ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

Dyskinesia-hyperpyrexia syndrome（DHS）is an acute hyperpyrexia syndrome that is different from Parkinsonism-hyperpyrexia syndrome and serotonin syndrome in patients with advanced Parkinson's disease（PD），with the main symptoms of high fever，disturbance of consciousness，elevated creatine kinase，and dyskinesia. Syndrome of inappropriate secretion of antidiuretic hormone（SIADH）is a clinical syndrome caused by excessive secretion of antidiuretic hormone，which leads to the symptoms of dilutional hyponatremia，water retention，and increases in urine sodium and urine osmotic pressure. DHS has not received widespread attention in clinical practice，and there are rare reports of DHS comorbid with SIADH. This article reports the diagnosis and treatment processes of a case of DHS comorbid with SIADH and reviews the relevant literature，in order to guide the diagnosis and treatment of PD-related critical diseases.
Hyponatremia

Objective:To investigate the effect of continuous renal replacement therapy (CRRT) on energy metabolism and thermal balance in ICU patients with acute kidney injury (AKI).Methods:This study was a prospective observational study, which included AKI patients who underwent CRRT in ICU of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from May 2020 to December 2023. The patients' general clinical characteristics, comorbidities, body temperature, disease severity score, CRRT treatment time and filter lifespan were recorded. The concentrations of glucose and lactate in blood and ultrafiltrate, and the citrate level in the ultrafiltrate when regional citrate anticoagulation adopted were analyzed regularly. Subgroup analysis was carried out according to different anticoagulation modes and whether the patients with diabetes or shock. The changes of energy metabolism and thermal balance corresponding to the changes in glucose, lactate, citrate and body temperature induced by CRRT were calculated daily.Results:This study included 420 AKI patients undergoing CRRT. When the blood lactate was between 14-18 mmol/L, there was a loss of approximately 200-250 kcal of energy per day, while the blood lactate was between 6.5-11.5 mmol/L, the daily corresponding energy loss was about 100-150 kcal. During CRRT on the first day, the patients with diabetes or shock had a mild decrease of blood glucose, while patients without diabetes and shock had mild increase of blood glucose. When the target of blood glucose was gradually achieved, the mean daily increase of energy corresponding to blood glucose intake was about 100-130 kcal in patients undergoing CRRT. The mean daily increase of energy corresponding to citrate intake was approximately 330 kcal, when the patient was undertaken by CRRT with regional citrate anticoagulation. For every 1℃ decrease in body temperature, the mean daily heat loss caused by extracorporeal thermal radiation during CRRT was about 200 kcal.Conclusions:When conducting nutritional assessment and prescription for AKI patients supported by CRRT in the ICU, it is essential to fully consider the impact of CRRT on the patient's energy metabolism and heat balance. This includes the clearance of lactate, the balance of blood glucose, the intake of citrate, and the reduction in body temperature. Additionally, the type and stage of the disease, as well as individual differences, must be taken into account to achieve personalized nutritional assessment and precise implementation.

Vacuum compression molding (VCM) is a novel technology supporting the research and development of pharmaceutical solid dispersions. It is widely applied due to its precision and convenience in sample preparation. This technology integrates the principles of heating, melting, cooling, and vacuum compression to transform solid powders into shaped solids directly. By selecting different molds, temperatures, and pressures, researchers can prepare samples with diverse characteristics. This paper presents an overview of the equipment composition and working principles of VCM technology, demonstrating its distinct advantages in the formulation screening process of amorphous solid dispersions through comparative analysis with hot melt extrusion using case studies, and introduces its applications in the development of drug delivery systems and rheological characterization analysis, with a perspective on the future development of its functions.

Objective:To investigate the expression of chondroitin sulfate proteoglycan 4 pseudogene 12(CSPG4P12)in the small cell lung cancer(SCLC)tissue,its relationship with immune infiltration,and its effect on cell biological functions,and to clarify its effect in the occurrence and development of SCLC.Methods:The E-GEOD-60052 cohort was obtained by searching the ArrayExpress database for SCLC.The R language Bioconductor package was used to complete data filtering standardization,and 63 samples of SCLC tumor tissues and 7 samples of normal tissues were obtained.The Mann-Whitney U test was used to analyze the difference in CSPG4P12 expression levels between two groups.Pearson correlation analysis was used to evaluate the associations between CSPG4P12 expression levels and 47 immune checkpoint genes.The ESTIMATE algorithm and CIBERSORT algorithm were used to evaluate the correlations between CSPG4P12 expression and tumor immune cell infiltration.A case-control study was used to analyze the clinical data.A total of 230 patients with SCLC were selected as case group,and 230 healthy subjects were selected as control group.The genotyping of CSPG4P12 rs2880765,rs6496932 and rs8040855 was performed using TaqMan-MGB fluorescent probe labeling method.Odds ratio(OR)and 95％confidence interval(CI)were calculated by unconditional Logistic regression model to analyze the association between polymorphic genetic variation of CSPG4P12 gene and the risk of SCLC.The SCLC DMS114 cells were transfected with pUC-57 plasmid(control group)and CSPG4P12 over-expression plasmid(OV-CSPG4P12 group),respectively.The efficiencies of CSPG4P12 over-expression in two groups were verified by real-time fluorescence quantitative PCR(RT-qPCR)method.Cell counting kit-8(CCK-8)method was used to detect the cell proliferation activities of cells in two groups.Transwell chamber assay was used to detect the numbers of migration and invasion cells in two groups,respectively.Hoechst 33342 fluorescence staining was used to observe the cell apoptosis in two groups.Results:The ArrayExpress database E-GEOD-60052 cohort analysis showed that the expression level of CSPG4P12 mRNA in SCLC tissue was decreased compared with normal tissue(P＜0.001).The expression of CSPG4P12 had positive correlations with the immune checkpoint genes including leukocyte associated immunoglobulin like receptor 1(LAIR1)(r=0.47,P＜0.001),tumor necrosis factor(TNF)receptor superfamily member 9(TNFRSF9)(r=0.38,P＜0.01),and TNF superfamily member 9(TNFSF9)(r=0.44,P＜0.001).The ESTIMATE algorithm results showed that the matrix score,immune score and ESTIMATE composite score of the patients in CSPG4P12 low expression group were lower than those in CSPG4P12 high expression group(P＜0.01).The CIBERSORT algorithm results showed that compared with CSPG4P12 high expression group,the infiltration of M0 macrophages in CSPG4P12 low expression group was increased(P＜0.05)and the infiltration of mast cells resting was decreased(P＜0.05).The CSPG4P12 expression level had positive correlations with infiltration of mast cells resting(r=0.35,P=0.03)and mononuclear cell infiltration(r=0.34,P=0.034).In case-control studies,compared with AA genotype,CSPG4P12 rs2880765 AT and TT genotype carriers had a higher risk of SCLC(OR=1.68,95％CI=1.15-2.45,P＜0.01).The stratified analysis showed that genetic variation of rs2880765 A＞T increased the risk of SCLC in the male,younger age group(≤60 years)and smoking subgroups(males:OR=1.86,95％CI=1.18-2.93,P＜0.01;≤60 years:OR=1.73,95％CI=1.11-2.68,P＜0.01;smoking:OR=2.76,95％CI=1.49-5.13,P=0.001).The cell biology experiment showed that compared with control group,the proliferation abilities of the cells in OV-CSPG4P12 group were significantly decreased at 48 and 72 h(P＜0.01),while the number of migration cells at 24 h was significantly decreased(P＜0.01),the number of apoptotic cells at 24 h was increased(P＜0.05)and the number of invasion cells at 48 h was significantly decreased(P＜0.01).Conclusion:CSPG4P12 is lowly expressed in SCLC tumor tissue,which is associated with immune infiltration.The genetic variation of CSPG4P12 rs2880765 A＞T can increase the risk of SCLC,and its over-expression can inhibit cell proliferation,migration and invasion,and promote apoptosis.

Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

Objective:To observe the clinical efficacy of combined acupuncture and medication therapy in treating cerebral infarction in the acute stage and its impact on cerebral blood flow.Methods:A total of 160 patients with cerebral infarction were divided into 4 groups using the random number table method,with 40 cases in each group.Conventional treatment was given to all groups.Besides,the Chinese medication group received Tong Shen Fu Nao Wan;the acupuncture group received Xing Nao Kai Qiao(mind-refreshing and orifice-opening)needling therapy;the acupuncture-medication group received both Tong Shen Fu Nao Wan and Xing Nao Kai Qiao needling therapy.After 4 weeks of treatment,the clinical efficacy was assessed,and changes in the traditional Chinese medicine(TCM)symptom score and hemodynamics were compared among the four groups,as well as complications and adverse reactions.Results:After treatment,the acupuncture-medication group had a higher total effective rate compared to the other three groups(P<0.05).After the intervention,the National Institutes of Health stroke scale(NIHSS)score dropped in all groups(P<0.05)and was lower in the acupuncture-medication group than in the other three groups(P<0.05);all groups showed a decrease in the TCM symptom score(P<0.05),and the acupuncture-medication group was significantly lower than the other groups(P<0.05).After treatment,the blood flow velocity of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),and posterior cerebral artery(PCA)increased in every group(P<0.05),and the acupuncture-medication group had higher blood flow velocities compared to the other three groups(P<0.05).The acupuncture-medication group had the fewest number of complications among the four groups(P<0.05),and there was no statistical significance when comparing the adverse reactions among the groups(P>0.05).Conclusion:Compared to the separate use,the combined use of acupuncture and medication enhances the clinical efficacy,accelerates cerebral blood circulation,and boosts the recovery in treating cerebral infarction.

Objective:To observe the clinical efficacy of combined acupuncture and medication therapy in treating cerebral infarction in the acute stage and its impact on cerebral blood flow.Methods:A total of 160 patients with cerebral infarction were divided into 4 groups using the random number table method,with 40 cases in each group.Conventional treatment was given to all groups.Besides,the Chinese medication group received Tong Shen Fu Nao Wan;the acupuncture group received Xing Nao Kai Qiao(mind-refreshing and orifice-opening)needling therapy;the acupuncture-medication group received both Tong Shen Fu Nao Wan and Xing Nao Kai Qiao needling therapy.After 4 weeks of treatment,the clinical efficacy was assessed,and changes in the traditional Chinese medicine(TCM)symptom score and hemodynamics were compared among the four groups,as well as complications and adverse reactions.Results:After treatment,the acupuncture-medication group had a higher total effective rate compared to the other three groups(P<0.05).After the intervention,the National Institutes of Health stroke scale(NIHSS)score dropped in all groups(P<0.05)and was lower in the acupuncture-medication group than in the other three groups(P<0.05);all groups showed a decrease in the TCM symptom score(P<0.05),and the acupuncture-medication group was significantly lower than the other groups(P<0.05).After treatment,the blood flow velocity of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),and posterior cerebral artery(PCA)increased in every group(P<0.05),and the acupuncture-medication group had higher blood flow velocities compared to the other three groups(P<0.05).The acupuncture-medication group had the fewest number of complications among the four groups(P<0.05),and there was no statistical significance when comparing the adverse reactions among the groups(P>0.05).Conclusion:Compared to the separate use,the combined use of acupuncture and medication enhances the clinical efficacy,accelerates cerebral blood circulation,and boosts the recovery in treating cerebral infarction.

Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.

ObjectiveTo explore the typical behavior characteristics of children with autism in symbolic play and the value of Symbolic Play Test (SPT) in the early identification of autism. MethodsFrom November, 2021 to September, 2022, a total of 260 children with language problems were collected from Department of Children's Health Care of Binzhou Medical University Hospital. A total of 193 children with autism were as observation group and 67 normal children were as control group. All children played symbolic games. The typical behavioral characteristics of children with autism in SPT were explored, and a reliability and validity analysis based on the results of SPT was conducted. They were assessed with the adaptive and personal social scores of Gesell Development Scale, and the correlation of the scores of Gesell Development Scale and the score of SPT was analyzed. ResultsThe Cronbach's α coefficient of SPT of children with autism was 0.835 to 0.935, and the total score of SPT, the scores of surrogate object, fictional attribute and fictional object were positively correlated with each other (r > 0.607, P < 0.001). The SPT scores decreased in the observation group (t > 9.615, P < 0.001), and SPT score positively correlated with adaptability and personal-social development quotient (r > 0.609, P < 0.001). ConclusionTypical behavior of children with autism can be reflected in symbolic play, and SPT can provide clues for early identification of autism.