Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To construct time-series by adopting autoregressive integrated moving average(ARIMA)model for analyzing the trend and genotype characteristics of single-center human papillomavirus(HPV)infection in Tianjin area.Methods A total of 7 236 female patients who underwent HPV testing in a hospital from January 2018 to December 2022 were selected.HPV infection status and genotype distribution in Tianjin area from 2018 to 2022 were compared.ARIMA model time-series was constructed,and model fitting was analyzed.The number of HPV infections in 2023 was predicted and compared with the actual occurrence,the predictive performance of the model was evaluated.Results HPV infection rate in Tianjin area from 2018 to 2022 was 14.41％,with the highest rate(15.47％)in the age group of 31-40 years.Among the positive specimens,the proportion of single type HPV infection was the highest,accounting for 73.54％(767/1 043),with high-risk HPV being the main type.The highest infection rates of low-risk and high-risk types were type HPV-6(2.59％)and type HPV-16(16.06％),re-spectively.ARIMA model was constructed,and the optimal model was ARIMA(0,1,2)(0,1,1)12,with akaike in-formation criterion(AIC)and bayesian information criterion(BIC)values of 3.877 and 4.005,respectively.There was no statistical significance in Ljung-Box Q=8.828 showed by white noise test(P＞0.05).The number of HPV infection in 2023 was predicted by the model.The overall trend of the actual value and the predicted value was basi-cally consistent,RMSE,MAPE and MAE of the model were 6.289,34.149 and 4.706,respectively,suggesting that the model had a good prediction effect.Conclusion Among the female population in Tianjin area,HPV infec-tion is mainly caused by single,high-risk type,with HPV-16 having the highest infection rate.There is seasonal variation in HPV infection in Tianjin.ARIMA model has good prediction effect on the prevalence trend of HPV in-fection,which is suitable for short-term prediction.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective To explore the acute effects of NO₂ on children's respiratory hospitalization risk in Foshan City. Methods The daily average concentrations of six air pollutants such as NO2 and fine particulate matter, and meteorological data including average temperature and relative humidity in Foshan were collected from 2016 to 2019. Data on the daily number of children newly hospitalized for respiratory diseases (ECRH) in Foshan Women and Children Hospital were retrieved. Time series analysis was used to quantitatively evaluate the effect of daily NO2 concentration on the hospitalization risk of children with respiratory diseases. Results From 2016 to 2019, the average ECRH in the hospital was 10. The daily average concentrations of air pollutants NO₂, PM_2.5, PM₁₀, and SO₂ were 42.0 μg/m³, 35.3 μg/m³, 58.1 μg/m³, and 11.4 μg/m³, respectively. The air pressure, daily average temperature and relative humidity of atmosphere were 1008.4 Pa, 23.7℃ and 73.3%, respectively. ECRH was significantly correlated with the daily average concentration of NO2 (r=0.079, P<0.05). After excluding temperature, humidity and other influencing factors, for every 10 μg/m³ increase of NO2 concentration in the single pollutant model, the excess risk of ECHR in the hospital increased by 1.22% (95% CI: 0.06%, 2.40%) and 1.37% (95% CI: 0.23%, 2.53%) in lag0 and Lag1 day, respectively. The strongest effect appeared in lag0:7 with the excess risk increasing by 1.70% (95% CI:0.12%, 3.31%). In the NO₂ + SO₂ + CO + O₃_8h + PM_2.5 and NO₂ + SO₂ + CO + O₃_8h + PM₁₀ multi-pollutant models, significance correlation still existed between the daily average NO₂ concentration and ECHR in lag0, lag1 and lag0:1 to lag0:7. The strongest effect appeared in lag0:1, and the excess risks were 4.06% (95% CI: 1.83%, 6.34%) and 3.95% (95% CI: 1.85%, 6.09%), respectively. Dose-response relationship analysis showed a linear relationship between the daily average NO₂ concentration and ECHR, and the excess risk of new hospitalization gradually increased with the increase of daily average NO₂ concentration. Conclusion There was a significant correlation between NO₂ concentration and hospitalization risk of children with respiratory diseases in Foshan City, which suggests that the government should further strengthen the prevention and control of air pollution.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

ObjectiveTo explore the mechanism of Fangji Fulingtang in the treatment of acute kidney injury （AKI） induced by ischemia-reperfusion based on network pharmacology and experimental verification. MethodActive components of Fangji Fulingtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and previous report and targets of these components were predicted by SwissTargetPrediction. The targets of AKI were searched from GeneCards， Online Mendelian Inheritance in Man （OMIM）， the database of gene-disease associations （DisGeNET）， and Therapeutic Target Database （TTD）. Protein-protein interaction （PPI） network was constructed by STRING. Metascape was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of core targets. Cytoscape was employed to construct the "medicinal-active component-target-disease" network and “active component-target-pathway” network. AutoDock was applied for molecular docking. Finally， animal experiment was carried out to validate the mechanism of Fangji Fulingtang in treatment of AKI. ResultA total of 137 active components and 858 targets of Fangji Fulingtang， 1 294 targets of AKI， and 267 targets of Fangji Fulingtang in the treatment of AKI were screened out. Phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）， proto-oncogene tyrosine protein kinase （SRC）， protein kinase B1 （Akt1）， and mitogen-activated protein kinase 3 （MAPK3） were the key anti-AKI targets of Fangji Fulingtang， which were involved in 1 609 GO terms， particularly cell response to lipids， membrane rafts， and protein kinase activity， and 140 KEGG pathways such as PI3K/Akt signaling pathway， chemokine signaling pathway， and Toll-like receptor signaling pathway. Molecular docking showed that the core active components had strong binding affinity to the key targets. The hematoxylin and eosin （HE） staining results indicated that Fangji Fulingtang can significantly improve the pathological state and the serological results suggested that the levels of serum creatinine （SCr） and blood urea nitrogen （BUN） were significantly reduced. ConclusionThis study clarified the mechanism of Fangji Fulingtang in the treatment of AKI and found that Fangji Fulingtang had the multi-component， multi-target， and multi-pathway characteristics in the treatment of AKI. The result lays a foundation for further study of its specific mechanism.

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

Aim To determine the antiviral and anti-inflammatory effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency(4-1)against in vitro infection of SARS-CoV-2 and common coronaviruses.Methods The main chemical substances of 4-1 were analyzed by LC-MS.The toxicity and antiviral effects of of 4-1 were detected by MTT and by CPE assay, respectively.The viral loads in cell supernatant and the expression of inflammatory factors induced by viral infection were determined by qRT-PCR.Results The recommended prescription 4-1 contained 94 chemical compounds, including flavonoids, steroids, sesquiterpenoids, and so on.The range of selection indexes for SARS-CoV-2 and common coronaviruses was 8.44±0.4952.26±2.3.This prescription could inhibit the proliferation of SARS-CoV-2, the expression of ACE2 and S mRNA, and down regulate IL-1α and CCL-5/RANTES at 10, 5, and 2.5 g•L-1 doses.Further, at doses of 20, 10 and 5 g•L-1, it could inhibit the proliferation of three common coronaviruses and suppress the overexpression of IL-6, CXCL-8/IL-8, CXCL-10/IP-10, TNF-α, IFN-α, CCL-2/MCP-1, MIG and CCL-5/RANTES induced by OC43/229E infection.The inhibitory effects were dose-dependent.Conclusions The prescription 4-1 has antiviral and anti-inflammation effects against multiple coronaviruses.This study provides the research basis for the treatment of common respiratory viral infections and emerging infectious diseases such as COVID-19 by using traditional Chinese medicine.