As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

Objective To explore the regulatory effect of long non-coding RNA HOX transcript anti-sense RNA(lnRNA HOTAIR)targeting tuberous sclerosis complex 1(TSC1)on podocyte injury in diabetic nephropathy(DN).Methods Mice podocyte MPC5 were divided into 6 groups:the control group,the high glucose group(the HG group),the HG+si-NC group,the HG+si-HOTAIR group,the HG+si-HOTAIR+sh-NC group,and the HG+si-HOTAIR+sh-TSC1 group.qPCR was used to detect the levels of lnRNA HO-TAIR and TSC1 mRNA.Cell viability was detected by cell counting kit-8(CCK-8),and apoptosis was detec-ted by flow cytometry.ELISA was used to detect the levels of inflammatory factors[IL-6,tumor necrosis fac-tor-α(TNF-α)]and the levels of oxidative stress indicators[reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)]were detected by corresponding reagent kit.Results Compared with the control group,the levels of lnRNA HOTAIR,apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG group were significantly increased(P<0.05),while the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Compared with the HG+si-NC group,the levels of lnRNA HOTAIR,ap-optosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR group significantly decreased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significant increased(P<0.05).Compared with the HG+si-HOTAIR+sh-NC group,the levels of apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR+sh-TSC1 group were significantly increased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Conclusion Silencing lnRNA HOTAIR can target TSC1 to regulate the activity,apoptosis rate,inflammatory level and oxidative stress levels of podocyte injury in DN,thereby alleviating podocyte damage in DN.

Objective To systematically evaluate the risk prediction models for neonatal early-onset sepsis(EOS),aiming to provide reference for the construction and optimization of models,as well as for clinical selection of appro-priate prediction models.Methods PubMed,Web of Science,Embase,Cochrane Library,China National Know-ledge Infrastructure(CNKI),Wanfang Data,China Biology Medicine disc(CBM),and VIP databases were re-trieved,and studies relevant to neonatal EOS risk prediction models were collected.The retrieval period was from the inception of the database to January 18,2025.Two researchers independently screened literatures,extracted da-ta,and evaluated the quality of the included literatures using PROBAST tool.Any disagreements were resolved through consultation with a third reviewer.Results A total of 14 literatures were included in analysis,containing 19 risk prediction models.The area under receiver operating characteristic(ROC)curve(AUC)of the included model ranged 0.71-0.999.The number of prediction factors ranged 3-21.Common prediction factors included young gestational age,low birth weight,1-minute Apgar score,abnormal neonatal temperature,prolonged prema-ture rupture of membranes,amniotic fluid turbidity,maternal Group B streptococcal infection,maternal chorioam-nionitis,as well as elevated levels of procalcitonin and C-reactive protein in neonates.The risk of model overall bias was high,mainly due to insufficient number of outcome variable events in the analysis field,improper processing of missing data,screening of prediction factors based on univariate analysis,lacking model performance evaluation,and overfitting of model.Conclusion The neonatal EOS risk prediction model is still at the development stage.Al-though the current prediction models have better overall predictive performance,the overall quality needs to be im-proved.Future modeling can follow the PROBAST and TRIPOD specifications to reduce bias risk,explore the com-bination of multiple modeling methods,and focus on strengthening external validation and localized application to enhance the clinical applicability and promotion value of the model.

Objective To systematically evaluate the risk prediction models for neonatal early-onset sepsis(EOS),aiming to provide reference for the construction and optimization of models,as well as for clinical selection of appro-priate prediction models.Methods PubMed,Web of Science,Embase,Cochrane Library,China National Know-ledge Infrastructure(CNKI),Wanfang Data,China Biology Medicine disc(CBM),and VIP databases were re-trieved,and studies relevant to neonatal EOS risk prediction models were collected.The retrieval period was from the inception of the database to January 18,2025.Two researchers independently screened literatures,extracted da-ta,and evaluated the quality of the included literatures using PROBAST tool.Any disagreements were resolved through consultation with a third reviewer.Results A total of 14 literatures were included in analysis,containing 19 risk prediction models.The area under receiver operating characteristic(ROC)curve(AUC)of the included model ranged 0.71-0.999.The number of prediction factors ranged 3-21.Common prediction factors included young gestational age,low birth weight,1-minute Apgar score,abnormal neonatal temperature,prolonged prema-ture rupture of membranes,amniotic fluid turbidity,maternal Group B streptococcal infection,maternal chorioam-nionitis,as well as elevated levels of procalcitonin and C-reactive protein in neonates.The risk of model overall bias was high,mainly due to insufficient number of outcome variable events in the analysis field,improper processing of missing data,screening of prediction factors based on univariate analysis,lacking model performance evaluation,and overfitting of model.Conclusion The neonatal EOS risk prediction model is still at the development stage.Al-though the current prediction models have better overall predictive performance,the overall quality needs to be im-proved.Future modeling can follow the PROBAST and TRIPOD specifications to reduce bias risk,explore the com-bination of multiple modeling methods,and focus on strengthening external validation and localized application to enhance the clinical applicability and promotion value of the model.

Objective To investigate the modeling elements of various types of animal models for acute liver injury,and to provide references and suggestions to establish and evaluate animal models of acute liver injury(ALI).Methods The animal experimental literature of ALI from 2002 to 2022 was searched in the databases of the China Knowledge Network,WanFang,Chongqing Vip(VIP),Chinese Medical Journal Full Text Data(Yiigle),and PubMed.The animal species,positive control drugs,modeling method,modeling drugs,and drug administration of the animal models of ALI in the literature were summarized.The result were analyzed using Excel,SPSS Modeler 18.0,and Cytoscape 3.8.2.Results A total of 896 articles were included in the databases.The most used animal models for ALI were male KM mice.The modeling method were mainly chemical liver injury,alcoholic liver injury,drug-related liver injury,and immune liver injury.①The corresponding main modeling method were intraperitoneal injection of 10 mL/kg of 0.1％CC14 in vegetable oil at 24 h before experiments,②gavage of 12.0 mL/kg of 50.0％～56.0％ethanol at 16 h before experiments,③intraperitoneal injection of 300 mg/kg APAP at 24 h before experiments,④tail vein injection of 20 mg/kg Con A at 8 h before experiments.Evaluation of the models was based on liver pathological indexes as the gold standard combined with biochemical indexes of serum ALT,AST,and SOD and MDA contents and activities in liver tissue homogenate as direct indicators.Conclusions Because the causes of ALI vary in clinical practice,the preparation of animal models of ALI should be based on the specific study content and characteristics,and the corresponding modeling method should be selected.

ObjectiveTo compare the effects of topical application of Modified Sanhuang Powder （加味三黄散， MSP） combined with cold compression versus cold compression alone on swelling and pain after knee arthroscopy through a retrospective cohort study. MethodsMedical records of 134 patients with knee arthroscopy-induced knee swelling and pain were divided into non-exposure group （51 cases） and exposure group （83 cases） based on whether they used MSP for external application after surgery. The non-exposure group received simple cold compression therapy in addition to functional exercise and routine treatment after surgery， while the exposure group received topical MSP on the basis of what were given in the non-exposure group. The Visual Analog Scale （VAS） scores were compared between the two groups before and 7 days after treatment， and knee swelling measurements were taken before and 3， 5， and 7 days after treatment. The clinical effective rate was compared between the two groups. ResultsThe VAS scores in both groups were lower after treatment （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. On the 3rd， 5th， and 7th days of treatment， the scores on swelling at 2 cm above the superior pole of the patella， at the midline of the patella， and 5 cm below the inferior pole of the patella significantly decreased after treatment in both groups （P＜0.05）， and the exposure group had lower scores than the non-exposure group （P＜0.05）. The total clinical effective rate in the exposure group was 91.56% （76/83）， which was higher than 78.43% （40/51） in the non-exposure group （P＜0.05）. ConclusionTopical application of MSP combined with cold compression is effective in relieving postoperative swelling and pain after knee arthroscopy and is superior to cold compress alone.

Objective:To evaluate the effects of vaccine switch on the levels of neutralizing antibody (NA) of poliovirus in children aged<12 years.Methods:Subjects aged<12 years from 9 districts in Fujian province were chosen by stratified cluster and complete random sampling method. Blood samples were collected for testing NA of poliovirus by microcell neutralization.Results:A total of 2 134 subjects aged<12 years were selected. The positive rate of NA against PVⅠand Ⅲ were 98.64% and 95.83%; and geometric mean titers (GMTs) were 1∶259.35 and 1∶105.14, respectively. The GMTs presented a trend of decreasing as age increased. Compared to trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV) and inactivated poliovirus vaccine (IPV) induced higher GMTs of NA against poliovirusⅠand Ⅲ respectively. Among 182 children aged<5 years, the positive rate of NA against PVⅠ, Ⅱ, Ⅲ were 97.25%, 76.37% and 92.86%. There were statistical differences among the three types ( χ2=44.44, P=0.000). The rate of NA against PVⅡwas significantly lower than those ofⅠand Ⅲ (Ⅱ vs. I: χ2=34.65, P=0.000; Ⅱ vs. Ⅲ: χ2=18.99, P=0.000). And the GMTs of NA against PV Ⅰ, Ⅱ, Ⅲ were 1∶368.96、1∶23.06 and 1∶183.10, which were significantly different ( F=156.54, P=0.000). The GMT of PVⅠwas the highest, PV Ⅲ was the second, PVⅡ was lowest (pairwise comparison showed values of P all were 0.000). The analysis of general linear model showed that the interval between the date of last immunization and the date of sample collection would affect the GMTs of PVⅠand Ⅲ, different vaccine models would affect only the GMT of PV Ⅰ. The age maybe was a confounding factor. But no factors would affect the GMT of PV Ⅱ. Conclusions:After the vaccine switch, the level of NA against PVⅠand PV Ⅲ were still maintaining high level, but the level of PVⅡamong children<5 years was at relatively low level, which indicated that the surveillance should be strengthened.

Objective:To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome.Methods:The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc.Results:Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4.Conclusions:The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective To evaluate the inactivation effect of heat inactivation and three common chemical disinfectants on enterovirus group A 71 (EV-A71),provide basic data for disinfection work after laboratory activities in enterovirus secondary biosafety laboratory.Methods EV-A71 virus was treated at different temperatures and different disinfectant concentrations according to different time.The inactivated virus was inoculated into 96-well cell culture plates,and the cytopathic effect was observed and recorded.Finally,the virus titer of the virus treatment solution was calculated.Results After inactivation at 56 ℃ for 30 min,the inactivation logarithm of EV-A71 was more than 6,and inactivation at 65 ℃ for 30 rin,70 ℃ for 10 min,no infection was observed.Three chemical disinfectants could effectively inactivate a certain titer of EV-A71 at a certain concentration and treatment time.Conclusions The inactivation effect of EV-A71 virus is related to factors such as thermal inactivation temperature,chemical disinfectant concentration,and treatment time.Studying the inactivation curve of EV-A71 is beneficial to the selection of inactivation conditions in different inactivation environments.