ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo explore the distribution and evolution patterns of traditional Chinese medicine （TCM） syndromes and syndrome elements in psoriasis vulgaris （PV）. MethodsLiterature related to TCM syndromes of PV published in databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform （Wanfang）， VIP Chinese Technology Periodical Database （VIP）， Chinese Biomedical Literature Database （CBM）， PubMed， Embase， and Web of Science from their inception to December 31， 2023， was retrieved. Statistical analysis was conducted on the distribution of TCM syndromes and syndrome elements in the included studies. The data were further categorized into five-year periods to analyze the dynamic changes in syndromes and syndrome elements over time. ResultsA total of 2,853 studies were included， with 5,896 syndrome occurrences. The most common TCM syndromes in PV were blood-heat syndrome （2,167 occurrences， 36.75%）， blood-stasis syndrome （1,219 occurrences， 20.68%）， blood-dryness syndrome （1,124 occurrences， 19.06%）， and damp-heat syndrome （263 occurrences， 4.46%）. The most frequent syndrome categories included blood syndromes （4,680 occurrences， 79.38%） and dampness syndromes （347 occurrences， 5.89%）. The most common syndrome elements related to disease location were blood division （4,874 occurrences， 94.38%） and spleen （99 occurrences， 1.92%）. The most common syndrome elements related to disease nature were blood-heat （2,213 occurrences， 25.96%）， blood-dryness （1,434 occurrences， 16.82%）， and blood-stasis （1,330 occurrences， 15.60%）. Except for the period 1978-1983， blood-heat， blood-stasis， and blood-dryness syndromes consistently ranked among the top three， with their combined proportion showing an overall upward trend （from 67.65% to 81.69%）. The proportion of spleen deficiency with damp obstruction syndrome also increased （from 0.24% to 1.46%）. In terms of syndrome classification， the proportion of blood syndromes showed an overall upward trend （from 67.65% to 83.46%）， ranking first in all periods. The proportion of dampness syndromes showed a general downward trend （from 17.65% to 4.54%）， ranking second after blood syndromes in most periods except for 1994-1998 and 1999-2003. The proportion of spleen-related syndromes showed an overall increase （from 0.24% to 1.85%）. Regarding disease location elements， the proportion of blood division remained stable above 90%， while the proportion of spleen involvement increased （from 0.68% to 3.23%）. As for disease nature elements， blood-heat （from 19.23% to 33.27%） and blood-stasis （from 1.92% to 20.83%） significantly increased， while dampness initially decreased and then slightly increased （from 11.54% to 5.73%）. ConclusionIn the distribution of PV-related TCM syndromes， blood-heat， blood-stasis， and blood-dryness syndromes are the most common. Blood syndromes dominate syndrome classification， with disease location primarily in the blood division and disease nature characterized by blood-heat， blood-stasis， and blood-dryness. Evolutionary trends indicate that blood-heat， blood-stasis， and blood-dryness syndromes remain predominant and are increasing in proportion， while spleen deficiency with damp obstruction syndrome is also rising. Among syndrome classifications， the proportion of blood syndromes is increasing， dampness syndromes are decreasing， and spleen-related syndromes are on the rise. In terms of syndrome elements， blood division remains dominant， while spleen involvement is increasing. The proportion of blood-heat and blood-stasis is significantly increasing， while dampness first declines and then slightly rebounds. Overall， the mainstream TCM perspective of treating PV based on blood differentiation remains unchanged， with syndrome distribution focusing on blood division. The increasing importance of spleen deficiency and dampness in disease pathogenesis represents a new trend.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.

Objective:To explore the locations of the lumbosacral nerve roots by use of the magnetic stimulation.Methods:Thirty healthy subjects were studied. The projections of the right L 2 to S 1 intervertebral foramina on their body surfaces were determined manually with ultrasound assistance. Magnetic stimulation was applied to different nerve root segments to induce compound muscle action potentials (CMAP) in the vastus medialis, tibialis anterior, and gastrocnemius muscles of the lower limbs. The changes in latency, amplitude, and motor threshold were observed. Results:Magnetic stimulation on the L 2-L 3 segment resulted in a significant direct excitation of the vastus medialis. That on the L 5-S 1 segment evoked a significant direct excitatory effect on the tibialis anterior and gastrocnemius, with a motor threshold below 40%, an amplitude exceeding 1mV, and many effective responses. However, during the magnetic stimulation on the L 4 segment, the amplitude of the vastus medialis was above 1mV, with no significant differences in the number of effective responses among the muscle groups. Moreover, there was a stepwise change in the latency of effective muscle responses to magnetic stimulation at different segments. The CMAP latencies of 12+ ms for the tibialis anterior and 13+ ms for the gastrocnemius indicated activation of the L 5 and L 4 nerve roots, respectively, while those of 6+ ms, 7+ ms, and 8+ ms for the vastus medialis suggested activation of the L 4, L 3, and L 2 nerve roots, respectively. Conclusions:Based on the responses (CMAP latency, amplitude and motor threshold) of the vastus medialis, tibialis anterior and gastrocnemius to magnetic stimulation at different L 2 to S 1 segments, the spinal nerve root segments responsible for innervation can be inferred.

Objective This study summarized the clinical data of IBD patients receiving upadacitinib treatment in our hospital,and provided more Chinese data to better guide the treatment of upadacitinib in Chinese IBD population.Methods Clinical data of 11 patients with IBD who received upadacitinib treatment at Anhui Provincial Hospital from March 1,2023 to September 8,2024 were retrospectively analyzed.Platelet count,ESR,CRP,disease severity score,endoscopic score,and adverse reactions were compared before treatment,at the 4th and 8th week of treatment,and clinical response rate,clinical response rate,endoscopic response rate,and endoscopic response rate were calculated.SPSS 25.0 software was used for statistical analysis.Results The platelets,ESR and CRP of patients at the 4th and 8th week after upadacitinib treatment were decreased compared with those before treatment,with statistical significance.At the 4th week,the clinical response rate was 72.72％(8/11),the clinical remission rate was 0,the clinical response rate of UC patients was 83.33％(5/6),and the clinical response rate of CD patients was 60％(3/5).At the 8th week of treatment,the clinical response rate was 100％(10/10),the clinical remission rate was 80.00％(8/10),the clinical response rate of UC patients was 100％(6/6),the clinical remission rate of UC patients was 83.33％(5/6),the clinical response rate of CD patients was 100％(4/4),and the clinical remission rate of CD was 75％(3/4).There were no adverse reactions during treatment.Three patients were re-examined by colonoscopy,all of whom were severe UC patients and achieved mucosal healing.Conclusion Upadacitinib can rapidly,effectively and sustainably control the disease in patients with moderate and severe IBD,with high safety.

Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992％,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.

Objective:To investigate the correlation between serum proprotein convertase subtilisin/Kexin type 9 (PCSK9) level and white matter hyperintensities (WMHs) in healthy population.Methods:Consecutive healthy individuals underwent routine physical examinations at the Department of Neurology, Jinling Hospital Affiliated to Medical School of Nanjing University (April 2023 to December 2023) and Hexi Branch of Nanjing First Hospital (March 2024 to April 2024) were included prospectively. Enzyme-linked immunosorbent assay was used to detect serum PCSK9 level. The Fazekas scale was used to assess the severity of WMHs (total score 0-6) and they were divided into no or mild WMHs group (0-2) and moderate to severe WMHs group (3-6). Multivariate logistic regression analysis was used to determine the independent correlation between the serum PCSK9 level and the severity of WMHs. Results:A total of 177 subjects were enrolled, including 110 males (62.1%), aged 66.7±10.1 years. The median serum PCSK9 level was 203.9 ng/L. According to the Fazekas score, there were 102 patients (51.6%) in the no or mild WMHs group, and 75 (42.4%) in the moderate to severe WMHs group. One way analysis of variance showed that serum PCSK9 level significantly increased with the increase of WMHs total score ( P=0.001). The serum PCSK9 level in the moderate to severe WMHs group was significantly higher than that in the no or mild WMHs group (437.2±260.4 ng/L vs. 217.9±141.7 ng/L; P=0.001). Multivariate logistic regression analysis showed that after adjusting for age, gender, and other confounding factors, there was a significant independent correlation between higher serum PCSK9 level and moderate to severe WMHs (odds ratio 3.201, 95% confidence interval 2.107-5.082; P=0.001). Conclusion:Higher serum PCSK9 level is an independent risk factor for moderate to severe WMHs in healthy individuals.

To analyze the clinical features and genetic variants of a child with type 4 familial partial lipodystrophy (FPLD4) and the initial manifestation of diabetes.The male patient with the age of 13 years and 5 months, and the diabetes course was about 3 years, the patient was admitted to Children′s Hospital of Soochow University on November 10, 2021(4 th hospitalization at the hospital), in the course of diabetes, the children repeatedly suffered from diabetes ketoacidosis, and lipid metabolism complications gradually emerged.The gene sequencing showed that the proband and his mother carried dual gene mutations of PLIN1 c. 1325delG(p.G442Afs*99) and SPINK1 c. 194+ 2T>C(p.? ). The PLIN1 gene was the causal gene of FPLD4.The mutations of c. 1325delG in the PLIN1 gene had not been previously reported.Based on the clinical phenotype, family history and genetic testing findings, the patient was diagnosed as FPLD4.In addition, the mutation of SPINK1 c. 194+ 2T>C(p.? ) might increase the risk of chronic pancreatitis.This case report enriched the clinical characteristics and genotype data of FPLD4.Gene sequencing assisted the accurate diagnosis of the type of diabetes.The effects of dual gene mutations on disease progression should be concerned, which were of great significance to develop treatment regimen and disease management.