Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Wolbachia infection and genotyping in Aedes albopictus / 上海预防医学

ObjectiveTo investigate the infection and genotypes of Wolbachia in Aedes albopictus. MethodsAdult and larval samples of Aedes albopictus were collected from different residential and wild areas from 2020 to 2021， Wolbachia surface protein （wsp） gene was amplified and genotyped for wAlbA and wAlbB by PCR， and sequenced for phylogenetic analysis. The difference of detection rate among different habitats， male and female adult mosquitoes， adult and larvae was compared by χ2 analysis. ResultsThe detection rate of Wolbachia in adult and larvae of Aedes albopictus were 43.5% （77/177） and 70.4% （190/270）， respectively， with a statistically significant difference （χ2=32.086，P<0.001）， and wAlbA and wAlbB were mainly detected together. The detection rate of Wolbachia in female and male Aedes albopictus were 50.7% （76/150） and 3.7% （1/27）， respectively， with a statistically significant difference（χ2=20.533，P<0.001）. The detection rate of adult Aedes albopictus in Songjiang wild area， residential area and Hongkou residential area were 91.7% （55/60）， 18.8% （22/117） and 41.7% （30/72）， respectively， with a statistically significant difference （χ2=54.322，P<0.001）. Genotyping and phylogenetic analysis showed that adult and larvae of Aedes albopictus infected with Wolbachia were mainly wAlb A and wAlb B. In addition， some sequences formed clades independently， and the genetic distance from other sequences was relatively large. ConclusionInfection of Wolbachia in Aedes albopictus is relatively common in Songjiang District. The main genotypes are wAlb A and wAlb B and there may be other subtypes， which are worthy of further exploration and research.

Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism / 中国天然药物

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Peptic ulcer bleeding in the elderly and analysis of its correlation with Helicobacter pylori infection / 公共卫生与预防医学

Objective To analyze the risk factors of bleeding in elderly patients with peptic ulcer disease (PUD) and its correlation with Helicobacter pylori (Hp) infection, and to provide a theoretical basis for clinical diagnosis and treatment of elderly patients with PUD bleeding. Methods A total of 418 elderly PUD patients admitted to our hospital from June 2019 to June 2020 were selected. The 13C-urea breath test was used to determine HP infection. PUD patients were divided into observation group (n=87, bleeding) and control group (n=331, no bleeding). Age, sex, ulcer number, ulcer location, ulcer stage, ulcer diameter and other clinical data were collected. Univariate analysis and logistic regression were used to analyze the risk factors of bleeding in elderly PUD patients. The Forrest classification was used to evaluate the severity of PUD bleeding patients. Pearson correlation analysis was performed between Forrest classification and Hp infection in elderly PUD bleeding patients. Results There were statistically significant differences between the two groups in the course of disease, PUD history, NSAIDs application/ulcer number, ulcer diameter, ulcer location, ulcer stage, Hp infection and NSAIDs application (P<0.05). Multivariate logistic regression analysis showed that the use of NSAIDs, active ulcer, Hp infection and ulcer diameter ≥2 cm were risk factors for bleeding in elderly patients with PUD (P<0.05). The Hp positive rate in Forrest I patients was significantly higher than that in Forrest II and Forrest III patients (P<0.05). The positive rate of Hp in Forrest II patients was significantly higher than that in Forrest III patients. Pearson correlation analysis showed that Hp infection was positively correlated with the severity of peptic ulcer bleeding in the elderly (r=0.512, P<0.05). Conclusion The risk of bleeding from PUD is higher in the elderly, especially in patients with active ulcer, Hp infection and ulcer diameter ≥ 2 cm. In the treatment process of PUD patients, the eradication therapy of Hp should be emphasized, which can reduce the risk of bleeding.

Knowledge graph analysis of pyroptosis research in traditional Chinese medicine based on VOSviewer and CiteSpace / 中国中药杂志

To explore the research hotspots and frontier directions of pyroptosis in the field of traditional Chinese medicine(TCM), the authors searched CNKI and Web of Science for literature related to pyroptosis in TCM, screened literature according to the search strategy and inclusion criteria, and analyzed the publication trend of the included literature. VOSviewer was used to draw author cooperation and keyword co-occurrence network diagrams, and CiteSpace was employed for keyword clustering, emergence, and timeline view. Finally, 507 Chinese literature and 464 English literature were included, and it was found that the number of Chinese and English literature was increasing rapidly year by year. The co-occurrence of the authors showed that in terms of Chinese literature, there was a representative research team composed of DU Guan-hua, WANG Shou-bao and FANG Lian-hua, and for English literature, the representative research team was composed of XIAO Xiao-he, BAI Zhao-fang and XU Guang. The network visualization of Chinese and English keywords revealed that inflammation, apoptosis, oxidative stress, autophagy, organ damage, fibrosis, atherosclerosis, and ischemia-reperfusion injury were the primary research diseases and pathological processes in TCM; berberine, resveratrol, puerarin, na-ringenin, astragaloside Ⅳ, and baicalin were the representative active ingredients; NLRP3/caspase-1/GSDMD, TLR4/NF-κB/NLRP3, and p38/MAPK signaling pathways were the main research pathways. Keyword clustering, emergence, and timeline analysis indicated that the pyroptosis research in TCM focused on the mechanism of TCM monomers and compounds intervening in diseases and pathological processes. Pyroptosis is a research hotspot in the area of TCM, and the current discussion mainly focuses on the mechanism of the therapeutic effect of TCM.

Diagnosis and treatment of four cases of asymptomatic and non-hydrous ureteral calculi / 北京大学学报(医学版)

This paper analyzed the clinical data, diagnosis and treatment of 4 asymptomatic patients with ureteral calculi without hydrops in our hospital from October 2018 to January 2019, and comprehensively discussed the previous literature. The 4 patients in this group had no obvious clinical symptoms, no positive stones were found in the B-ultrasound of the urinary system, and no hydroureter and hydroureter of the affected side was found. Urinary CT scan confirmed ureteral stones. They were all located in the lower ureter, and the stones obstructed the lumen. The stones were round and smooth, and there was no obvious hyperplasia and edema in the surrounding mucosa. The lithotripsy was completed in the first-stage operation, and the DJ catheter was left behind for one month after the operation. Based on the clinical diagnosis and treatment process of the 4 cases of asymptomatic calculi in this group and the analysis of previous studies, these patients were mostly detected by imaging examinations or other systematic imaging examinations during the regular review of urinary calculi. Ureteral stones with obstruction did not necessarily have stone-related symptoms. The onset of renal colic involved an increase in intraluminal pressure, related stimulation of nerve endings, smooth muscle spasms caused by stretching of the ureteral wall, and systemic changes in cytokines and related hormones. Cascade reactions, etc., were associated with the movement of stones down. Ureteral stones without hydrops were mostly located in the lower ureter, which had a certain buffering effect on obstructive pressure. Asymptomatic ureteral calculi could also induce irreversible damage to renal function, and the proportion of damage increased with the diameter of the stone. Patients with a history of urinary calculi, especially those with asymptomatic stones for the first time, should be paid attention to during clinical follow-up. At present, there are few research reports on asymptomatic and non-accumulating ureteral calculi. We analyze the clinical diagnosis and treatment process and characteristics of this group of patients combined with previous literature to provide a reference for the diagnosis and treatment of such patients.

Research progress in gut-skin axis and its association with traditional Chinese medicine theory / 中国中药杂志

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.

Mechanism of ferroptosis in chronic heart failure based on theory of "harmful hyperactivity and responding inhibition" / 中国中药杂志

Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of "harmful hyperactivity and responding inhibition" is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to "inhibition and hyperactivity becoming harmful". The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should "nourish heart Qi, regulate the five Zang-organs, so as to restrain excess". The middle-stage treatment should "active blood, resolve phlegm, dispel pathogen, and eliminate turbidity", so as to alleviate hyperactivity. The late-stage treatment should "warm Yang, replenish Qi, active blood, and excrete water". Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.

Research progress in quality control of Bufonis Venenum in preparations / 中国中药杂志

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.

Clinical comprehensive evaluation of Xiangju Capsules in treatment of rhinosinusitis / 中国中药杂志

The articles involving Xiangju Capsules were retrieved, and qualitative research and quantitative research methods were combined to evaluate the evidence of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) of this drug. Multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Xiangju Capsules in the treatment of rhinosinusitis and clarify the precise clinical positioning. The dimensions are graded A, B, C, or D. Multi-source safety evidence showed that the main adverse reactions were gastrointestinal reactions, rash, itching, dizziness, and headache. Based on the available studies, the risk is controllable and the safety is grade A. Meta-analysis showed that Xiangju Capsules + conventional western medicine could recover the Lund-Kennedy score, Lund-Mackay score, and CT score, relieve headache, nasal congestion, olfactory disturbance, and facial pain, with the effectiveness is grade B. The incremental cost-effectiveness ratio of Xiangju Capsules + conventional western medicine compared with conventional western medicine alone in the treatment of chronic rhinosinusitis was 263.71 yuan, about 0.82% of the per capita disposable income. The results of sensitivity analysis showed that the research results were relatively robust. Based on the assumption that the per capita disposable income in 2020 will be the threshold of patients' willingness to pay, it is more economical to use Xiangju Capsules + conventional western medicine. The drug belongs to grade A of the national medical insurance, with an average daily cost of 3.06 yuan, and the economy is grade B. This formula is modified from classic formulas and characteristic empirical formulas, be capable of improving immunity and preventing repeated attacks. It can be used for acute and chronic rhinitis-rhinosinusitis. It had a wide range of applicability, especially for the patients with head and face tenderness. Service innovation was reflected in the measures to guarantee supply, capacity, scalability, and coverage of grass-roots sales channels. The industrial innovation was improved through the management of medicinal resources, pharmaceutical industry, production technology, quality control, scientific research and development, and this formula won three national invention patents. Comprehensively, the innovation of Xiangju Capsules is grade B. According to the survey of 188 medical practitioners and 196 patients in 20 provinces, municipalities, and autonomous regions of China, the drug was characterized by easy preparation and administration, individualized medication, simple technology and management, convenient use, storage, and transport, and controllable adverse reactions, with the suitability is grade B. Xiangju Capsules showed the cost of 45.9 and 275.4 yuan for treatment of acute and chronic rhinitis-rhinosinusitis, respectively, being well affordable. It was sold in 35 000 medical institutions in China. The dosage form was suitable for transportation, storage, and grass-root application. With rich, sustainable, and available medicinal resources, the accessibility of Xiangju Capsules is grade A. This drug can be used for both acute and chronic rhinitis-rhinosinusitis, clearing heat and expelling pus, and strengthening the exterior to prevent relapse. After this drug was available on the market, over 4 000 cases were studied, with rich experience in human use accumulated, and characteristics of traditional Chinese medicine is grade B. Overall, the clinical value of Xiangju Capsules is class B. It is suggested that Xiangju Capsules should be used in accordance with the relevant policies of basic clinical drug administration to play its role.

Comparison on blood-prostate barrier permeability of tanshinone extract and corresponding major monomers / 中国中药杂志

In this study, the transmittance of tanshinone Ⅱ_A(Tan Ⅱ_A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ_A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ_A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ_A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ_A in the extract at each time point were higher than those of the corresponding single active components(P<0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ_A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ_A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.

Research on dynamic on-line monitoring method of moisture attribute in three honey-processed Chinese herbal slice based on in-situ general model / 药学学报

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

Traditional Chinese Medicine Treats Hepatic Fibrosis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Hepatic fibrosis is a common complication of chronic liver disease， seriously affecting patients' quality of life and leading to severe consequences such as cirrhosis and liver cancer. Modern medicine has made progress in the treatment of hepatic fibrosis， while it still faces certain challenges and limitations. Therefore， seeking new therapeutic strategies is of great clinical significance. The nuclear factor-κB （NF-κB） signaling pathway plays a role in regulating inflammation and immune responses. Recent studies have shown that the NF-κB signaling pathway plays a key role in the occurrence and development of hepatic fibrosis. The abnormal activation of the NF-κB signaling pathway leads to the overexpression of genes related to liver inflammation and fibrosis， thereby promoting the development of hepatic fibrosis. Traditional Chinese medicine （TCM） is a traditional treatment method with unique advantages and potential. In recent years， increasing studies have proved that TCM can treat hepatic fibrosis by regulating the NF-κB signaling pathway. The active ingredients in Chinese herbal medicines can intervene in the activation of the NF-κB signaling pathway to inhibit inflammatory responses， thereby reducing the severity of hepatic fibrosis. This article reviews the mechanisms of TCM in treating hepatic fibrosis via the NF-κB signaling pathway and evaluates the efficacy and discusses the clinical application prospects of relevant Chinese herbs and formulae， aiming to provide references for further research and clinical practice.

Analysis of the ocular clinical features and pathogenic genes in patients with Alstr?m syndrome / 中华眼底病杂志

Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.

Mechanism of mesenchymal stem cell-derived exosome for alleviating hepatic ischemia-reperfusion injury / 中华器官移植杂志

The review focuses upon the mechanism of exosome derived from mesenchymal stem cells in hepatic ischemia-reperfusion injury(IRI)to provide references for clinical application of exosomes in alleviating hepatic IRI.

High-frequency ultrasonography-assisted evaluation of treatment outcomes of erysipelas: a prospective controlled study / 中华皮肤科杂志

Objective:To measure the skin thickness in patients with erysipelas by high-frequency ultrasonography (HF-USG), and to compare the clinical efficacy of systemic antibiotics alone versus their combination with glucocorticoids in the treatment of erysipelas.Methods:Hospitalized patients with erysipelas were enrolled from Zhongda Hospital, Southeast University from January to December in 2021, and randomly divided into the study group and control group according to the order of visits. The study group was treated with systemic cefathiamidine for 7 days followed by oral methylprednisolone at a dose of 0.4 mg·kg -1·d -1, while the control group was treated with cefathiamidine alone. Before and after the treatment for 10 days, the thicknesses of the epidermis-dermis layers and subcutaneous tissues were measured by HF-USG at the sites of the most severe skin lesions on the affected limbs and at the corresponding sites on the healthy limbs, and white blood cell (WBC) counts, neutrophil (NEU) counts, as well as C-reaction protein (CRP) levels were determined. The t test and non-parametric test were used to compare the efficacy between two groups. Results:A total of 23 patients with erysipelas were enrolled. Among the 12 patients in the study group, 8 were males and 4 were females, and their age was 71.4 ± 11.4 years. Among the 11 patients in the control group, 7 were males and 4 were females, and their age was 67.4 ± 11.1 years. Before treatment, the thicknesses of the epidermis-dermis layers (0.33 ± 0.12 cm) and subcutaneous tissues (1.08 ± 0.49 cm) in the study group were not significantly different from those in the control group (0.25 ± 0.09 cm, 0.98 ± 0.46 cm; t = -1.83, -0.49, P = 0.081, 0.626, respectively). After the 10-day treatment, the thicknesses of the epidermis-dermis layers and subcutaneous tissues of the skin lesions on the affected limbs significantly decreased in both groups compared with those before treatment (both P < 0.05), and the decrease in the thicknesses of subcutaneous tissues was significantly stronger in the study group (0.32 ± 0.33 cm) than in the control group (0.10 ± 0.07 cm; t = 2.20, P = 0.039). Before treatment, the WBC counts ([11.16 ± 4.42] × 10 9/L), NEU counts ([8.26 ± 4.16] × 10 9/L) and CRP levels (median [ Q1, Q3]: 72.20 [19.28, 140.50] mg/L) in the study group were not significantly different from those in the control group ([10.10 ± 4.53] × 10 9/L, [7.21 ± 3.00] × 10 9/L, 34.40 [8.00, 74.20] mg/L, respectively; t or Z = 0.60, 0.71, -0.85, P = 0.578, 0.496, 0.196, respectively). After the 10-day treatment, the WBC counts, NEU counts, and CRP levels significantly decreased in both groups compared with those before treatment (all P < 0.05) . Conclusion:The combined treatment with systemic antibiotics and glucocorticoids could effectively alleviate skin inflammation, and more rapidly reduce the thicknesses of inflamed subcutaneous tissues in patients with erysipelas compared with systemic antibiotics alone.

Relationship between preoperative serum albumin concentrations and postoperative delirium in patients undergoing total knee/hip arthroplasty / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.

Progress of lipoxygenase in liver ischemia reperfusion injury / 中华肝胆外科杂志

Liver ischemia reperfusion injury (IRI) is one of the main causes of liver dysfunction or functional failure after liver transplantation or liver resection. As the main organ of lipid metabolism, liver is closely related to lipid metabolic balance. Lipoxygenase is a non-heme iron-containing oxidases that oxidizes polyunsaturated fatty acids to produce hydroxy-eicosanotetraenoic acid. Lipoxygenase is excessively expressed during liver ischemia, causing lipid metabolic disorders. High expression of several proinflammatory cytokines induced by lipoxygenase during liver reperfusion. Lipid peroxidation induced by lipoxygenase leads to the production of lipid oxygen free radicals, which induces iron death mainly characterized by lipid peroxidation, thus affecting apoptosis and tissue damage. This review mainly introduces the latest progress of lipoxygenase in liver IRI.

Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.