Objective:To analyze the expression of heat shock protein 90α (HSP90α) in pancreatic cancer tissues and its potential diagnostic value for pancreatic cancer.Methods:A retrospective study was conducted on surgical specimens and clinical data from 99 patients with pancreatic cancer who were treated at Qingdao Municipal Hospital from January 2018 to May 2023, including 58 males and 41 females, with the age of (63.5±23.5) years. Among them, 44 patients (44.4%) were used for pathological examination and prognostic analysis, while 55 patients (55.6%) were tested for plasma HSP90α levels to evaluate its diagnostic efficacy for pancreatic cancer. Blood samples from 119 healthy individuals undergoing routine physical examinations at the same hospital during the same period were collected, including 74 males and 45 females, with the age of (50.5±25.5) years, and plasma HSP90α levels were measured. Immunohistochemistry (IHC) was performed to detect the expression of HSP90α in cancerous and adjacent non-cancerous tissues. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of HSP90α, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125) for pancreatic cancer. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival rates. The correlation between HSP90α positive expression in cancer tissues and mutant p53 positive expression was analyzed using Spearman correlation analysis.Results:Immunohistochemical analysis showed that the positive expression rate of HSP90α in pancreatic cancer tissues was 81.8%(36/44), higher than that in adjacent non-cancerous tissues 13.6%(6/44)( χ2=19.82, P<0.01). HSP90α positive expression in pancreatic cancer tissues was positively correlated with mutant p53 positive expression (correlation coefficient was 0.57, P<0.001). The median plasma HSP90α level in the pancreatic cancer group ( n=55) was 83.30 (48.30, 212.00) μg/L, which was significantly higher than that in the normal control group ( n=119), with a median of 37.00 (29.20, 43.50) μg/L, showing a statistically significant difference ( Z=-7.34, P<0.001). The area under the ROC curve (AUC) for plasma HSP90α in diagnosing pancreatic cancer was 0.85 (95% CI: 0.77-0.92), with an optimal cutoff value of 53.52 μg/L, yielding a sensitivity of 69.1% (38/55) and a specificity of 98.3% (117/119). The AUC for HSP90α in diagnosing pancreatic cancer was higher than that of CEA, CA19-9, and CA125. In the immunohistochemical analysis of cancer tissues, the one-year cumulative survival rate of the HSP90α-negative group ( n=8) was 87.5%, which was significantly higher than that of the HSP90α-positive group ( n=36), which was 18.8%( χ2=12.74, P<0.001). Conclusions:HSP90α is highly expressed in pancreatic cancer tissues, which is positively correlated with mutant p53 positive expression. Patients with positive HSP90α expression have a poorer prognosis. HSP90α demonstrates good diagnostic performance for pancreatic cancer and holds potential for clinical application.

Stiff-person syndrome （SPS） is a rare autoimmune neurological disorder with atypical symptoms and signs，which often leads to missed diagnosis or misdiagnosis，resulting in delayed treatment. This article reports a female patient，aged 72 years，who was diagnosed with SPS，and her symptoms were improved after symptomatic treatment including intravenous injection of human immunoglobulin，corticosteroids，clonazepam，and baclofen. It is suggested that early diagnosis and timely treatment can improve the quality of life and prognosis of SPS patients with positive anti-amphiphysin antibodies.

Objective:To analyze the expression of heat shock protein 90α (HSP90α) in pancreatic cancer tissues and its potential diagnostic value for pancreatic cancer.Methods:A retrospective study was conducted on surgical specimens and clinical data from 99 patients with pancreatic cancer who were treated at Qingdao Municipal Hospital from January 2018 to May 2023, including 58 males and 41 females, with the age of (63.5±23.5) years. Among them, 44 patients (44.4%) were used for pathological examination and prognostic analysis, while 55 patients (55.6%) were tested for plasma HSP90α levels to evaluate its diagnostic efficacy for pancreatic cancer. Blood samples from 119 healthy individuals undergoing routine physical examinations at the same hospital during the same period were collected, including 74 males and 45 females, with the age of (50.5±25.5) years, and plasma HSP90α levels were measured. Immunohistochemistry (IHC) was performed to detect the expression of HSP90α in cancerous and adjacent non-cancerous tissues. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of HSP90α, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125) for pancreatic cancer. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was used to compare survival rates. The correlation between HSP90α positive expression in cancer tissues and mutant p53 positive expression was analyzed using Spearman correlation analysis.Results:Immunohistochemical analysis showed that the positive expression rate of HSP90α in pancreatic cancer tissues was 81.8%(36/44), higher than that in adjacent non-cancerous tissues 13.6%(6/44)( χ2=19.82, P<0.01). HSP90α positive expression in pancreatic cancer tissues was positively correlated with mutant p53 positive expression (correlation coefficient was 0.57, P<0.001). The median plasma HSP90α level in the pancreatic cancer group ( n=55) was 83.30 (48.30, 212.00) μg/L, which was significantly higher than that in the normal control group ( n=119), with a median of 37.00 (29.20, 43.50) μg/L, showing a statistically significant difference ( Z=-7.34, P<0.001). The area under the ROC curve (AUC) for plasma HSP90α in diagnosing pancreatic cancer was 0.85 (95% CI: 0.77-0.92), with an optimal cutoff value of 53.52 μg/L, yielding a sensitivity of 69.1% (38/55) and a specificity of 98.3% (117/119). The AUC for HSP90α in diagnosing pancreatic cancer was higher than that of CEA, CA19-9, and CA125. In the immunohistochemical analysis of cancer tissues, the one-year cumulative survival rate of the HSP90α-negative group ( n=8) was 87.5%, which was significantly higher than that of the HSP90α-positive group ( n=36), which was 18.8%( χ2=12.74, P<0.001). Conclusions:HSP90α is highly expressed in pancreatic cancer tissues, which is positively correlated with mutant p53 positive expression. Patients with positive HSP90α expression have a poorer prognosis. HSP90α demonstrates good diagnostic performance for pancreatic cancer and holds potential for clinical application.

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

ObjectiveIn order to explore the utilization value of the seeds dropped in the harvesting， processing， storage and transportation of Prunellae Spica， the character， turgidity and chemical composition of the seeds were analyzed and compared with those of the commercially available varieties， such as chia seeds and basil seeds. MethodCharacter was observed directly. The turgidity was determined according to the method of general rule 2101 of Chinese Pharmacopoeia （part Ⅳ， the 2020 edition）. The contents of six phenolic acids （danshensu， protocatechuic acid， protocatechuic aldehyde， caffeic acid， salviaflaside and rosmarinic acid） were determined by ultra performance liquid chromatography （UPLC）， acetonitrile （A）-0.1% formic acid aqueous solution （B） was used as mobile phase for gradient elution （0-7 min， 2%-8%A； 7-13 min， 8%A； 13-14 min， 8%-17%A； 14-30 min， 17%A）， the detection wavelength was at 280 nm. The liposoluble components were extracted by n-hexane and identified by gas chromatography-mass spectrometry （GC-MS）， and the contents of five fatty acids， namely palmitic acid， oleic acid， stearic acid， linolic acid and α-linolenic acid， were determined on a DB-35MS capillary column （0.25 mm×60.0 m， 0.25 µm）， the injection temperature was 250 ℃， the carrier gas was high-purity helium with a flow rate of 1.0 mL·min^-1 and the splitting ratio of 50∶1. The volatile oil was extracted by steam distillation method and its components were identified by GC-MS on a WM-5MS capillary column （0.25 mm×30.0 m， 0.25 µm） with the injection temperature of 250 ℃， the flow rate of 1.0 mL·min^-1 and the splitting ratio of 10∶1. ResultPrunellae Spica seeds were slightly smaller than chia seeds and basil seeds， and their color of seed coat was obviously different. Prunellae Spica seeds had strong water absorption and swelling characteristics， and the turgidity was 17.4 mL·g^-1， which was lower than that of chia seeds （25.2 mL·g^-1） and basil seeds （35.6 mL·g^-1）. Prunellae Spica seeds were rich in phenolic and fatty acids， while the content of volatile oil was very low. The main phenolic acids were salviaflaside and rosmarinic acid， with the contents of 0.579% and 0.392%， respectively. The total content of five fatty acids in n-hexane extract was 90.1%， and total content of unsaturated fatty acids was 80.6%， among which content of α-linolenic acid was 50.0%， which was slightly lower than 57.2% of chia seeds and similar to 50.0% of basil seeds. ConclusionPrunellae Spica seeds have good turgidity， rich in phenolic acids and unsaturated fatty acids， and especially with high amount of α-linolenic acid. It is worthy of being developed as functional food to realize comprehensive utilization of the waste resources of Prunellae Spica.

Vestibular migraine and patent foramen ovale are closely related conditions with linked incidence rates.This systematic review presents the potential pathophysiological mechanisms underlying the association of patent foramen ovale with vestibular migraine，delves into the clinical features and classifications of vestibular migraine as well as the shunt status and anatomical features of patent foramen ovale，and also discusses the outcome of vestibular migraine following a patent foramen ovale closure.Vasoactive peptide，microemboli，inflammation，and genetic theories have been proposed for the association of the two conditions.Although most studies support a link between vestibular migraine and patent foramen ovale，evidence is lacking to prove that patients with vestibular migraine can gain significant benefits from a patent foramen ovale closure，and moreover，the surgery-related serious adverse events and risks，such as atrial fibrillation and new-onset headache，need careful consideration.

Background and Objectives: Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis. Methods: and Results: We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3. Conclusions We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.

Objective:To culture and identify dermal mesenchymal stem cells (DMSCs) in skin lesions of patients with psoriasis, and to determine the expression of hairy and enhancer of split-1 (HES1) and chemokine ligand 6 (CXCL6) in DMSCs.Methods:DMSCs were isolated from skin lesions of 15 patients with psoriasis and normal skin tissues of 18 healthy controls, and then subjected to culture. Cell phenotypes were identified by flow cytometry, and mRNA and protein expression of HES1 and CXCL6 was determined by real-time fluorescence-based quantitative PCR (RT-PCR) and Western blot analysis respectively. Comparisons were performed between 2 groups by using t test. Results:There was no difference in the morphology of DMSCs between the psoriasis group and control group. The mRNA expression of HES1 and CXCL6 in the psoriasis group was 3.56 and 3.44 times that in the control group respectively, and there was a significant difference between the two groups (both P < 0.05) . The protein expression of HES1 and CXCL6 in DMSCs was significantly higher in the psoriasis group than in the control group (both P < 0.05) . Conclusion:The high expression of HES1 and CXCL6 in DMSCs from lesions may be involved in the occurrence of psoriasis.

Background: Carbohydrate antigen 72-4 (CA72-4) is generally recognized as a tumor marker of digestive system. However, elevated serum CA72-4 level is also evident in many benign diseases and healthy subjects, and its sensitivity in diagnosing malignant tumor is quite poor. Aims: To reassess the value of CA72-4 in tumor screening and diagnosis. Methods: Three cohorts were established in this study. Inpatients who underwent a serum CA72-4 measurement and had a definite final diagnosis were included into Cohort 1 (retrospective study). Inpatients with elevated serum CA72-4 level who had not been diagnosed as malignant tumor before admission were included into Cohort 2 (retrospective study). Individuals who underwent a serum CA72-4 measurement and willing to take a follow-up for at least 2 years were included into Cohort 3 (prospective study). Malignancies had been preliminarily excluded in all individuals in Cohort 3 before enrollment. Results: Among the 2 173 patients recruited in Cohort 1, the prevalence of positive serum CA72-4 was significantly higher in patients with malignancies than those without (16.4% vs. 7.4%, P<0.05). The sensitivity and specificity of CA72-4 for diagnosis of malignant tumor were 36.5% and 76.2%, respectively, at the cut-off value (2.955 U/mL) identified by ROC curve analysis. Among the 1 807 patients recruited in Cohort 2, most of the participants (76.5%) did not have malignancies. Serum CA72-4 level was associated with the histological classification, tumor differentiation and TNM staging of malignancies (P<0.05). Among the 376 individuals who underwent a follow-up for no less than 2 years in Cohort 3, elevated serum CA72-4 level did not increase the risk of malignant tumor (OR=1.268, 95% CI: 0.283-5.687). Conclusions: CA72-4 is not a sensitive marker for tumor screening, its value as an item in physical examination should be re-evaluated. In patients who had positive serum CA72-4 and malignant tumor was ruled out in initial examination, the necessity of long-term follow-up of serum CA72-4 needs to be discussed.