A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To analyze the distribution pattern of TCM syndrome elements in elderly patients with sepsis and septic shock, as well as the relationship between TCM syndrome elements, Sepsis Sequential Organ Failure Score (SOFA), Acute Physiology and Chronic Health Score Ⅱ (APACHE Ⅱ), and short-term mortality prognosis.Methods:A retrospective analysis was conducted on the clinical data of 58 patients treated in the Emergency Department and ICU of Dongzhimen Hospital of Beijing University of Chinese Medicine and the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 1, 2021, to May 1, 2022. The patients were divided into a sepsis group of 38 cases and a septic shock group of 20 cases based on disease type. Basic information, TCM syndromes, SOFA score, and APACHE Ⅱ score of the two groups were collected. The survival and death statuses of the two groups within 28 days of admission were separately analyzed. Association rule analysis was used to investigate the distribution pattern of TCM syndromes in patients, and logistic regression analysis was performed to explore the relationship between TCM syndromes, SOFA score, APACHE Ⅱ score, and death prognosis.Results:In the sepsis group, the main TCM syndromes included yin deficiency, lung, phlegm, qi deficiency, blood stasis, heat, and yang deficiency; while in the septic shock group, the main TCM syndromes were yin deficiency, lung, yang deficiency, and qi deficiency. Multifactor logistic regression analysis showed that in the sepsis group, liver syndromes [ OR (95% CI)=0.080 (0.011, 0.578), P=0.012], meridians and collaterals [ OR (95% CI)=0.088 (0.011, 0.718), P=0.024], SOFA score [ OR (95% CI)=0.524 (0.310, 0.886), P=0.016], and APACHE Ⅱ score [ OR (95% CI)=0.426 (0.186, 0.977), P=0.044] were independent influencing factors for patient mortality prognosis. In the septic shock group, phlegm [ OR (95% CI)=0.014 (0.001, 0.267), P=0.005], meridians and collaterals [ OR (95% CI)=0.041 (0.003, 0.618), P=0.021], yang deficiency [ OR (95% CI)=0.028 (0.002, 0.427), P=0.010], SOFA score [ OR (95% CI)=0.543 (0.310, 0.950), P=0.032], and APACHE Ⅱ score [ OR (95% CI)=0.633 (0.408, 0.985), P=0.042] were independent influencing factors for patient mortality prognosis. Conclusions:The sepsis group mainly exhibits a mixture of deficiency and excess, while the septic shock group predominantly shows deficiency. Qi deficiency and yin deficiency are consistent throughout the disease progression. Meridians and collaterals, high SOFA score, and high APACHE Ⅱ score in elderly patients with sepsis and septic shock may indicate a poorer prognosis.

Per- and poly-fluoroalkyl substances (PFAS) are a new type of persistent organic pollutants that have received extensive attention in recent years. This article reviewed the population characteristics of environmental exposure to PFAS, as well as the potential health effects. Previous studies have verified that people are exposed to PFAS mainly through ingestion, and food and water are the dominant contributors. In terms of exposure characteristics, geographical, gender, age, and occupational differences have an impact on the level of PFAS exposure in the corresponding populations by influencing their behavioral characteristics and metabolic levels, with occupational exposure receiving more attention, especially in the exploration of novel PFAS. PFAS associate with a variety of adverse health effects caused by hepatorenal toxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and carcinogenicity. However, some of the conclusions are not completely consistent, and the published epidemiological studies have focused on children and young people, lacking relevant data of the elderly. Future research can pay more attention to the elderly population and carry out validation exploration on controversial conclusions.

OBJECTIVE: To investigate characteristics of silent alpha thalassemia genes in child-bearing adults in Guangdong, in order to provide data for the prevention and control of hemoglobin H disease. METHODS: A total of 8 752 cases were collected from January 2016 to December 2020. Gap-PCR was used to detect the deletional of α-thalassemia mutations (-α^3.7, -α^4.2), while PCR reverse dot blot hybridization assay (RDB) was used to detect the non-deletional α-thalassemia mutations (Hb CS, Hb QS and Hb Westmead). RESULTS: Among 8 752 subjects, 717 cases of silent α-thalassemia were detected, the detection rate was 8.19%, including 555 cases of deletional α-thalassemia (77.41%) and 162 cases of non-deletional α-thalassemia 22.59%. The mean corpuscular volume (MCV) of deletional silent α-thalassemia was (82.09±4.10) fl, and mean corpuscular hemoglobin (MCH) was (27.03±1.37) pg, which both were over the diagnostic cut-off value for thalassemia. The MCV of non-deletional silent α-thalassemia was (81.07±4.93) fl, and MCH was (26.77±2.20) pg. According to the diagnostic criteria, if using MCV<82 fl or (and) MCH<27 pg as a positive criteria for screening thalassemia in the childbearing age, the screening sensitivity was 53.14% and different in different genotype, among which αα^QS/αα was 100%, -α^3.7/αα, -α^4.2/αα, αα^CS/αα and αα^WS/αα was 62.15%, 63.41%, 44.83% and 39.62%, respectively. Namely, nearly half the carriers of such mutations might have escaped detection as a result of their screening strategy. CONCLUSION When a couple is preparing for pregnancy, if one of them has been determined to be mild α-thalassemia or hemoglobin H disease, other half is necessary to carry out silent α thalassemia detection to prevent the birth of children with hemoglobin H disease even if MCV>82 fl and MCH>27 pg.
Adult ; Pregnancy ; Female ; Humans ; alpha-Thalassemia/diagnosis* ; Genotype ; Mutation ; Erythrocyte Indices ; Polymerase Chain Reaction ; China ; beta-Thalassemia/genetics*

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

AIM:To investigate the neuroprotective effect of 17β-estradiol(E2)on retina light damage in BALB/c and C57BL/6 mice and provide experimental data for the successful construction of a research model for E2 against retinal light damage.METHODS:Totally 40～45 adult female BALB/c or C57BL/6 mice were divided into six groups, 6 for each group: normal control, ovariectomized control, ovariectomized light(mice were stimulated with continuous white light at 10000 lx for 4, 8, 12, 16, and 24h after 14d of ovariectomy), intravitreal administration sham operation, saline and E2 pre-treatment groups(2μL saline or 10-5mol/L E2 were intravitreal injected respectively after 14d of ovariectomy operation and 24h of dark adaptation). The morphological and functional changes of the retina were detected by paraffin section HE staining, TUNEL staining and electroretinogram.RESULTS:In the ovariectomized light group, the thickness of the inner/outer nuclear layer decreased significantly from the 4h stimulation of 10000 lx white light group. Intravitreal administration of E2 significantly inhibited the apoptosis of retinal cells in the two strains of mice(P<0.01)and the decrease of amplitudes of a- and b-waves in max-ERG of C57BL/6 mice(P<0.05).CONCLUSION:The light loss sensitivity of two strains of mice was different under the same light stimulation. E2 had a protective effect on both morphology and function of the retina in BALB/c mice, and had a significant protective effect on retina function in C57BL/6 mice.

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

OBJECTIVE: To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice. METHODS: Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation. RESULTS: Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine. CONCLUSION ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
Airway Remodeling ; Angiotensin-Converting Enzyme 2 ; Animals ; Methacholine Chloride ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ozone/adverse effects* ; Pneumonia

Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.