Objective To construct a risk prediction model of pulmonary involvement based on chest CT and clinical feature in patients with primary Sjogren's syndrome(pSS),and to explore the risk prediction value of the model.Methods A total of 360 pSS patients who had been treated at Handan Hospital of Traditional Chinese Medicine from October 2020 to August 2023 were retrospectively selected as study objects,and were then divided into a modeling group(252 patients)and a verification group(108 patients)according to a ratio of 7∶3.The patients in the modeling group were divided into a control group(201 patients)and an involvement group(51 patients)based on presence or absence of lung involvement.The data on clinical characteristics and features of chest high-resolution CT(HRCT)in the modeling group was collected.Univariate analysis was performed among the groups to determine the relevant factors affecting lung involvement in pSS patients.Binary logistic regression analysis was performed on related factors to screen independent risk factors.A prediction model was established based on the independent risk factors.A verification and value analysis of the column-line prediction model were completed through data collection of the verification group.Results Age,disease course,cough,Raynaud's phenomenon,C-reactive protein(CRP),anti-SSA antibody,and HRCT were the relevant factors affecting lung involvement in pSS patients(all P＜0.05).Further binary logistic regression analysis showed that old age,prolonged disease course,cough and abnormal HRCT imaging were independent risk factors for lung involvement in SS patients(all P＜0.05).A nomogram risk prediction model was constructed based on independent factors.The model verification results indicated that the calibration chart showed better performance in the prediction model.The AUC of the area under the receiver operating characteristic(ROC)curve was 0.993 the modeling group and 0.995 in the validation group.Conclusions The clinical characteristics and the results of chest CT are closely related with lung involvement in patients with pSS.Old age,prolonged disease course,cough,and abnormal HRCT imaging are independent risk factors affecting lung involvement in patients with pSS.The prediction model established on this basis has a higher predictive value for the occurrence of lung involvement in patients receiving after-loading radiotherapy.

Objective:To explore the feasibility of long board detector of digital radiography(DR)in clinical application.Methods:The long board detector(detector)was erected and placed upright.The scale long ruler with marked metal lead wire was placed at 20 cm in front of the center of long axis of the board of detector,which paralleled medial axis.Three test cards of spatial resolution were respectively placed at three positions(upper,middle and lower)of detector,and they were stuck on the board of detector as 30cm intervals between each other and 45° position.The exposures were conducted at 100,150,and 200 cm of source image distance(SID).The incident doses were tested,which obtained from different SID spots of upper,middle and lower positions of detector.The spatial resolutions of 3 positions were determined through observed the images of cards.The ratio of the marked scale length with metal lead wire to actual length of lead wire was measured through the projection of the scale length,so as to obtain the amplification rate of different spot positions.The spatial distribution of effective focal plane on the direction of long axis of detector,and the morphological change of that were observed.Results:When SID spots were respectively 100,150 and 200cm,the amplification rates of images decreased with increasing SID.The difference of amplification rates among three SID spots was significant(F=223.80,P<0.001).There was significant difference in the corresponding radiation doses among different SID spots(F=7.57,P<0.05).The spatial resolution was constantly 1.8 LP/mm.There was heel effect along with the direction of short axis of detector.The effective focal spot on the direction of long axis of detector appeared up-down symmetrical display.Conclusion:The long board detector of DR equipment has realized the capture for the images of the overall length of spine or the overall length of lower limbs in one exposure,which can meet the clinical requirement,and improve the detection efficiency of X-ray.

Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P＜0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P＜0.05,P＜0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.

Objective:The effect of intermedin (IMD) on ATP-induced activation of inflammatory bodies and pyroptosis of cells and its mechanism were studied using lipopolysaccharide (LPS)-sensitized mouse macrophage line RAW 264.7.Methods:The cells were divided into the control groups, the LPS groups, LPS+IMD groups, and LPS+IMD+LY294002 groups. The expression of interleukin (IL)-1β and IL-18 and the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory cells were detected by real-time PCR and western blotting, and the pyroptosis of cells was detected by propidium iodide (PI) staining. The measurement data was represented by MS± SD, and the inter-group difference was compared with ANOVA calculations, and P<0.05 represented the difference with statistical significance. Results:Compared with the control group [(0.83±0.09) vs (0.49±0.04)], the ratio of phosphorylated phosphatidylinositol-3-kinase, p-PI3K)/phosphatidylinositol-3-kinase (PI3K) (0.44±0.05) and p-Akt/Akt (0.27±0.06) in the LPS group was significantly decreased. The ratios of p-PI3K/PI3K (1.22±0.18) and pAkt/Akt (0.83±0.09) in LPS+IMD group was significantly increased ( F=31.40, P<0.001; F=50.88, P<0.001). Compared with the control group, the mRNA and protein expressions of IL-1β, IL-18 and NLRP3 inflammasome (NLRP3, caspase-1, ASC) in RAW264.7 cells were up-regulated in the LPS group (LPS and ATP). Compared with LPS group, IMD treatment inhibited the expression of inflammatory cytokines IL-1β, IL-18 and NLRP3 inflammasome, which was blocked by LY294002, a blocker of PI3K/Akt pathway. The results of real-time PCR showed that the relative expression of IL-1β mRNA was (1.00±0.11) in the control group, (8.32±0.61) in the LPS group, (8.32±0.55) in the LPS+IMD group, and (7.23±0.41) in the LPS+IMD+LY group ( F=15.42, P<0.001). The relative expression of IL-18 mRNA in the control group was (1.00±0.17), (1.82±0.21) in the LPS group, (1.14±0.15) in the LPS+IMD group, and (1.53±0.11) in the LPS+IMD+LY group respectively ( F=18.16, P<0.001). The relative expression of NLRP3 mRNA in the control group was (1.00±0.13), (2.58±0.18) in the LPS group, (1.07±0.17) in the LPS+IMD group, and (1.33±0.32) in the LPS+IMD+LY group respectively ( F=15.98, P< 0.001); The relative expression of caspase-1 mRNA in the control group was (1.00±0.09), (6.20±0.19) in the LPS group, (3.43±0.06) in the LPS+IMD group, and (5.50±0.45) in the LPS+IMD+LY group respectively ( F=18.39, P<0.001). The relative expression of ASC mRNA in the control group was (1.00±0.21), (4.58±0.48) in the LPS group, (2.07±0.51) in the LPS+IMD group, and (3.33±0.32) in the LPS+IMD+LY group respectively ( F=15.19, P<0.001). Western blotting results showed that the relative expression of IL-1β protein was as follows: (100%) in the control group, [(188±14)%] in the LPS group, [(112±11)%] in the LPS+IMD group, and [(171±27)%] in the LPS+IMD+LY group respectively ( F=21.25, P<0.001). The relative expression of IL-18 protein in the control group was 100%, [(183±16)%] in the LPS group, [(115±19)%] in the LPS+IMD group, and [(179±23)%] in the LPS+IMD+LY group respectively ( F=19.62, P<0.001). The relative expression of NLRP3 protein was 100% in the control group, [(149±15)%] in the LPS group, [(106±10)%] in the LPS+IMD group, and [(144±15)%] in LPS+IMD+LY group respectively ( F=14.35, P<0.001). The relative expression of ASC protein was 100% in the control group, [(188±12)%] in the LPS group, [(110±18)%] in the LPS+IMD group, and [(192±8)%] in the LPS+IMD+LY group ( F=15.79, P<0.001). Conclusion:IMD inhibits the activation of NLRP3 inflammasome and cell pyroptosis by regulating PI3K/Akt activity.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive activity and are morphologically similar to conventional monocytes and granulocytes. The development and classification of these cells have, however, been controversial. The activation network of MDSCs is relatively complex, and their mechanism of action is poorly understood, creating an avenue for further research. In recent years, MDSCs have been found to play an important role in immune regulation and in effectively inhibiting the activity of effector lymphocytes.Under certain conditions, particularly in the case of tissue damage or inflammation, MDSCs play a leading role in the immune response of the central nervous system. In cancer, however, this can lead to tumor immune evasion and the development of related diseases. Under cancerous conditions, tumors often alter bone marrow formation, thus affecting progenitor cell differentiation, and ultimately, MDSC accumulation. MDSCs are important contributors to tumor progression and play a key role in promoting tumor growth and metastasis, and even reduce the efficacy of immunotherapy. Currently, a number of studies have demonstrated that MDSCs play a key regulatory role in many clinical diseases. In light of these studies, this review discusses the origin of MDSCs, the mechanisms underlying their activation, their role in a variety of clinical diseases, and their function in immune response regulation.

Objective:To study the use of preS1-tp fusion protein as a novel vector to mediate the entry of small interfering RNA (siRNA) targeting the carboxy-terminal nuclear localization signal (NLS) region of hepatitis B virus (HBV) core protein into HBV-infected hepatocytes, and to further explore the HBV replication inhibition and covalently closed circular DNA synthesis.Methods:HepG2.2.15 cells expressing the human sodium taurocholate co-transporting polypeptide were established on the basis of lentivirus infection system. siRNA against HBV NLS region was designed and synthesized. PreS1-tp fusion protein expression and purification was observed to test its ability to cell entry and DNA binding. NLS siRNA were delivered into HepG2.2.15- sodium taurocholate co-transporting polypeptide cells by preS1-tp fusion protein as a vector to observe the effects of NLS siRNA on HBV replication and covalently closed circular DNA levels. Analysis of variance was used for comparison between multiple groups, and the measurement data differences between groups were analyzed by t-test.Results:HepG2.2.15-sodium taurocholate co-transporting polypeptide cell line was successfully constructed. Screened synthetic HBV NLS siRNA had significantly inhibited HBV replication. The preS1-tp fusion protein was expressed and purified on a large-scale. The fusion protein as a vector for HBV NLS siRNA had targeted delivery. The result showed that the fusion protein had effectively targeted siRNA to Hepg2.2.15-sodium taurocholate co-transporting polypeptide cell, which not only had effectively inhibited the expression of HBV mRNA, HBsAg and HBeAg, but also had significantly reduced the levels of HBV DNA and covalently closed circular DNA.Conclusion:The preS1-tp fusion protein constructed in this study uses the dual functional characteristics of preS1 binding to hepatocyte HBV receptor, and tp binding to nucleic acids, and targets HBV NLS siRNA against HBV-infected cells and block rcDNA from being transported to nucleus. siRNA plays a role in inhibiting HBV replication and covalently close circular DNA synthesis, providing a new strategy for the treatment of chronic hepatitis B caused by HBV infection, and a new research perspective for the complete elimination of HBV from the body.

Objective:To retrospectively analyze the blood leukocytes (WBC), lymphocytes (LYM), lymphocyte% (LYM%), and serum total immunoglobulin (IGA, IGG, IGM) and complement (C3, C4) index levels to explore its predictive value for the outcome of COVID-19 severe pneumonia.Methods:Eighty-five COVID-19 patients with severe pneumonia diagnosed in our hospital were randomly selected and were divided into good outcome group (50 cases) and poor outcome group (35 cases). WBC, LYM, LYM%, IGA, IGG, IGM, and C3, C4 level data, and analyze the differences between the two groups, the correlation of each indicator, and ROC curves of single and joint detection to explore relationship between indicators and outcomes, and the predictive efficacy of indicators on outcomes.Results:Differences in WBC, LYM, LYM%, IGG, and IGA levels were significant between the two groups ( P=0.000, 0.015, 0.000, 0.000, 0.001), among them with significant differences, LYM and LYM% were significantly positively correlated ( r=0.669, P=0.000), while WBC and LYM% levels were significantly negatively correlated ( r=-0.600, P=0.000), WBC and IGA levels were significantly positively correlated ( r=0.283, P=0.009) and IGG and IGA levels were also significantly positively correlated ( r=0.0.442, P=0.000); After logistic regression analysis, WBC, LYM, LYM%, IGG, and IGA are all important influencing factors ( P=0.001, 0.022, 0.000, 0.000, 0.003); but only the levels of WBC, IGG, and LYM% are Independent risk factors ( P=0.034, 0.004, 0.001), the ROC curve of the single detection and joint detection of their predicted outcome performance, respectively, and the max AUC (AUC=0.890, P=0.000) at the time of joint testing of WBC, LYM% and IGG, index YI=0.657, it has the greatest predictive power for adverse outcomes, with a sensitivity of 77.10% and a specificity of 88.00%. IGM, C3, C4, IGG/IGM, and C3/C4 levels were not significantly different( P=0.066, 0.204, 0.076, 0.310, 0.156). Conclusions:The levels of WBC, LYM, LYM%, IGG, and IGA in the early admission of COVID-19 infected patients with severe pneumonia have important predictive value for the outcome of them. WBC, LYM% and IGG levels are independent risks and joint detection of the three indexes have the best predictive performance.

Botulinum toxin type A was firstly used to treat two patients with familial benign pemphigus, who showed poor response to conventional therapies. Case 1, a 64-year-old male patient, presented with erythema and erosions on bilateral axillary and inguinal regions for 2 years, and was injected with botulinum toxin type A at a dose of 50 U in the right axillary fossa and right groin separately. Case 2, a 33-year-old female patient, presented with erythema and blisters on bilateral axillary and inguinal regions and the right waist for 9 years, and was injected with botulinum toxin type A at a dose of 25 U in the left axillary fossa, right waist and bilateral groins separately. After the injection of botulinum toxin type A, sweating was inhibited in the 2 patients within 1 week, and skin lesions were gradually attenuated within 2 weeks. One month after the injection, erythema and erosions on bilateral axillary and inguinal regions mostly regressed in the case 1, and no recurrence was observed during 18-month follow-up. Six weeks after the injection, most of the skin lesions regressed in the case 2, only patchy hyperpigmentation was observed, and no obvious new lesions occurred. A few lesions recurred in the case 2 during 10-month follow-up, but were attenuated after the treatment with topical glucocorticoids.

Objective:To evaluate the effect of danshensu on proliferation and apoptosis of M5-stimulated HaCaT cells (a psoriasis-like cell model) , and to explore its relationship with Yes-associated protein (YAP) expression.Methods:HaCaT cells were stimulated with M5, a mixture containing 10 μg/L interleukin (IL) -1α, IL-17, IL-22, tumor necrosis factor (TNF) -α and oncostatin M, for 48 hours to establish a psoriasis-like cell model. Then, the cell model was divided into several groups to be treated with 0 (control group) , 0.125, 0.25 and 0.5 mmol/L danshensu respectively, and HaCaT cells receiving no treatment served as the blank control group. Real-time quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of YAP respectively in these groups; methyl thiazolyl tetrazolium (MTT) assay was conducted to estimate the cellular proliferative activity after 24-, 48- and 72-hour treatment with danshensu, flow cytometry to evaluate the effect of danshensu on cell cycle and apoptosis, and Western blot analysis to determine expression of cell cycle-related proteins (cyclin A, cyclin B1, cyclin D, cyclin E) and apoptosis-related proteins (cleaved caspase-3, Bcl-2, BAX, p53 and p21) . One-way analysis of variance was used for comparing means in several groups, and least significant difference (LSD) - t test for multiple comparisons. Results:The mRNA and protein expression of YAP significantly differed among the blank control group, control group, 0.125-, 0.25- and 0.5-mmol/L danshensu groups (both P < 0.001) , so did the cellular proliferative activity at 24, 48 and 72 hours (all P < 0.001) . The 0.125-, 0.25- and 0.5-mmol/L danshensu groups all showed significantly decreased mRNA and protein expression of YAP (mRNA: 1.76 ± 0.04, 1.54 ± 0.05, 1.33 ± 0.05 respectively; protein: 1.78 ± 0.06, 1.49 ± 0.32, 1.27 ± 0.04 respectively) , and cellular proliferative activity at 48 hours (1.66 ± 0.04, 1.52 ± 0.02, 1.34 ± 0.04 respectively) compared with the control group (mRNA: 2.04 ± 0.04; protein: 2.10 ± 0.06; cellular proliferative activity: 1.82 ± 0.03; all P < 0.05) . Flow cytometry showed significant differences in the proportions of cells at G0/G1, S and G2/M phases as well as in the apoptosis rates among the above 5 groups (all P < 0.001) . Compared with the control group, the 0.125-, 0.25- and 0.5-mmol/L danshensu groups showed significantly higher proportions of cells at G0/G1 and G2/M phases, but lower proportions of cells at S phase (all P < 0.05) . Additionally, the apoptosis rates were significantly higher in the 0.25- and 0.5-mmol/L danshensu groups than in the control group (both P < 0.05) . Western blot analysis revealed significant differences in the expression of cell cycle-related proteins and apoptosis-related proteins among the above 5 groups (all P < 0.001) . Conclusion:Danshensu can inhibit the proliferation of the psoriasis-like cell model and promote its apoptosis, likely by suppressing YAP expression.