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.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

This paper summarizes professor ZHU Shengliang's academic idea and clinical experience in treating gastroesophageal reflux disease （GERD） with qi constraint and phlegm obstruction syndrome. It is believed that the core pathogenesis of GERD is the dysfunction of the liver， gallbladder， spleen and stomach， with binding of phlegm and stasis. The basic pathogenesis is the liver and gallbladder failing to dredge and disperse， the stomach failing to harmonize and descend， and the stomach qi counterflowing upward. In clinical practice， the treatment principle of regulating qi as the priority， resolving phlegm as the key， and activating blood as the assistant is applied， with harmonizing the stomach and directing counterflow downward throughout the whole process. A self-made Shugan Hewei Huatan Formula （疏肝和胃化痰方） is employed with the function of soothing the liver and rectifying qi， opening constraint and dissipating knot， dissolving phlegm and dispelling stasis， harmonizing stomach and directing counterflow downward， with an emphasis on flexible modification according to the syndrome as well as careful protection of stomach qi.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective:To identify the incidence and prevalence of inflammatory bowel disease (IBD) in the northern Chinese population of Jinan, Shangdong Province, along with its temporal trends from 2005 to 2022.Methods:By utilizing the data from the Jinan basic medical insurance system, a population-based IBD cohort was constructed. This facilitated the computation of both the incidence and prevalence rates of IBD, alongside their temporal trends throughout the 2005 to 2022 timeframe. The 95% confidence intervals were estimated using poisson regression.Results:The overall incidence rate of IBD showed a yearly increasing trend, with age-standardized incidence rates rising from 0.03/100 000 in 2005 to 5.39/100 000 in 2022. The age-standardized incidence rate of ulcerative colitis (UC) increased from 0.03/100 000 in 2005 to 4.97/100 000 in 2022. The age-standardized incidence rate of Crohn's disease (CD) rose from 0.05/100 000 in 2011 to 0.44/100 000 in 2022. The crude prevalence of IBD increased from 0.60/100 000 in 2005 to 32.39/100 000 in 2022. Specifically, the crude prevalence of UC increased from 0.60/100 000 in 2005 to 31.44/100 000 in 2022, while the crude prevalence of CD increased from 0.05/100 000 in 2011 to 1.19/100 000 in 2022.Conclusions:Analysis of recent medical insurance data reveals a continuous uptrend in both the incidence and prevalence of IBD in Jinan, a northern city in China. This underscores the urgent need for enhanced medical resources and healthcare guaruntee to ensure the well-being of individuals afflicted with IBD.

Objective To observe the effects of Baishile Capsules on neonatal neuronal activity and synaptic plasticity in hippocampus of depression model rats;To explore its mechanism of antidepressant.Methods Totally 32 SD rats were randomly divided into blank group,model group,fluoxetine group(5.4 mg/kg)and Baishile Capsules group(2.88 g/kg),with 8 rats in each group.The depression rat model was established by chronic unpredictable mild stress and single cage feeding,and drugs were administered at the same time as modeling for 21 consecutive days.Forced swimming test and open field test were used to evaluate the depressive-like behavior of rats,Golgi staining was used to observe the synaptic morphology of hippocampal neurons,and immunofluorescence was used to detect the positive expressions of BrdU/GABA-B,BrdU/c-fos,BrdU/GAP-43,BrdU/MAP-2 and CXCR4 in hippocampal tissue.Results Compared with the blank group,the immobility time of forced swimming experiment in the model group increased,and the horizontal and vertical time of open field experiment decreased significantly(P<0.01);the hippocampal neurons dendrites and dendritic spines atrophied,the density decreased,the branches became shorter,synaptic structure becomes blurred,and the longest and total lengths of synaptic branches significantly decreased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 proteins in hippocampal neonatal neurons decreased(P<0.05,P<0.01),and the expression of CXCR4 in hippocampal tissue decreased significantly(P<0.01).Compared with the model group,the immobility time of the forced swimming experiment in fluoxetine group and Baishile Capsules group significantly reduced,and the horizontal and vertical activity time of the open field experiment significantly increased(P<0.01);the number of dendritic spines in hippocampal neurons increased,synaptic damage improved,and the length of the longest and total branches of synapses significantly increased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 in hippocampal neonatal neurons significantly increased(P<0.05,P<0.01),and the positive expression of CXCR4 in hippocampal tissue significantly increased(P<0.01).Conclusion Baishile Capsules can regulate hippocampal synaptic plasticity and nerve regeneration by improving the activity and function of hippocampal neonatal neurons in depression model rats,exerting antidepressant effects.

Objective To investigate washing patterns in human simulated body fluids(SBF)by combining high doses of vancomycin,manuperenan and single compound with bone cement.The antibacterial effect of five common bacteria in orthopaedic infections were observed.Methods Vancomycin 2g and meropenem 3g were combined or alone mixed with ordinary bone cement 20g in aseptic operation.Six copies of antibiotic bone cement pellets were made,immersed in SBF,replaced with SBF buffer every 48 hours,sampled every 24 hours 2 μl drops in methicillin-resistant staphylococcus aureus(MRSA),petries of staphylococcus aureus,pseudomonas aeruginosa,E.coli,and extended-spectrum beta-lactamase(ESBL)-positive E.coli were observed for 24 hours and measured the size of the bactericidal rings of the washing fluid at each time point.The antibacterial effect of different ratios of antibiotic bone cement on 5 common orthopedic infections were compared.Results Compound antibiotic group had a better bactericidal effect,and the drug continues to be given for about 30 days.Wancomycin alone could not cover E.coli,ESBL positive E.coli,pseudomonas aeruginosa,and melopicillin alone had only a partial mild bactericidal effect on MRSA around 3 to 6 days after use.The effect on staphylococcus aureus and pseudomonas aeruginosa lasted only about 15 days.Conclusion The combined antibiotic bone cement has a more comprehensive,longer duration and better bactericidal effect than the alone antibiotic bone cement.

Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.