Objective To investigate the expression and clinical significance of heat shock protein family A member 5(HSPA5)and apolipoprotein B mRNA editing enzyme catalytic polypeptide-like protein 3B(APO-BEC3B)in high-risk human papillomavirus(HR-HPV)positive cervical cancer patients.Methods A total of 86 patients with HR-HPV positive cervical cancer tissues diagnosed and treated in Zhuhai Integrated Tradi-tional Chinese and Western Medicine Hospital from March 2019 to March 2021 were retrospectively collected as the case group,50 cases of HR-HPV negative cervical cancer patients tissues diagnosed and treated during the same period were selected as the case control group,and 50 cases of normal cervical tissues from patients undergoing total hysterectomy were selected as the benign control group during the same period.The protein expressions of HSPA5 and APOBEC3B were analyzed by immunohistochemistry.The expressions of HSPA5 mRNA and APOBEC3B mRNA were detected by real-time fluorescence quantitative PCR.Kaplan-Meier sur-vival curve was used for survival analysis,and Cox proportional hazards regression model was used to analyze the prognostic factors of HR-HPV positive cervical cancer patients.Results The expressions of HSPA5 mR-NA and APOBEC3B mRNA in the case group were higher than that in the case control group and benign con-trol group,and the difference was statistically significant(P＜0.05).The positive expressions of HSPA5 pro-tein and APOBEC3B protein in the case group were higher than those in the case control group and the benign control group,and the difference was statistically significant(P＜0.05).Compared with FIGO stage Ⅰ A-Ⅰ B and without lymph node metastasis,the positive rates of HSPA5 and APOBEC3B proteins in HR-HPV positive cancer tissues with FIGO stage Ⅱ A and lymph node metastasis were higher,and the difference was statistically significant(P＜0.05).The 3-year survival rate of HSPA5 protein positive group was 68.52％(37/54),which was lower than that of HSPA5 protein negative group(87.50％,28/32),and the difference was statistically significant(Log Rank x2=4.103,P=0.043).The 3-year survival rate of APOBEC3B protein positive group was 67.31％(35/52),which was lower than that of APOBEC3B protein negative group(88.24％,30/34),and the difference was statistically significant(Log Rank x2=5.241,P=0.022).FIGO stage(HR=1.570,95％CI:1.038-2.374),lymph node metastasis(HR=1.754,95％CI:1.109-2.775)and HSPA5 protein(HR=1.616,95％CI:1.154-2.265)and APOBEC3B protein(HR=1.449,95％CI:1.095-1.918)in cancer tissues were independent factors affecting the prognosis of HR-HPV positive cervical cancer(P＜0.05).Conclusion HSPA5 and APOBEC3B mRNA and protein levels are significantly increased in HR-HPV positive cervical cancer.The protein expression of HSPA5 and APOBEC3B is related to the pro-gression and prognosis of patients with HR-HPV positive cervical cancer,which is a new prognostic marker for evaluating the prognosis of HR-HPV positive cervical cancer.

Objective:To investigate the correlation of peripheral blood 25-hydroxyvitamin D3 [25 (OH) D3] level with T cell subsets in multiple myeloma (MM).Methods:The clinical data of 11 newly diagnosed MM patients hospitalized in Heze Municipal Hospital and the First People's Hospital of Jining from June 2019 to June 2021 were retrospectively analyzed, and 8 healthy people were selected as the healthy control group. The patients achieved disease remission after 4 courses of BD (bortezomib + dexamethasone) regimen. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure the peripheral blood 25-(OH) D3 level in MM patients at initial diagnosis and after 4 courses of treatment, as well as people in the healthy control group. The proportion of peripheral blood helper T cell (Th) 1, Th2, Th17, and regulatory T cells (Treg cells) in CD3 + CD8 + T cells was measured by using flow cytometry. IgA, IgG, IgM, lactic dehydrogenase (LDH), β 2-microglobulin (β 2-MG) levels were analyzed by using fully automatic biochemical analyser. Cytoanalyze was used to detect the hemoglobin level in the peripheral blood. The differences of all indicators in MM patients at initial diagnosis, remission after treatment and the healthy control group were compared. Pearson method was used to analyze the correlation of the peripheral blood 25-(OH) D3 level with T cell subsets and other biochemical indicators in MM patients at initial diagnosis and remission after treatment. Results:Compared with the healthy control group, the peripheral blood 25-(OH) D3 level, Th1-to-Th2 ratio (Th1/Th2), the proportion of Treg cells were all decreased (all P < 0.01), and Th17-to-Treg cells ratio (Th17/Treg) was increased ( P = 0.002). The proportion of Th17 and Th17/Treg in MM patients achieving remission after treatment was higher than that in the healthy control group (all P < 0.05); the proportion of Treg cells in MM patients achieving remission after treatment was lower than that in the healthy control group ( P = 0.010); 25-(OH) D3 level in MM patients achieving remission after treatment was lower than that in the healthy control group, while the difference was not statistically significant ( P = 0.060). The peripheral blood IgM in MM patients at initial diagnosis and those achieving remission after treatment was lower than that in the healthy control group (all P < 0.01); the levels of LDH and β 2-MG in MM patients at initial diagnosis and those achieving remission after treatment was higher than that in the healthy control group (all P < 0.05). The peripheral blood 25-(OH) D3 level in MM patients at initial diagnosis was positively correlated with the proportion of Th1, Th1/Th2 ( r values 0.89, 0.60, all P < 0.05), and negatively correlated with the proportion of Th17 and Th17/Treg ( r values -0.61, -0.75, all P < 0.05). After treatment, there was no correlation of the proportion of Th1, Th2, Th17, Treg, Th1/Th2, Th17/Treg with peripheral blood 25- (OH) D3 level for patients achieving remission ( r values were -0.36, -0.45, -0.10, 0.10, 0.19, 0.03, all P > 0.05). IgM, LDH, β 2-MG was negatively correlated with 25- (OH) D3 level in the peripheral blood of MM patients at initial diagnosis ( r values were -0.76, -0.71, -0.62, all P < 0.05); while there was no correlation of 25-(OH) D3 level with IgA, IgG, IgM, LDH, β 2-MG, hemoglobin for patients achieving remission after treatment ( r values were -0.36, 0.19, -0.09, 0.47, 0.47, -0.11, all P > 0.05). Conclusions:MM patients show the decreased peripheral blood 25-(OH) D3 level, the increased Th17 and the decreased Treg cells; 25-(OH) D3 level is related to the imbalance of Th1/Th2/Th17/Treg, which suggests that 25-(OH) D3 may be related to the development, progression, prognosis and abnormal immune responses in the body of MM.

Background::Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters.Methods::A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model.Results::In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found ( P = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) ( F = 1.268; P = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%. Conclusions::eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （P<0.01）， nucleic acids significantly increased expression of lung tissue in mice （P<0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （P<0.05，P<0.01）， lung tissue cells in the immune factor TNF-α， IL-10 and IL-6 were significantly increased （P<0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （P<0.01）. Compared with model group， in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower （P<0.01）， the lung tissue of mice express nucleic acid decreased significantly （P<0.01）， MTL content decreased significantly （P<0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-α， IFN-γ levels were significantly lower （P<0.01）， in vitro cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （P<0.05）， in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.

Objective:To explore benefit finding and its influencing factors among enterostomy patients.Methods:A total of 120 enterostomy patients were investigated with general information questionnaire, Benefit Finding Scale, Simplified Scale of Resilience and Perceived Social Support Scale.Results:The score of benefit finding among enterostomy patients was 49.44±5.86. Multiple regression analysis showed that education level, self-care, complications, resilience, perceived social support were influencing factors of benefit finding, and explained 51.1% of the variance.Conclusions:The benefit finding among enterostomy patients was grim. It is suggested that clinical staff pay more attention to the patients with low education, poor self-care and complications of stoma, and also pay more attention to the positive psychology and the social support system of patients, guide patients to pay attention to the positive significance of the disease, so as to improve the level of benefit finding.

Objective:To investigate the current situation with regard to a sense of coherence in major caregivers of enterostomy patients and analyze its relationship with self-efficacy and perceived social support.Methods:From July to December 2019, a total of 118 major caregivers of enterostomy patients were investigated using a general information questionnaire, a self-efficacy scale, and a perceived social support scale.Results:The score of sense of coherence in major caregivers of enterostomy patients was 58.40±9.17, and the average scores of all dimensions, from high to low, were “controllable sense，” “understandable sense，”and “meaningful sense.” Sense of coherence was positively correlated with self-efficacy and perceived social support ( r=0.457, P<0.01; r=0.369, P<0.01). Hierarchical multiple regression analysis showed that self-efficacy and perceived social support had a positive predictive effect on sense of coherence and explained 35.2% of the variance ( R′ 2=0.352, F=25.639, P<0.001). Conclusions:The main caregivers of enterostomy patients had a low level of sense of coherence. Self-efficacy and perceived social support have a positive effect on sense of coherence. Medical staff should take targeted measures to help caregivers improve their self-efficacy and social support system in order to improve their sense of coherence.

Objective:To investigate the clinical efficacy and related adverse reactions of ixazomib-based chemotherapy regimens in the treatment of relapsed/refractory multiple myeloma (RRMM).Methods:Twenty-one patients with RRMM who received ≥2 courses of ixazomib-based chemotherapy regimens in Heze Municipal Hospital and Zoucheng People's Hospital of Shandong Province from October 2018 to February 2020 were collected. Among them, 15 patients had previously received the bortezomib-based regimens, 10 patients had received the lenalidomide-based regimens, and 6 patients had received the treatment regimens containing the above two drugs. The patients were treated by a two-drug or three-drug regimen: 4 mg ixazomib was taken orally on day 1, 8 and 15 in combination with other drugs (dexamethasone, cyclophosphamide or lenalidomide). The therapeutic efficacy and safety were evaluated after the 2nd and the 4th treatment cycles.Results:The overall response rate (ORR) of 21 patients with RRMM after 2 treatment cycles was 38.09% (8/21), including 6 cases of partial remission (PR) and 2 cases of very good partial remission (VGPR). After 4 cycles, ORR was 57.14% (12/21), including 7 cases of PR, 4 cases of VGPR, and 1 case of complete remission (CR). The incidence of grade 3-4 adverse reactions of the ixazomib-based chemotherapy regimens was 23.81% (5/21). Hematological adverse reactions included neutropenia, thrombocytopenia and anemia, and other common adverse reactions included the digestive tract reactions, fatigue, hypokalemia, etc., and the peripheral nerve adverse reactions were all grade 2 or below grade 2.Conclusion:The ixazomib-based chemotherapy regimens are effective and safe in treating RRMM.

Objective:To explore rumination status and its influencing factors among enterostomy patients, so as to provide references for the formulation of interventions.Methods:Using convenience sampling method, 120 patients with enterostomy who were treated and followed up in the Fifth Affiliated Hospital of Sun Yat-Sen University from July to December 2019 were selected as the research subjects. General information questionnaire, Event Related Rumination Inventory Scale, Simplified Scale of Resilience and Perceived Social Support Scale were applied in the investigation.Results:The invasive rumination score of enterostomy patients was (13.64±4.88) and the purposive rumination score was (14.90±3.72) . Multiple linear regression analysis showed that age, self-care degree of stoma, resilience and perceived social support explained 38.1% of the variance of invasive rumination ( P<0.01) . Education, occupation, resilience and perceived social support explained 41.9% of the variation of invasive rumination ( P<0.01) . Conclusions:The rumination of enterostomy patients was in the lower middle level. It is suggested that clinical staff pay more attention to the patients with low age, poor self-care ability of colostomy, low education level and unemployed state. At the same time, measures should be taken to improve the level of patients' resilience and improve their social support system, so as to promote the patients' positive psychological adjustment.

Objective:To observe the clinical efficacy and adverse reactions of bortezomib once-weekly therapy for newly diagnosed multiple myeloma (MM).Methods:The clinical data of 50 patients with newly diagnosed MM who received bortezomib combined with chemotherapy in Heze Municipal Hospital of Shandong Province from June 2016 to June 2019 were retrospectively analyzed. The patients were divided into once-weekly medication regimen (the observation group, 21 cases) and twice-weekly medication regimen (the control group, 29 cases). The efficacy and adverse reactions of both groups were compared.Results:The total effective rate of the former 2 treatment courses in the observation group was lower than that in the control group, and the difference was statistically significant [23.8% (5/21) vs. 55.2% (16/29), χ 2 = 4.918, P = 0.027]. After treatment of 4 and 6 courses, there were no statistically significant differences in the total effective rate between the observation group and the control group [66.7% (14/21) vs. 72.4% (21/29); 81.0% (17/21) vs. 86.2% (25/29), all P > 0.05]. The incidence of peripheral neuropathy in the observation group was lower than that in the control group, and the difference was statistically significant [14.3% (3/21) vs. 41.4% (12/29), χ 2 = 4.416, P = 0.036]. There was no statistically significant difference in the incidence of other adverse reactions of both groups (both P < 0.05). Conclusions:The therapeutic effect of once-weekly medication regimen is similar to that of twice-weekly medication regimen for the treatment of newly diagnosed MM. The incidence of peripheral neuropathy in the once-weekly therapy is low and the patients can have better tolerance.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.