Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective To develop and validate a deep learning model based on chest CT images to accurately distinguish between drug-resistant(DR-TB)and-sensitive tuberculosis(DS-TB).Methods A retrospective study was conducted on 722 cases of confirmed secondary tuberculosis admitted in our center from January 2019 to December 2022.According to the results of antimicrobial susceptibility test,they were divided into 357 DS-TB cases and 365 DR-TB cases.Pre-existing U-Net segmentation model was employed to segment the lung parenchyma regions in CT images.The dataset was randomly partitioned into a training set and a testing set in an 8:2 ratio.Six 3D deep learning architectures(3D Swin Transformer,3D ShuffleNet v2,3D ViT,3D MobileNet v2,3D DenseNet,and 3D ResNet18)were employed to evaluate the discriminative efficiency between DS-TB and DR-TB.Hyperparameters were optimized by five-fold cross-validation on the training set to construct the optimal model.The performance of the constructed model was assessed using area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and F1-score.Six radiologists independently evaluated DR-TB identification on the test set,and their performance was compared with the best-performing deep learning model.Results The AUC value in DR-TB prediction was 0.583,0.704,0.698,0.758,0.736,and 0.841,respectively,for 3D Swin Transformer,3D ShuffleNet v2,3D ViT,3D MobileNet v2,3D DenseNet,and 3D ResNet18.The 3D ResNet18 model demonstrated optimal performance,achieving a sensitivity of 0.935(95%CI:0.880～0.987),a specificity of 0.642(95%CI:0.492～0.757),a PPV of 0.750(95%CI:0.663～0.835),an NPV of 0.896(95%CI:0.809～0.976),an AUC value of 0.841,and a F1-score of 0.832.The radiologists got a F1-score of 0.571,0.450,0.675,0.623,0.617 and 0.635,respectively,and the F1-score of the 3D ResNet18 model is all higher than that of the radiologists.The highest-performing radiologist achieved sensitivity,specificity,PPV and NPV of 0.701(95%CI:0.605～0.802),0.567(95%CI:0.447～0.684),0.651(95%CI:0.549～0.757),and 0.623(95%CI:0.500～0.754),with all these values lower than those of the 3D ResNet18 model(P<0.05).Class activation mapping showed that the 3D ResNet18 model could focus on key lesion areas.The class activation mapping demonstrated that the 3D ResNet18 model could effectively focus on critical lesion regions.Conclusion Our 3D ResNet18 model shows the best predictive performance in identifying DR-TB,and is expected to assist clinical diagnosis for DR-TB.

Porcine parvovirus(PPV)is a causative agent of porcine parvovirus infection(PPI),which significantly impacts the pig industry due to its association with reproductive dysfunction.The condition is characterized by stillbirth,mummified fetuses,fetal weakness,and abortion in pregnant sows.The pathogenic mechanism remains incompletely understood,with no effective therapeutic drugs available currently.Despite extensive research on the host's response to PPV in-fection and identification of various signaling pathway transduction mechanisms,a comprehensive understanding is still lacking.This review aims to summarize the current knowledge regarding al-terations in related signaling pathways following PPV infection,provide novel insights into the pathogenesis of PPV and facilitate the drug development.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.

Objective To explore the value of combined detection of cerebrospinal fluid lactate (LA), interleukin-27 (IL-27) and interferon-γ (IFN-γ) in diagnosing bacterial meningitis after neurosurgical operation in Intensive Care Unit (ICU). Methods A total of 54 patients with bacterial meningitis after neurosurgical operation in ICU were collected as disease group, and 62 patients without bacterial meningitis after operation were collected as control group. Fully automated biochemical analyzer and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of LA, IL-27 and IFN-γ in cerebrospinal fluid; the Logistic regression model was used to analyze the related factors affecting bacterial meningitis after operation; the receiver operating characteristic (ROC) curve was used to analyze the diagnostic values of LA, IL-27 and IFN-γ in cerebrospinal fluid for bacterial meningitis after operation. Results The glucose level in the disease group was significantly lower than that in the control group, while the white blood cell count and protein level were significantly higher than those in the control group (P < 0.01). The expression levels of LA and IL-27 in the cerebrospinal fluid in the disease group were significantly higher than those in the control group, while IFN-γ level in the cerebrospinal fluid was significantly lower than that in the control group (P < 0.01). Logistic regression analysis showed that LA, IL-27 and IFN-γ in the cerebrospinal fluid were the influencing factors of bacterial meningitis after neurosurgical operation in ICU (P < 0.05). The area under the curve (AUC) of LA combined with IL-27 and IFN-γ in cerebrospinal fluid in the diagnosis of bacterial meningitis after neurosurgical operation in ICU was 0.955, which was better than that of single diagnosis based on LA (AUC=0.806, Z=4.029, P < 0.001), IL-27 (AUC=0.858, Z=2.513, P=0.012) and IFN-γ (AUC=0.815, Z=3.680, P < 0.001) in cerebrospinal fluid, and the sensitivity and specificity of the combined diagnosis were 87.04% and 93.55% respectively. Conclusion The expression levels of LA and IL-27 in the cerebrospinal fluid of patients with bacterial meningitis after neurosurgical operation in ICU increase significantly, while the expression level of IFN-γ in the cerebrospinal fluid is significantly lower. The combined detection of three indicators has higher diagnostic value for postoperative bacterial meningitis compared with single detection.

OBJECTIVE To prepare progesterone-2-chloro-4-nitroaniline cocrystal （CNA） so as to improve the solubility of progesterone and primarily evaluate the safety of the progesterone cocrystal in vivo. METHODS Using progesterone as the main body and CNA as the ligand， progesterone-CNA cocrystal was prepared with solvent evaporation method. The cocrystal was characterized by X-ray single crystal diffraction， X-ray powder diffraction （XRPD）， differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy （IR）. The dissolution rate of cocrystal was compared with those of progesterone and physical mixture. Forty-eight female KM mice were randomly divided into normal group （phosphate buffer containing 0.1% dimethyl sulfoxide）， progesterone group （16 mg/kg）， CNA group （9 mg/kg）， progesterone-CNA cocrystal low-dose， medium- dose and high-dose groups （6， 12.5， 25 mg/kg）， with 8 mice in each group. They were given relevant medicine/solvent intramuscularly， once a day， for consecutive 14 d. The safety of cocrystal was evaluated primarily by determining/observing the changes in body weight， organ index， tissue morphology， blood routine indicators， and liver and kidney function indicators. RESULTS The new crystal structure in the X-ray single crystal diffraction results， the new characteristic peak in the XRPD pattern， the change of melting point in the DSC results， and the change of the characteristic peak position in the range of 3 500- 2 750 cm－1 and 1 700-1 250 cm－1 in the infrared spectrum all Δ 基金项目国家重点研发计划项目（No.2022YFC3502100） indicated that progesterone-CNA cocrystal was successfully ＊第一作者 硕士研究生 。研究方向 ：药物制备技术与工艺 。 prepared， and the dissolution rate of cocrystal was more than E-mail：SWB_1221@163.com # 通信作者教授，硕士生导师，博士。研究方向：药物制备技术与 twice that of the progesterone raw material drug. The results of 工艺。E-mail：wuxx-415@126.com in vivo safety experiments showed that the mortality rate of all 中国药房 2023年第34卷第13期 China Pharmacy 2023 Vol. 34 No. 13 · 1567 · groups was zero. Compared with normal group， uterine indexes of mice in progesterone group and progesterone-CNA cocrystal groups were significantly increased （P＞0.05）， and endometrium was also thickened； there was no statistical difference in the changes of body mass， liver and kidney function， liver index， kidney index， the number of leukocyte， lymphocyte and neutrophil in routine blood test among those groups （P＞0.05）， and the morphology of liver and kidney tissue has also no significant difference. However， the number of plasma red blood cells in the progesterone group decreased significantly （P＜0.05）， and there was no statistical significance in the number difference of red blood cells among progesterone-CNA cocrystal groups （P＞0.05）. CONCLUSIONS The progesterone-CNA cocrystal is successfully prepared with good safety in vivo， which significantly improve the solubility of progesterone.

ObjectiveTo explore the clinical efficacy of Huanglian Jiedutang as an adjunctive treatment for acute cerebral infarction complicated with gastric motility disorder. MethodSixty patients with acute cerebral infarction complicated with gastric motility disorder with fire toxin syndrome were randomly divided into a western medicine control group （control group） and a traditional Chinese medicine （TCM） combined treatment group （observation group）， with 30 cases in each group. The control group received basic treatment for cerebral infarction and relevant western medical symptomatic treatment based on the patients' gastrointestinal symptoms. The observation group received Huanglian Jiedutang in addition to the treatment provided to the control group. The treatment course was 7 days. Neurological deficit scores and gastrointestinal dysfunction scores were assessed in both groups before treatment and on the 4^th and 7^th days of treatment. Gastrointestinal electrographic parameters， serum citrulline （CIT）， and motilin （MTL） levels were measured in both groups before treatment and on the 7^th day of treatment. Clinical efficacy was compared between the two groups. ResultCompared with the baseline in both groups， the neurological deficit scores and gastrointestinal dysfunction scores were significantly reduced on the 4th and 7^th days of treatment （P<0.05）. The reductions in these scores were more significant on the 7^th day compared with those on the 4^th day of treatment （P<0.05）. On the 4^th and 7^th days of treatment， the observation group showed a significantly greater reduction in neurological deficit scores and gastrointestinal dysfunction scores compared with the control group （P<0.05）. On the 7th day of treatment， compared with the baseline， both groups showed a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. On the 7th day of treatment， compared with the control group， the observation group had a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. After 7 days of treatment， the total effective rate in the observation group was 90.00% （27/30）， higher than 76.67% （23/30） in the control group， but the difference was not statistically significant. ConclusionAdjunctive treatment with Huanglian Jiedutang can effectively improve the symptoms of neurological function impairment and gastrointestinal dysfunction in patients with acute cerebral infarction complicated with gastric motility disorder， increase gastric antral and gastric body electric wave amplitudes， improve gastric motility disorder， and increase serum CIT and MTL levels， thereby improving the imbalanced secretion function of the gastrointestinal tract.

Objective:To explore the value of 18F-FDG PET/CT combined with pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in diagnosis and differential diagnosis of stageⅠA small cell lung cancer (SCLC). Methods:From June 2017 to October 2021, 113 patients (75 males, 38 females; age 32-79 years) with stageⅠA lung cancer (70 with adenocarcinoma, 25 with squamous cell carcinoma, 18 with SCLC; patients with adenocarcinoma and squamous cell carcinoma were combined into non-SCLC (NSCLC) group) and 30 patients with benign pulmonary nodule (21 males, 9 females; age 37-77 years) from the Affiliated Qingdao Central Hospital of Qingdao University were retrospectively analyzed. All patients were examined by 18F-FDG PET/CT and serum tumor markers associated with lung cancer. Differences of the clinical, imaging and tumor markers data among different groups were analyzed by χ2 test, Fisher exact test and Kruskal-Wallis rank sum test. Independent risk factors were analyzed by logistic regression analysis and ROC curve analysis was used to analyze the value of different predictive factors in diagnosis and differential diagnosis of SCLC. Results:There were significant differences in SUV max, lobulation sign, spiculation sign, calcification, pleural traction sign, ProGRP, NSE and carcinoembryonic antigen (CEA) among SCLC, NSCLC and benign nodules groups ( H values: 14.06-20.54, χ2 values: 8.16-14.95, all P<0.05), in which lobulation sign of SCLC was more than that of benign nodules (12/18 vs 26.7%(8/30); χ2=7.41, P=0.007), spiculation sign (2/18 vs 51.6%(49/95); χ2=10.01, P=0.002) and pleural traction sign (1/18 vs 35.8%(34/95); χ2=6.47, P=0.011) were less than those of NSCLC, SUV max was higher than that of benign nodules (7.4(5.8, 9.0) vs 2.3(1.4, 5.1); H=51.82, P<0.001), ProGRP was higher than that of NSCLC and benign nodules (64.0(40.1, 84.8) vs 38.7(26.9, 47.6), 36.7(29.1, 40.5) ng/L; H values: 36.13, 43.96, P values: 0.002, 0.001) and NSE was higher than that of benign nodules (12.4(10.9, 14.5) vs 7.4(5.4, 11.8) μg/L; H=40.53, P=0.001). When differentiated SCLC from NSCLC, spiculation sign (odds ratio ( OR)=0.043, 95% CI: 0.004-0.450, P=0.009) and ProGRP ( OR=1.083, 95% CI: 1.035-1.133, P<0.001) were independent risk factors for SCLC, and the AUC of the two factors combination was 0.875, with the sensitivity and specificity of 14/18 and 84.2%(80/95). When differentiated SCLC from benign nodules, SUV max( OR=2.706, 95% CI: 1.099-6.662, P=0.030), ProGRP ( OR=1.165, 95% CI: 1.009-1.344, P=0.038) and NSE ( OR=1.639, 95% CI: 1.016-2.645, P=0.043) were independent risk factors for SCLC, and the AUC of the three factors combination was 0.985, with the sensitivity and specificity of 17/18 and 96.7%(29/30). Conclusion:18F-FDG PET/CT combined with tumor markers ProGRP and NSE is helpful to improve the diagnosis and differential diagnosis of stage ⅠA SCLC.

Objective To observe the value of 18F-FDG PET/CT combined with tumor markers for diagnosis of non stageⅠ A limited-stage small cell lung cancer(LS-SCLC).Methods Totally 87 cases of non stage Ⅰ A LS-SCLC(LS-SCLC group),137 of non stage Ⅰ A non-small cell lung cancer(NSCLC,NSCLC group)and 48 cases of pulmonary inflammatory lesions(inflammatory group)were enrolled.Patients'general data,tumor marker levels and PET/CT findings were comparatively analyzed.Logistic regression analysis was performed to evaluate the efficacy of parameters for diagnosing non stage Ⅰ A LS-SCLC.Results There were significant differences of patients'age,neuron-specific enolase(NSE),pro-gastrin-releasing peptide(ProGRP),carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCCA)and cytokeratin-19-fragment(CYFRA21-1),as well as of the maximum lesion diameter,maximum standard uptake value(SUVmax),morphology,spiculation sign,relationship between long axis and bronchus,lymph node fusion and proportion of lymph node with higher SUVmax than primary lesion among 3 groups(all P＜0.05).The area under the curve(AUC)of the combination of spiculation sign,NSE＞23.5 μg/L,ProGRP＞111.8 ng/L,SCCA≤2.5 μg/L and CYFRA21-1≤7.4 μg/L for differentiating LS-SCLC and NSCLC was 0.91,higher than that of each single parameter(all P＜0.05).AUC of the combination of SUVmax＞8.1,NSE＞19.4 μg/L,ProGRP＞72.5 ng/L and lymph node fusion for differentiating LS-SCLC and pulmonary inflammatory lesions was 0.99,higher than each single parameter(all P＜0.05).Conclusion 18F-FDG PET/CT combined with tumor markers ProGRP and NSE was helpful for diagnosing non stage ⅠA LS-SCLC.

Objective To investigate the protective effect of geniposide against diabetic rats with skin ulcer and the mechanism.Methods Rats were divided into a normal group,model group,and geniposide subgroups(Gen(L):200 mg/kg;Gen(H):500 mg/kg).Diabetic rats were treated with normal saline or geniposide by intragastric administration(n=6).Treatments were administered once a day,and the wound healing and inflammation of each group were recorded every day.After 7 days of treatment for diabetic skin ulcers,the wound area,tissue sections,TUNEL staining and Western blot were used to quantitatively analyze changes in wound healing,apoptosis,and related regulatory protein expression.Results Compared with the model group,the group receiving orally administered geniposide(200 and 500 mg/kg)showed significantly improved wound healing and increased contraction of the injured area.In terms of skin wound apoptosis in diabetic rats,TUNEL-positive cells were significantly reduced in geniposide subgroups(P<0.05).Geniposide significantly inhibited skin inflammation and promoted wound repair,which may be related to promotion of PI3K and Akt phosphorylation.Conclusions Geniposide promoted skin wound repair in diabetic rats by inhibiting inflammatory responses and apoptosis.