ObjectiveTo investigate the molecular mechanisms by which Wenyang Jiedu granules （WYJD） alleviate influenza A virus （IAV）-induced pneumonia based on single-cell transcriptome sequencing. MethodsThirty female BALB/c mice were randomly divided into a blank control group （Control）， IAV group， and WYJD low-， medium-， and high-dose groups （WYJD-L， WYJD-M， WYJD-H； 2.925， 5.85， 11.7 g·kg^-1， n=6）. Except for the Control group， all other groups were intranasally inoculated with IAV subtype H1N1 （A/PR/8/34） to establish an infection model. Two hours after modeling， drug administration was initiated and continued for 5 consecutive days， with daily monitoring of body weight and general condition. On day 6， mice were sacrificed and samples were collected. Lung index was calculated， and histopathological examination of lung tissue was performed. Lung tissues from the Control， IAV， and WYJD-H groups were subjected to single-cell transcriptome sequencing （n=3）， focusing on type I alveolar epithelial cells （AT1） to analyze changes in gene expression and signaling pathways. Western blot was used to detect the expression changes of relevant proteins to validate the single-cell sequencing results. ResultsCompared with the Control group， the IAV group exhibited significantly decreased body weight （P<0.05） and significantly increased lung index （P<0.05）. Compared with the IAV group， all WYJD-treated groups exhibited significantly increased body weight （P<0.01） and significantly decreased lung index （P<0.01）. Single-cell sequencing analysis revealed that WYJD inhibited overactivation of interferon and inflammatory signaling pathways in AT1 cells after IAV infection， including interferon-γ response， interferon-α response， tumor necrosis factor-α/nuclear factor-κB （TNF-α/NF-κB）， and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 （IL-6/JAK/STAT3） pathways. Compared with the Control group， the number of AT1 cells in the IAV group showed a decreasing trend. Compared with the IAV group， the WYJD-H group showed an increasing trend， although neither difference was statistically significant. Further analysis of AT1 cell subpopulation gene expression showed that， compared with the Control group， the IAV group exhibited increased expression of pro-apoptotic genes FAS cell surface death receptor （FAS） and cyclin-dependent kinase inhibitor 1A （CDKN1A）， a significant increase in tumor protein p53 （Tp53） expression （P<0.05）， and significant decreases in expression of the AT1 marker gene advanced glycosylation end-product-specific receptor （AGER） and membrane structural gene caveolin1 （CAV1） （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of FAS， CDKN1A， and Tp53 （P<0.05， P<0.01）， and significantly increased expression of AGER and CAV1 （P<0.05， P<0.01）. Regarding interferon response-related genes， compared with the Control group， the IAV group showed increased expression of interferon-stimulated gene 15 （ISG15）， interferon-induced protein with tetratricopeptide repeats 3 （IFIT3）， signal transducer and activator of transcription 2 （STAT2）， bone marrow stromal cell antigen 2 （BST2）， and C-X-C motif chemokine ligand 10 （CXCL10）， with a significant increase in 2′，5′-oligoadenylate synthetase-like protein 1 （OASL1） （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of all the above genes， with highly significant differences for ISG15， IFIT3， STAT2， BST2， and OASL1 （P<0.01）， and a significant difference for CXCL10 （P<0.05）. Among inflammation-related genes， compared with the Control group， the IAV group showed significantly increased expression of intercellular adhesion molecule 1 （ICAM1）， tumor necrosis factor alpha-induced protein 3 （TNFAIP3）， keratin 8 （KRT8）， tumor necrosis factor receptor superfamily member 1A （TNFRSF1A）， and TNFRSF1B （P<0.01）， and increased expression of NFKBIA， a negative regulator of NF-κB （P<0.05）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of KRT8 and TNFRSF1B （P<0.05）， while ICAM1， NFKBIA， TNFAIP3， and TNFRSF1A showed decreasing trends without statistical significance. Western blot validation showed that， compared with the Control group， protein expression levels of ISG15， FAS， p53， and phosphorylated p65 （p-p65） in lung tissue of the IAV group were significantly increased （P<0.05， P<0.01）. Compared with the IAV group， the WYJD-H group showed significantly decreased expression of these proteins （P<0.05， P<0.01）. ConclusionWYJD may alleviate viral pneumonia by targeting gene expression in AT1 cells， inhibiting overactivated interferon and inflammatory signaling pathways after IAV infection， and downregulating pro-apoptotic signaling， thereby reducing alveolar epithelial injury.

Objective In order to address the issues of inconvenience,high medical costs,and lack of universality associated with traditional knee rehabilitation equipment,a portable intelligent wheelchair for knee rehabilitation was designed in this study.Methods Based on the analysis of the knee joint's structure and rehabilitation mechanisms,an electric pushrod-driven rehabilitation institution was developed.A multi-functional module was designed with a modular approach,and the control of the wheelchair body and each functional module was implemented using an STM32 single-chip microcomputer.A three-dimensional model was established using SolidWorks software.In conjunction with Adams and Ansys simulation software,kinematic and static analyses were conducted on the knee joint rehabilitation institution and its core components.A prototype was constructed to verify the equipment's actual performance.Results According to the prototype testing,the actual range of motion for the knee joint swing rod is 15.1°～88.9°,the angular speed of the swing rod ranges from-7.9 to 8.1°/s,the angular acceleration of the swing rod varies from-4.2 to 1.6°/s2,the thrust range of the electric pushrod is-82.6 to 153.1 N,and the maximum displacement of the load pedal is approximately 1.7 mm,with the leg support exhibiting a maximum deformation of about 1.5 mm.Conclusion The intelligent knee joint rehabilitation wheelchair meets the designed functions and its actual performance aligns with the design criteria,thus validating the rationality and feasibility of the structural design.

Objective:To investigate the current status of knowledge, attitudes, and practices (KAP) regarding insulin injection among clinical nurses in a Macao, China hospital and to analyze the influencing factors.Methods:From October to December 2022, 350 clinical nurses from Kiang Wu Hospital in Macao were selected as study subjects by cluster sampling. A questionnaire was employed to gather data on their demographics, experience with insulin injection protocols, and their KAP regarding insulin injection. Univariate analysis and multiple linear regression analysis were conducted to explore the factors influencing nurses' KAP regarding insulin injection.Results:The KAP score for insulin injection among the 350 clinical nurses was (185.71±17.29). Multiple linear regression analysis indicated that the department of work, having received standardized insulin injection training in the past year, providing insulin injection education to diabetic patients, and awareness of the hospital's insulin injection guidelines were significant influencing factors of the KAP score ( P<0.05) . Conclusions:The overall KAP scores regarding insulin injection among the surveyed clinical nurses are good. Nurses demonstrate strong attitudes and practices toward insulin injection, but their knowledge is relatively weaker. Future studies should expand the scope of standardized insulin injection training in clinical settings and provide supportive resources for related training courses for nurses.

AIM:To explore the effects of moderate-altitude exposure on intestinal flora in healthy individuals.METHODS:The aid-Tibet cadres,who were sent to work from Guangdong(average altitude<50 m)to Nyingchi(average altitude of 2 900 m),were recruited.A total of 76 samples were collected,including 42 samples from healthy adults with plateau living for 0 day and 34 samples from healthy adults with plateau living for 6 months.Fecal samples DNA were ex-tracted,sequenced by the 16S rDNA high-throughput sequencing technology and analyzed bioinformatically.RESULTS:Compared with the base group,α diversity was increased(P=4.00×10-4)and β diversity was decreased(P=1.00×10-3).After moderate altitude exposure,the relative abundance of phylum Proteobacteria(|LDA|>4,P<0.05),genus Escherich-ia-Shigella,species Enterococcus_faecalis,Haemophilus_influenzae and Helicobacter_sp._UNSW1.7sp decreased(adjust-ed P<0.05),wheras the relative abundance of phylum Bacteroidetes(|LDA|>4,P<0.05),genus Butyricimona,species Lactobacillus_sp._RA2113(s)and Butyricimonas_sp._Marseille-P2440(s)increased(adjusted P<0.05).The function-al prediction by PICRUSt showed a decrease in the relative abundance of pathway related to xenobiotics biodegradation and metabolism,membrane transport and amino acid metabolism(adjusted P<0.05).Conversely,the relative abundance of pathway related to biosynthesis of other secondary metabolites and nucleotide metabolism was increased(adjusted P<0.05).Finally,the results of microbiome phenotype prediction by BugBase showed that moderate altitude exposure im-proves the gut microbiota functions involving anaerobic oxygen tolerance and gram positive(adjusted P<0.05).And bacte-ria containing facultatively anaerobic oxygen tolerance,oxidative stress tolerance,gram negative and biofilm formation in the six-group decreased significantly compared with those in base group(adjusted P<0.05).CONCLUSION:Moderate altitude exposure impacts the diversity,abundance and function of intestinal flora in healthy population,suggesting that al-titude factors may have some influence on gut microbiota.

Objective Network Meta-analysis was used to compare and estimate the therapeutic effect and safety of oral Chinese patent drugs in treatment of diabetic peripheral neuropathy(DPN).Methods PubMed,Cochrane Library,EMbase,Web of Science,China National Knowledge Infrastructure(CNKI),Chinese Citation Database(CCD),China Science Periodical Database(CSPD)and SinoMed was retrieved to collect randomized controlled trials(RCTs),which were related to oral Chinese patent drugs in treatment of DPN.Cochrane Handbook 5.3 was used to assess the quality of the studies,and Stata 15 and ADDIS 1.16.5 were utilized to analyse data.Results 48 RCTs were included,including 4200 patients,involving 11 kinds of Chinese patent drugs.In terms of improving clinical total effective rate,the top three interventions were mecobalamin combined with Tangmaikang granules,Jinlida granules and Naoxintong capsules.The top three interventions for improving toronto clinical scoring system(TCSS)were mecobalamin combined with Mailuoning peroral liquids,Mudan granules and Xuefuzhuyu capsules.In the aspect of improving sensory conduction velocity(SCV)of median nerve,the top three interventions were mecobalamin combined with Tongxinluo capsules,Xuesaitong soft capsules and Fufangxueshuantong capsules.The top three interventions for improving SCV of peroneal nerve were mecobalamin combined with Xuefuzhuyu capsules,Jinlida granules and Mailuoning peroral liquids.In terms of improving motor conduction velocity(MCV)of median nerve,the top three interventions were mecobalamin combined with Tongxinluo capsules,Yindanxinnaotong soft capsules and Tangmaikang granules.The top three interventions for improving MCV of peroneal nerve were mecobalamin combined with Xuesaitong soft capsules,Yindanxinnaotong soft capsules and Tongxinluo capsules.In the terms of improving blood glucose,several studies reported that Tangmaikang granules and Tongmaijiangtang capsules combined with mecobalamin could improve the level of glycated hemoglobin(HbA1c),which was superior to mecobalamin alone.Compared with mecobalamin alone,mecobalamin combined with Chinese patent drugs did not increase the occurrence of adverse reactions.Conclusion Mecobalamin combined with Chinese patent drugs can improve the therapeutic effect,TCSS scores and nerve conduction velocity,and the safety is satisfactory,which can provide some reference for clinical medication.

Objective Network Meta-analysis was used to compare and estimate the therapeutic effect and safety of oral Chinese patent drugs in treatment of diabetic peripheral neuropathy(DPN).Methods PubMed,Cochrane Library,EMbase,Web of Science,China National Knowledge Infrastructure(CNKI),Chinese Citation Database(CCD),China Science Periodical Database(CSPD)and SinoMed was retrieved to collect randomized controlled trials(RCTs),which were related to oral Chinese patent drugs in treatment of DPN.Cochrane Handbook 5.3 was used to assess the quality of the studies,and Stata 15 and ADDIS 1.16.5 were utilized to analyse data.Results 48 RCTs were included,including 4200 patients,involving 11 kinds of Chinese patent drugs.In terms of improving clinical total effective rate,the top three interventions were mecobalamin combined with Tangmaikang granules,Jinlida granules and Naoxintong capsules.The top three interventions for improving toronto clinical scoring system(TCSS)were mecobalamin combined with Mailuoning peroral liquids,Mudan granules and Xuefuzhuyu capsules.In the aspect of improving sensory conduction velocity(SCV)of median nerve,the top three interventions were mecobalamin combined with Tongxinluo capsules,Xuesaitong soft capsules and Fufangxueshuantong capsules.The top three interventions for improving SCV of peroneal nerve were mecobalamin combined with Xuefuzhuyu capsules,Jinlida granules and Mailuoning peroral liquids.In terms of improving motor conduction velocity(MCV)of median nerve,the top three interventions were mecobalamin combined with Tongxinluo capsules,Yindanxinnaotong soft capsules and Tangmaikang granules.The top three interventions for improving MCV of peroneal nerve were mecobalamin combined with Xuesaitong soft capsules,Yindanxinnaotong soft capsules and Tongxinluo capsules.In the terms of improving blood glucose,several studies reported that Tangmaikang granules and Tongmaijiangtang capsules combined with mecobalamin could improve the level of glycated hemoglobin(HbA1c),which was superior to mecobalamin alone.Compared with mecobalamin alone,mecobalamin combined with Chinese patent drugs did not increase the occurrence of adverse reactions.Conclusion Mecobalamin combined with Chinese patent drugs can improve the therapeutic effect,TCSS scores and nerve conduction velocity,and the safety is satisfactory,which can provide some reference for clinical medication.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Objective:To elucidate the molecular mechanism(s) by which methyl salicylate enhances the skin de-livery of herbal ingredients with diverse lipophilicity.Methods:The toxicity of methyl salicylate on skin cell lines was evaluated using the MTT assay.The Franz diffusion cell method was used to measure the permeability enhancing activities of methyl salicylate for five herbal ingredients with a range of lipophilicities.The interaction between methyl salicylate and the stratum corneum (SC) was observed by using an infrared spectroscopy technique.Moreover,the solu-bilities and SC-vehicle partition coefficient were determined to monitor the impact of methyl salicylate on the drug thermodynamic activities and partition into the SC layer,respectively.Results:Compared with azone (1-dodecylazacycloheptan-2-one),methyl salicylate showed lower toxicity to skin cells in terms of the ICso values.The in vitro skin permeation studies showed that methyl salicylate could greatly improve the cumulative amounts or steady state flux of the selected model drugs with the exception of osthole,which indicated that methyl salicylate was prone to promote the skin delivery of hydrophilic drugs.The Fourier transform infrared spectroscopy studies revealed that methyl salicylate mainly interacted with SC lipids,leading to the disruption of the orderly arrangement of the SC.In addition,methyl salicylate had no obvious effect on the drug thermodynamic activity and partition into the SC.Conclusion:Methyl salicylate could effectively promote the skin delivery of relatively hydrophilic in-gredients in externally used traditional Chinese medicines (TCM) without obvious cytotoxicity.

Objective To study the relationship between the cognitive function and speech recognition ability in young patients with OSAHS.Methods We selected 60 young male patients,according to the apnea-hypopnea index(AHI)and the severity of hypoxemia.They were divided into three subgroups on the basis of their syndrome severities:mild group (n= 19;AHI 5~15/h,85%≤minimum SaO2≤90%),moderate group (n= 20;AHI>15~30/h,80%≤minimum SaO2<85%),and severe group (n= 21;AHI>30/h,minimum SaO2<80%).First,we used the MoCA scale for cognitive function tests and recorded the scores.Then 15 lists of sentence Mandarin Speech Test Materials(MSTMs)were utilized to test each group.A data analysis was performed using SPSS 17.0 software. Results The total MoCA scores(mild group:27.32±1.16;moderate group:25.85±1.23;severe group:24.52± 1.69;control group:28.52 ±1.16)decreased progressively as the disease severity increased,showing significant differences between the control group and the mild,moderate and severe groups of OSAHS patients (allP<0.05). When sound stimuli were presented at 22,24,and 26 dB SPL,the speech recognition rates in the patients with se-vere(35.4±22.6,56.3±23.9,75.2±16.5)lower than the other groups (mild group:38.4±23.5,58.3±25.5,79.2 ±18.5;moderate group:38.8±21.6,58.7±22.7,78.5±16.7;control group:39.4±23.5,60.3±24.3,80.2±16.4, respectively,allP<0.05).The differences in intensity of 50% recognition rate between the severe group(4.15± 0.80)and the control(3.62±0.41),mild (3.66±0.50)and moderate groups(3.72±0.55)of OSAHS patients were statistically significant(allP<0.05).Conclusion With hypoxia and disease severity increased,speech recogni-tion abilities in OSAHS patients decreased.This may be an important factor associated with cognitive assessment scale score.

Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the ex-pression of hypoxia inducible factor-1α(HIF-1α),Bax and Bcl-2, and the mechanism underlying the role of HIF-1αin he-patocyte apoptosis thereof. Methods Sixty rats were randomly divided into four groups: normal control group, rats were treated normally;IH group, rats were treated by 30 s nitrogen and then 90 s air, and rats were treated by from 9:00-17:00 daily;pulmonary emphysema group, rats were treated by smudging for half an hour, twice a day (8:00 and 18:00);IH with pul-monary emphysema group, rats were treated by 30 s nitrogen and then 90 s air from 9:00-17:00 daily. After exposure four-teen weeks, rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA and Bcl-2 mRNA in live tissues. Results The expressions of HIF-1αmRNA, Bax mRNA and Bax/Bcl-2 were significantly higher in IH with pulmonary emphysema group than those in control group,IH group and pulmonary emphysema group (P<0.05). The expression level of Bcl-2 mRNA was significantly lower in IH with pulmonary emphysema group than that of con-trol group and pulmonary emphysema group (P < 0.05), but no significant difference compared with that of IH group (P >0.05). The levels of HIF-1αand Bax were positively correlated with the level of Bax/Bcl-2 (r=0.732 and 0.699),but the lev-els of HIF-1αand Bax were negatively correlated with the level of Bcl-2 (r=-0.705). Conclusion The expression levels of HIF-1αmRNA, Bax mRNA and Bcl-2 mRNA were over-regulated in hepatocytes induced by intermittent hypoxia with pul-monary emphysema. The HIF-1αexpression was correlated with Bax and Bcl-2, suggesting that HIF-1αmay promote the hepatocyte apoptosis through transcriptional co-activators, Bax and Bcl-2.