Relationship between self-reported occupational noise exposure and expression levels of plasma inflammatory cytokines in adult asthmatic patients / 公共卫生与预防医学

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer

Abstract Objectives The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. Methods A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. Results The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035). Conclusions sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions. Level of evidence 3.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome

Background & objectives: Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Methods: Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. Results: It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. Interpretation & conclusions: This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics

Serum soluble CD40 ligand expression in children with Kawasaki disease in acute phase and its clinical significance / 中国综合临床

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.

Diagnostic value of soluble interleukin 7 receptor in combination with other biomarkers for emergency sepsis / 中国医师杂志

Objective:To investigate the diagnostic value of soluble interleukin 7 receptors (sIL-7R) in combination with other biomarkers for emergency sepsis.Methods:A prospective study method was used to select 102 emergency patients from the Chuiyangliu Hospital affiliated to Tsinghua University and Baoding First Central Hospital from December 2020 to June 2022. They were divided into sepsis group (80 cases) and non-sepsis group (22 cases), and 20 healthy people in the same period were selected as the control group. The patient data were collected, the relevant biomarker examination was improved and the values were recorded. Using statistical methods, the significance of sIL-7R for the diagnosis of sepsis was assessed, and important indicators related to the presence of sepsis were also screened to construct a model for the early diagnosis of sepsis.Results:The levels of interleukin-6 (IL-6), C-reactive protein (CRP), age and sIL-7R in sepsis group were significantly higher than those in non-sepsis group and control group (all P<0.01). Further, the sIL-7R, age, CRP, and IL-6 were selected as important diagnostic indicators of sepsis by comparing the sepsis and non-sepsis groups using R-language statistical software. Receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) for diagnosing sepsis of the four indexes were calculated as 0.759, 0.622, 0.716 and 0.640, respectively. The diagnostic model based on the four indexes performed better than other indexes, and the AUC value reached 0.869. The AUC of sIL-7R in the diagnosis of sepsis was higher than that of the other three indexes, and the detection of SIL-7R in combination with other inflammatory indexes was significantly higher than that of the four indexes, which had obvious advantages for the early diagnosis of sepsis. Conclusions:sIL-7R is a good biological marker for the early diagnosis of sepsis, and its combination with age, CRP, and IL-6 can better improve the early diagnosis of sepsis.

Change of serum D-D, sVCAM-1 and P-selectin after limb fractures surgery and their relationship with thrombosis / 中国医师杂志

Objective:To investigate the relationship between change of serum D-dimer (D-D), soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin and thrombosis after limb fracture surgery.Methods:289 patients with limb fractures who were treated in the emergency department of Shulan (Hangzhou) Hospital from January 2021 to January 2022 were selected as the study subjects. They were divided into deep vein thrombosis (DVT) group ( n=62) and non-DVT group ( n=227) according to whether DVT occurred after operation. The levels of prothrombin time (PT), activated partial prothrombin time (APTT), D-D, sVCAM-1 and P-selectin were measured before and after operation in all patients. The levels of PT, APTT, D-D, sVCAM-1 and P-selectin were compared between DVT group and non-DVT group. Logistic sequential stepwise regression analysis was used to analyze the risk factors of postoperative thrombosis in patients with limb fractures. Results:There was no statistically significant difference in PT and APTT between 289 patients with limb fractures after operation and before operation (all P>0.05), while the levels of serum D-D, sVCAM-1 and P-selectin after operation were higher than that before operation (all P<0.05). There was no significant difference in general data between DVT group and non-DVT group (all P>0.05); There was no statistically significant difference in PT and APTT before and after operation between DVT group and non-DVT group (all P>0.05). The levels of serum D-D, sVCAM-1 and P-selectin before and after operation in DVT group were higher than those in non-DVT group (all P<0.05). Logistic sequential stepwise regression analysis showed that high levels of D-D, sVCAM-1 and P-selectin were risk factors for thrombosis after limb fracture surgery (all P<0.05). Conclusions:High levels of D-D, sVCAM-1 and P-selectin are risk factors for thrombosis after limb fracture surgery.

The role of neutrophil CD 11b, soluble CD 14 subtype and mitochondrial coupling factor-6 in the risk stratification of disease outcome in neonatal sepsis and its clinical significance / 中国医师进修杂志

Objective:To investigate the role of neutrophil CD 11b (nCD 11b), soluble CD 14 subtype (sCD 14-St) and mitochondrial coupling factor-6 (CF-6) in the risk stratification of disease outcome in neonatal sepsis and its clinical significance. Methods:The clinical data of 121 septic neonates from July 2019 to March 2020 in Shanxi Children′s Hospital were retrospectively analyzed. According to the neonatal critical illness score (NCIS), the neonates were divided into non-critical group (NCIS>90 scores) with 35 cases, critical group (NCIS 70 to 90 scores) with 49 cases, very critical group (NCIS<70 scores) with 37 cases. There were 25 cases with poor prognosis (death), and 96 cases with good prognosis (survival). The C-reactive protein (CRP), procalcitonin (PCT), nCD 11b, sCD 14-St and CF-6 before treatment were detected. The correlation between nCD 11b, sCD 14-St, CF-6 and disease severity was analyzed by Spearman method; the value of nCD 11b, sCD 14-St and CF-6 in predicting poor disease outcome in sepsis neonates was analyzed by the receiver operating characteristic (ROC) curve. Results:The nCD 11b, sCD 14-St, CF-6, PCT and CRP in critical group and very critical group were significantly higher than those in non-critical group: (414.68 ± 93.29) and (532.74 ± 101.85) MFI vs. (325.45 ± 71.90) MFI, (892.40 ± 113.72) and (1 249.53 ± 95.41) ng/L vs. (784.66 ± 103.72) ng/L, (84.79 ± 28.35) and (121.66 ± 34.27) ng/L vs. (42.59 ± 13.51) ng/L, (19.24 ± 6.30) and (34.96 ± 11.95) μg/L vs. (8.89 ± 2.24) μg/L, (109.49 ± 36.77) and (247.13 ± 82.06) mg/L vs. (56.84 ± 17.25) mg/L; the indexes in very critical group were significantly higher than those in critical group, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that nCD 11b, sCD 14-St and CF-6 were positively correlated with disease severity in sepsis neonates ( r = 0.719, 0.813 and 0.823; P<0.01). The nCD 11b, sCD 14-St, CF-6, PCT and CRP in poor prognosis neonates were significantly higher than those in good prognosis neonates: (618.58 ± 146.92) MFI vs. (374.55 ± 120.03) MFI, (1 516.91 ± 194.38) ng/L vs. (828.13 ± 175.67) ng/L, (165.84 ± 25.63) ng/L vs. (62.51 ± 16.75) ng/L, (43.46 ± 10.14) μg/L vs. (20.19 ± 6.30) μg/L and (321.09 ± 94.56) mg/L vs. (88.24 ± 29.19) mg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of nCD 11b, sCD 14-St and CF-6 for predicting poor disease outcome in sepsis neonates were 0.763, 0.796 and 0.838 (95% CI 0.678 to 0.836, 0.713 to 0.864 and 0.760 to 0.899), and the AUC of combination the 2 indexes was 0.921 (95% CI 0.858 to 0.962). Conclusions:The nCD 11b, sCD 14-St and CF-6 are associated with the disease severity and prognosis in sepsis neonates, and can be used as markers for risk stratification of disease outcome and assessment prognosis.

Association of serum sRANKL and Omentin-1 levels with bone mineral density and bone metabolism in postmenopausal osteoporosis patients / 中华内分泌外科杂志

Objective:To investigate the relationship between serum soluble receptor activator of nuclear factor-κB ligand (sRANKL), Omentin-1 levels and postmenopausal osteoporosis (PMOP) .Methods:A total of 310 menopausal patients admitted to Qingdao Municipal Hospital from Jun. 2017 to Jul. 2021 were selected, including 165 patients with PMOP and 145 women with simple menopause as the control group. Serum sRANKL and Omentin-1 levels were detected by ELISA. Bone mineral density and bone metabolism indexes [N-terminal propeptide of typeⅠprecollagen (PINP), bone alkaline phosphatase (BALP), β isomer of the C-terminal telopeptide of type Ⅰ collagen (β-CTX) and osteocalcin (OC) ] were compared between the two groups. The correlation between serum sRANKL and Omentin-1 levels and bone mineral density and bone metabolism indexes in PMOP patients was analyzed by Pearson. The predictive value of sRANKL and Omentin-1 to PMOP was analyzed by ROC curve. Logistic regression analysis of the influence of multiple factors on PMOP.Results:Compared with the control group (15.62±4.41) (42.56±8.53), the serum sRANKL level (26.63±8.12) was increased and Omentin-1 level (32.32±5.52) was decreased in PMOP group ( t=14.55, P<0.001; t=12.69, P<0.001). The serum sRANKL in PMOP group was positively correlated with PINP, β-CTX and OC, while the serum Omentin-1 level was negatively correlated with the above indexes by Pearson analysis. ROC curve showed that serum sRANKL and Omentin-1 had important reference significance in predicting PMOP. Logistic regression suggested that increased sRANKL and decreased Omentin-1 were risk factors for PMOP. Conclusion:Serum sRANKL and Omentin-1 in patients with PMOP are correlated with bone mineral density and bone metabolism, and have potential as diagnostic targets of PMOP.

Expression of Tim-3 in the peripheral blood of pancreatic cancer patients and the diagnostic value in combination with serum glucose chain antigen 19-9 / 中华内分泌外科杂志

Objective:To investigate the expression of soluble T cell immunoglobulin and mucin domain-3 (Tim-3) in peripheral blood of patients with pancreatic cancer and its diagnostic value in combination with serum Carbohydrate antigen 19-9 (CA19-9) .Methods:106 newly diagnosed pancreatic cancer patients and 65 age and sex matched healthy individuals were enrolled. Tim-3 concentration was quantitatively determined by enzyme-linked immunosorbent assay (ELISA). According to the expression levels of soluble Tim-3 and serum CA19-9, a binary logistic regression model of receiver operating characteristic (ROC) curve was established to compare the diagnostic effects of serum CA19-9 and soluble Tim-3 alone or combined with the two tests.Results:The levels of soluble Tim-3 in the pancreatic cancer group were significantly higher than those in the healthy control group ( P<0.001). The expression level of soluble Tim-3 was significantly higher in patients with stage III-IV pancreatic cancer than in patients with stage I-II ( P=0.003). The AUC of soluble Tim-3 diagnosis for stage I-II pancreatic cancer was 0.856 (95%CI: 0.765 to 0.992 P<0.001), Serum CA19-9 The AUC used for the stage I-II pancreatic cancer diagnosis was 0.862 (95%CI: 0.772 to 0.926 P<0.001), The AUC for the combined diagnosis was 0.949 (95%CI: 0.880 - 0.985 P<0.001) ; In a healthy population and in patients with stage III-IV pancreatic cancer, the AUC of soluble T I I-IV pancreatic cancer in stage III was 0.927 (95%CI: 0.873 to 0.963 P<0.001), the AUC of serum CA19-9 used for the diagnosis of stage III-IV pancreatic cancer was 0.933 (95%CI: 0.881 to 0.968 P<0.001), the AUC for the combined diagnosis was 0.989 (95%CI: 0.956 to 0.999 P<0.001) . Conclusions:The combination of soluble Tim-3 and serum CA19-9 can improve the diagnostic rate of pancreatic cancer patients.

Predictive value of sCTLA-4 and RAD51C proteins for recurrence after interventional therapy for cervical cancer patients / 中华内分泌外科杂志

Objective:To analyze the predictive value of soluble cytotoxic T lymphocyte-associated antigen 4 (sCTLA-4) and RAD51 paralogous gene C (RAD51C) protein in the recurrence of cervical cancer patients after interventional therapy.Methods:A total of 107 patients with cervical cancer who underwent interventional surgery in our hospital from May. 2015 to Apr. 2019 were selected as the research group. postoperative recurrence were recorded. Another 107 patients with benign cervical disease during the same period were selected as the control group. The protein expressions of sCTLA-4 and RAD51C were compared between the two groups and patients with or without recurrence. Logistic regression was used to analyze the influencing factors of postoperative recurrence of cervical cancer patients, and a nomogram model of postoperative recurrence of cervical cancer patients was constructed and verified by calibration curve. The postoperative recurrence rate of cervical cancer patients with different sCTLA-4 and RAD51C protein expressions was compared.Results:The level of sCTLA-4 and the high expression rate of RAD51C protein in the study group were higher than those in the control group ( P<0.05). High-risk human papillomavirus positive, vascular infiltration, interstitial infiltration ≥1/2, paracterine infiltration, high expression of RAD51C protein and high SCTLA-4 level were independent risk factors for postoperative recurrence of cervical cancer ( P<0.05). High-risk human papillomavirus, vascular invasion, interstitial invasion, parametrial invasion, RAD51C protein and sCTLA-4 levels were used to construct a nomogram prediction model for postoperative recurrence of cervical cancer patients. The consistency indices were 0.610 (95% CI: 0.511-0.702), 0.616 (95% CI: 0.517-0.708), 0.640 (95% CI: 0.541-0.730), 0.609 (95% CI: 0.510-0.702), 0.728 (95% CI ranged from 0.633 to 0.809), 0.817 (95% CI ranged from 0.731 to 0.885), and the calibration curve validation showed high consistency. The net benefit rate of combined detection of sCTLA-4 and RAD51C proteins was greater than that of single detection. Conclusions:sCTLA-4 and RAD51C proteins are highly expressed in cervical cancer patients, and the high expression of both indicates that cervical cancer patients have a higher risk of recurrence after surgery. Clinically, the detection of sCTLA-4 and RAD51C protein expression can be used to screen patients with high recurrence risk.

sPD-1 and changes of lymphocyte subsets in predicting the prognosis of patients with sepsis: a prospective cohort study / 中华急诊医学杂志

Objective:To observe the dynamic changes of soluble programmed cell death protein 1 (sPD-1) and cellular immunity and humoral immunity in patients with sepsis and septic shock, and to explore the relationship between sPD-1 and immunosuppression in sepsis.Methods:This study was a prospective cohort study. Patients with sepsis and septic shock admitted to the ICU of General Hospital of Ningxia Medical University from June 2018 to December 2018 were included as the study subjects, ordinary postoperative patients admitted to the ICU during the same period were included as the non-sepsis group, and healthy volunteers matched in age and sex were included as healthy controls. The sPD-1, lymphocyte count, serum immunoglobulin and lymphocyte subsets of peripheral blood on the first, third and seventh days after admission to the ICU were detected. The changes of sPD-1 and various immune indices in each group were compared, and the correlation between the indices was analyzed. For healthy controls and non-sepsis patients, only blood samples were tested on the day of inclusion.Results:A total of 90 patients [58 males and 32 females, aged (58.36±17.46) years] were included in this study, including 29 cases of sepsis, 31 cases of septic shock, 15 cases of non-sepsis, and 15 volunteers were recruited as healthy control group. The 28-day fatality rate of patients in the sepsis and septic shock groups was 28.3%. On the first day of ICU admission, the sPD-1 concentration were significantly higher in the septic shock group and sepsis group than those in the non-sepsis group and healthy control group [512.64 (216.85, 1039.41) pg/mL vs. 261.90 (191.96, 421.99) pg/mL vs. 191.56 (151.26, 232.66) pg/mL vs. 200.51 (162.14, 241.26) pg/mL, all P<0.05]. The sPD-1 concentration in the septic shock group was significantly higher than that in the sepsis group, and this phenomenon persisted for at least one week ( P<0.05). The lymphocyte count on the first day in the sepsis and septic shock groups were significantly lower than those in the healthy control and non-sepsis groups (all P<0.05), and the lymphocyte count in the septic shock group remained lower levels until the seventh day of ICU admission (all P<0.05). The percentage of lymphocytes and total T lymphocytes in the sepsis and septic shock groups were significantly lower than those in the healthy control and non-sepsis groups (all P<0.05), while the percentage of total B lymphocytes did not differ between groups (all P>0.05). The percentage of CD8+ T lymphocytes on the seventh day of ICU admission in the septic shock group was still significantly lower than that in the sepsis group [(18.36±2.23)% vs. (28.28±2.97)%, P<0.05]. The levels of serum immunoglobulin IgG and IgM were significantly lower in the sepsis and septic shock group than those in the healthy control and non-sepsis groups (all P<0.05), and the IgG and IgM in the sepsis and septic shock groups returned to normal on the seventh day of ICU admission. The area under the ROC curve was used to evaluate the predictive value of sPD-1 on poor prognosis, and the results showed that sPD-1 on the seventh day of ICU had a good predictive value for 28-day prognosis in patients with sepsis and septic shock, and the best cut-off value was 286.52 pg/mL, with a sensitivity of 100.00% and specificity of 56.25%. Conclusions:Immunosuppression occurs in patients with sepsis and septic shock in the early stage, and the duration of immunosuppression in patients with septic shock is prolonged, but humoral immunosuppression plays a major defense in the early stage, and cellular immunosuppression is dominant in the later stage.

Comparative study on the methods to determine disintegration time of oral soluble films / 药学学报

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Effects of soluble glycoprotein 130 on expression of p-STAT3 and vascular endothelial growth factor-A in retina of mice with diabetes mellitus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P<0.01). The expression of p-STAT3 and VEGF-A in sgp130 group were lower than those in DM group(all P<0.01).CONCLUSION: The sgp130 can selectively antagonize the trans signal transduction pathway of IL-6, down-regulate the expression of downstream inflammatory factors VEGF-A, and it may be used in the intervention of retinal inflammatory damage related with IL-6 in DM.

Study on preparation，characterization and in vitro transdermal properties of Xiongzhi shigao decoction soluble microneedles / 中国药房

OBJECTIVE To prepare Xiongzhi shigao decoction soluble microneedles， characterize it and investigate its transdermal properties in vitro. METHODS Two-step centrifugal method was used to prepare Xiongzhi shigao decoction soluble microneedles. The formability and mechanical property of the microneedles were evaluated from aspects of stroma fluidity， microneedle formability， needle hardness， etc. The appearance， mechanical strength， dissolution performance， skin barrier recovery performance and drug loading of the prepared microneedles were characterized by using active components of the soluble microneedle （chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide， isoimperatorin） as indicators. The in vitro transdermal performance was investigated by Franz diffusion cell. RESULTS The soluble microneedle tips of Xiongzhi shigao decoction prepared in this study were conical， evenly distributed and of the same thickness， with good mechanical properties； the tip of the needle could be almost completely dissolved after being penetrated into the skin of rats for 2 hours， and the skin barrier recovery performance was good； the drug loading of chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide and isoimperatorin were （87.04±1.12）， （67.69±1.23）， （20.65±0.17）， （35.00±0.11）， （153.83±0.21） and （23.52±0.50） μg per patch respectively. The results of in vitro transdermal study showed that cumulative release rates of 6 active components in this microneedle after 72 hours were 36.94%， 56.72%， 19.36%， 57.98%， 11.06% and 35.19%， respectively. CONCLUSIONS Xiongzhi shigao decoction soluble microneedles are prepared successfully in this study and have good formability， mechanical properties and pliable backing， which can significantly promote the transdermal drug delivery.

Expression and clinical significance of interferon regulatory factor 4 and soluble suppression of tumorigenesis 2 in conjunctival epithelial cells and tears of patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and clinical significance of interferon regulatory factor 4(IRF4)and soluble suppression of tumorigenesis 2(sST2)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: A total of 94 patients with dry eye who admitted to our hospital from January 2019 to December 2021 were selected as the dry eye group, and 97 physical examiners who underwent ophthalmic examination were selected as the control group at the same time. The conjunctival epithelial cells and tears of the subjects were collected, and the clinical indicators, including tear film break-up time(BUT), corneal fluorescein staining(CFS)score, and Schirmer Ⅰ test(SⅠt)were recorded. The levels of IRF4 and sST2 in conjunctival epithelial cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR), and the levels of IRF4 and sST2 in tears were detected by enzyme-linked immunosorbent assay(ELISA). Pearson method was used to analyze the correlation between IRF4 and sST2 levels in conjunctival epithelial cells and tears and clinical indicators of dry eye patients.RESULTS: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears in dry eye group before treatment were significantly higher than those in control group(P&#x003C;0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients at 4wk after treatment were significantly lower than those before treatment(P&#x003C;0.001). The BUT and SⅠt of dry eye patients increased significantly at 4wk after treatment, and the CFS score decreased significantly(P&#x003C;0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients before treatment were positively correlated with CFS score before treatment and negatively correlated with BUT and SⅠt before treatment(P&#x003C;0.001).CONCLUSION: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of patients with dry eye are increased, and are significantly correlated with BUT, SⅠt and CFS scores, which has potential to become a new therapeutic target for dry eye.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Study on the correlation between color and inner quality during the processing of Prunus mume carbon and its processing end point / 中国药房

OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.

Serum levels of soluble programmed death-1 and soluble programmed death-ligand 1 in chronic hepatitis B patients with clinical cure and their clinical features / 临床肝胆病杂志

Objective To investigate the serum levels of soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in chronic hepatitis B (CHB) patients with clinical cure, the correlation between programmed death-1 (PD-1) and lymphocytes by flow cytometry, and the recovery of hepatitis B virus (HBV)-specific immunity. Methods A total of 26 CHB patients with clinical cure, 26 treatment-naïve CHB patients, and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled, and related clinical data and peripheral blood samples were collected. ELISA was used to measure the serum levels of sPD-1 and sPD-L1, and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes. CHB patients with clinical cure were compared with the treatment-naïve CHB patients and the healthy controls. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the chi-square test was used for comparison of categorical data between groups. The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables. Results For the 26 CHB patients with clinical cure, the mean time of antiviral therapy was 8.33 years, with entecavir as the antiviral drug. The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls ( P 0.05). Conclusion The serum levels of sPD-1 and sPD-L1 in treatment-naïve CHB patients are mainly associated with exhausted CD8 + T cells in peripheral blood, while there is no significant correlation between serum sPD-1/sPD-L1 and exhausted CD8 + T cells in peripheral blood in CHB patients with clinical cure.

Functional analysis on sucrose transporters in sweet potato / 生物工程学报

Sweet potato is an important food crop that can also be used as an industrial raw material. Sucrose is the main form of long-distance carbohydrate transport in plants, and sucrose transporter (SUT) regulates the transmembrane transport and distribution of sucrose during plant growth and metabolism. Moreover, SUT plays a key role in phloem mediated source-to-sink sucrose transport and physiological activities, supplying sucrose for the sink tissues. In this study, the full-length cDNA sequences of IbSUT62788 and IbSUT81616 were obtained by rapid amplification of cDNA ends (RACE) cloning according to the transcripts of the two SUT coding genes which were differentially expressed in sweet potato storage roots with different starch properties. Phylogenetic analysis was performed to clarify the classification of IbSUT62788 and IbSUT81616. The subcellular localization of IbSUT62788 and IbSUT81616 was determined by transient expression in Nicotiana benthamiana. The function of IbSUT62788 and IbSUT81616 in sucrose and hexose absorption and transport was identified using yeast functional complementarity system. The expression pattern of IbSUT62788 and IbSUT81616 in sweet potato organs were analyzed by real-time fluorescence quantitative PCR (RT-qPCR). Arabidopsis plants heterologous expressing IbSUT62788 and IbSUT81616 genes were obtained using floral dip method. The differences in starch and sugar contents between transgenic and wild-type Arabidopsis were compared. The results showed IbSUT62788 and IbSUT81616 encoded SUT proteins with a length of 505 and 521 amino acids, respectively, and both proteins belonged to the SUT1 subfamily. IbSUT62788 and IbSUT81616 were located in the cell membrane and were able to transport sucrose, glucose and fructose in the yeast system. In addition, IbSUT62788 was also able to transport mannose. The expression of IbSUT62788 was higher in leaves, lateral branches and main stems, and the expression of IbSUT81616 was higher in lateral branches, stems and storage roots. After IbSUT62788 and IbSUT81616 were heterologously expressed in Arabidopsis, the plants grew normally, but the biomass increased. The heterologous expression of IbSUT62788 increased the soluble sugar content, leaf size and 1 000-seed weight of Arabidopsis plants. Heterologous expression of IbSUT81616 increased starch accumulation in leaves and root tips and 1 000-seed weight of seeds, but decreased soluble sugar content. The results obtained in this study showed that IbSUT62788 and IbSUT81616 might be important genes regulating sucrose and sugar content traits in sweet potato. They might carry out physiological functions on cell membrane, such as transmembrane transport of sucrose, sucrose into and out of sink tissue, as well as transport and unloading of sucrose into phloem. The changes in traits result from their heterologous expression in Arabidopsis indicates their potential in improving the yield of other plants or crops. The results obtained in this study provide important information for revealing the functions of IbSUT62788 and IbSUT81616 in starch and glucose metabolism and formation mechanism of important quality traits in sweet potato.

Quality evaluation methods of Poria based on yield and content of alkali extracted polysaccharide / 中国中药杂志

To improve the quality control methods of Poria and develop and utilize its resources fully, alkaline extraction was used in this study to determine the yield and content of alkali-soluble polysaccharides of Poria. The alkali-soluble extracts of Poria were obtained according to the optimum extraction conditions on the basis of single-factor test, and 30 batches of samples were determined. The structure and chemical composition of the alkali-soluble extracts was characterized by high-performance gel permeation chromatography(HPGPC), Fourier transform infrared spectrometry(FT-IR), nuclear magnetic resonance(NMR) spectroscopy and high-performance liquid chromatography(HPLC) with 1-phenyl-3-methyl-5-pyrazolone(PMP-HPLC). The results showed that the content of the alkali-soluble extracts was in the range of 46.98%-73.86%. The main component was β-(1→3)-glucan, and its molecular mass was about 1.093×10~5. Further, the content of alkali-soluble polysaccharides of Poria was measured by UV-Vis spectrophotometry and HPLC coupled with the evaporative light scattering detector(HPLC-ELSD), and 30 batches of samples were measured. The results indicated that the content of alkali-soluble polysaccharides determined by UV-Vis spectrophotometry was in the range of 73.70%-92.57%, and the content of samples from Hubei province was slightly higher than that from Yunnan province, Anhui province and Hunan province. The content of alkali-soluble polysaccharides determined by HPLC-ELSD was in the range of 51.42%-76.69%, and the samples from Hunan province had slightly higher content than that from the other three provinces. The content determined by UV-Vis spectrophotometry was higher than that by HPLC-ELSD. However, the content determined by HPLC-ELSD was close to that of alkali-soluble extract, which could accurately characterize the content of alkali-soluble polysaccharides in Poria, and the method was simple and repeatable. Therefore, it is recommended that the quantitative analysis method for alkali-soluble extract and alkali-soluble polysaccharides by HPLC-ELSD be used in the quality standards of Poria in Chinese Pharmacopeia.