same period using tangential field with photon beam.Results The follow-up rate was 93.2%.140 patients had a minimum followed up time of 5 years and 12 patients had a minimum follow up time of 10 years.The 5-year and 10-year chest wall recurrence rates were 6.8%and 5.0%.14.8%and 10.1%for patients irradiated with electron and photon(X2=1.12,P=0.290).The corresponding 5-year and 10-year disease-free survival rates were 60.6%and 65.5%,47.6%and 57.3%(X2=0.97,P=0.325).The 5-year and 10-year overall survival rates were 77.5%and 79.6%,48.4%and 53.3%(X2=0.37,P=0.545).Grade Ⅱ or more acute skin toxicity occurred in 10.4%and 16.9%of patients irradiated with electron and photon(X2=3.34.P=0.090).Pulmonary fibrosis developed in 28.8%and 22.1% of patients irradiated with electron and photon(X2=1.27,P=0.300).Conclusion Electron-beam chest-wall irradiation is as effective as photon-beam irradiation in breast cancer after mustectomy.

Objective To analyze the prognosis of T1-T2 stage breast cancer with 1 -3 positive axillary nodes after mastectomy, and to explore a subgroup of patients who could benefit from adjuvant radiotherapy. Methods In the retrospective study of 412 eligible patients, survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Log-rank method and Cox regression analysis, respectively. Results The follow-up rate was 98. 7%. 215 and 41patients were followed up for 5 and 10 years,respectively. The 5-and 10-year overall survival (OS) rate was 90. 0% and 81.3%, respectively. The 5-and 10-year locoregional recurrence (LRR) rate was 10. 7% and 18. 6%, respectively. In univariate analysis, T2 statging, more than one positive node, hormone receptornegative ( ER&PR-negative), ratio of positive lymph nodes (LNR) ＞ 25%, Her-2 positive, no hormonal therapy were associated with a significantly higher rate of LRR. T2 staging, more than one positive node,hormone receptor-negative were the risk factors for LRR with statistical significance in the multivariate analysis. Basing on these 3 risk factors, the high-risk group (with 2 -3 factors) had a 10-year LRR rate of 36. 9% compared with 3.9% in the low-risk group ( with 0 - 1 factors;x2 =20. 64,P =0. 000). The 5-year and 10-year distant metastasis (DM) rate was 12.9% and 24. 5%, respectively. LRR, and LNR ＞25%were statistically significant predictors of DM in the multivariate analysis. The 5-year DM rate for patients with LRR was 36. 6% compared with 9. 7% without LRR (x2 = 16. 34,P =0. 000). The 5-year OS rate for patients with LRR was 69. 9% compared with 92. 9% without LRR ( x2 = 20. 79, P = 0. 000). LRR was associated with a higher risk of distant metastasis and worse survival. Conclusions LRR after mastectomy has a significant impact on the outcome of patients with T1 -T2 breast cancer and 1 - 3 positive axillary nodes.Patients who have 2 -3 risk factors might benefit from radiotherapy.

Objective To study the effect of laparoscopic myomectomy on the curative effect and postoperative rehabilitation of patients with uterine fibroids (UM).Methods From March 2014 to March 2016, selected 84 patients with UM in the people's hospital of Baoding Xushui district were divided into observation group (n=43) and control group(n=41) according to the different operation procedures, the observation group were treated with laparoscopic myomectomy and the control group were treated with open uterine fibroids.Serum T cell subsets (CD4+, CD8+, CD4+/ CD8+) between the two groups before and 1 day after operation were compared, and CA125, Cor, IL-1β levels, and surgery condition, postoperative recovery, complicationsand postoperative 12 months of recurrence were statistically compared.Results The serum CD4+, CD8+, CD4+/CD8+ levels in the observation group were significantly higher than those in the control group at 1 day after operation, the difference was statistically significant (P<0.05);the first exhaust time and hospitalization of the observation group were significantly shorter than those of the control group, and the intraoperative blood loss and postoperative pain score (VAS) were significantly lower than those in the control group (P<0.05);The incidence of postoperative complications in the observation group (6.98%, 3/43) was significantly lower than that in the control group (26.83%, 11/41), by follow-up, the recurrence rate (2.33%, 1/43) was lower than that of the control group (19.51%, 8/41), the difference was statistically significant (P<0.05).Conclusion Treatment of uterinemyoma using laparoscopic myomectomy gets a significant effect, and the body inflammation, stress response lighter and the effect of immune function is small, which can reduce the postoperative complications and recurrence rate and promote the rehabilitation of patients, and less impact on immune function.

PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Cell Line ; Disease-Free Survival* ; Drug Therapy ; Humans ; In Vitro Techniques ; Methods ; Neoadjuvant Therapy ; Paclitaxel ; Porifera ; Prognosis ; Retrospective Studies ; RNA, Long Noncoding

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD^-) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD^- rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD^- status. ②The 2-year PFS rate of patients with MRD^- status was significantly higher than that of MRD⁺ status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD⁺) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD^- status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD^-status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD^- status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD^- duration (median MRD^- duratio: 25 months vs 10 months, P=0.034) . Conclusion Our findings supported MRD⁺ status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD^- status also played a significant role in evaluation of prognosis, while loss of MRD^-status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

Objective To investigate short-term clinical efficacy of autologous leukocyte-poor platelet-rich plasma(LP-PRP)treatment of knee osteoarthritis(KO A).Methods 85 cases of patients with Keligren Lawrence grade Ⅰ-Ⅲ knee os-teoarthritis in Peking University First Hospital Taiyuan Hospital(Taiyuan Central Hospital)from 2022 to 2023 were collect-ed for autologous LP-PRP collection and quality assessment using a blood component separator,and all patients were treated with autologous LP-PRP.The degree and function of knee pain were assessed by visual analog scale(VAS)and knee arthri-tis index scale(WOMAC)at 1,3 and 6 months after injection.Knee MRI was performed after 6 months of treatment,and the MRI imaging changes before and after treatment were compared.Different influencing factors in the treatment results were grouped and analyzed,mainly including platelet concentration in LP-PRP and K-L grading of knee joint.According to the platelet concentration in LP-PRP,it was divided into three grades,which are low concentration[(＜800)×109/L],medium concentration[(800-1 000)×109/L],and high concentration[(＞1 000)× 109/L];According to the K-L grade of the knee joint,the severity of knee osteoarthritis was divided into three grades:Ⅰ、Ⅱ、Ⅲ.Results The VAS and WOMAC scores at 1,3 and 6 months after LP-PRP treatment were significantly lower than those before treatment,and the difference was sta-tistically significant(P＜0.05).There was a statistically significant difference in the therapeutic effect of different levels of platelet concentration,and when the platelet concentration was more than 1 000×109/L,the significant effect was the most obvious(P＜0.05).The therapeutic effect of different levels of platelet concentration was statistically significant(P＜0.05).MRI showed that the articular cartilage signal was significantly improved after treatment.Conclusion Autologous LP-PRP injection into knee cavity for the treatment of KO A has a good short-term clinical effect in relieving knee pain.

Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective To investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells(HSC).Methods Pathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis(S1-S4)and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy,and immunohistochemistry was used to measure the protein expression levels of PERK,eIF2α,and C/EBP homologous protein(CHOP).Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin(0,125,250,500,and 1 000 nmol/L),and qRT-PCR was used to measure the mRNA expression level of PERK,while Western blot was used to measure the protein expression levels of PERK,inositol requiring protein 1(IRE1),activating transcription factor 6(ATF6),CHOP,and α-smooth muscle actin(α-SMA).The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group;qRT-PCR was used to measure the mRNA expression levels of PERK,eIF2α,and α-SMA,Western blot was used to measure the protein expression levels of PERK,phosphorylated eIF2α(p-eIF2α),and α-SMA,and immunofluorescence assay was used to measure the expression of collagen type Ⅰ alpha 1(COL1A1).The independent samples t-test was used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.Results Compared with normal liver tissue,the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK,eIF2α,and CHOP(Z=-3.56,t=-5.75,Z=-3.52,all P<0.001).Compared with the solvent group,the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK,CHOP,IRE1,ATF6,and α-SMA(all P<0.05).Compared with the control group,the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK,eIF2α,and α-SMA and the protein expression levels of PERK,p-eIF2α,and α-SMA(all P<0.05),and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group(P<0.05).Conclusion PERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells,suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.