OBJECTIVE To explore the significance of pharmaceutical care through the diagnosis and treatment of a patient with exogenous insulin autoimmune syndrome （EIAS）， combined with the analysis of literature reports. METHODS Clinical pharmacist participated in the diagnosis and treatment process of one case of EIAS. Based on the characteristics of the patient’s condition， the pharmacist provided medication suggestions and formulated pharmaceutical monitoring measures. At the same time， the pharmacist searched for relevant literature on insulin autoimmune syndrome （IAS） and EIAS， extracted data （gender， age， occurrence time， laboratory tests， clinical symptoms， intervention and outcome）， and conducted analysis. RESULTS Based on the patient’s medication information in the past 3 years， clinical pharmacist determined that the EIAS was likely caused by insulin aspartate 30. The clinician adopted the clinical pharmacist’s suggestion to discontinue insulin and switch to oral hypoglycemic drugs. The patient improved after treatment. The literature analysis showed that among the 257 patients with IAS reported， 212 cases were caused by drugs； among them， 23 cases were caused by lipoic acid， and 56 cases were caused by exogenous insulin. There were no significant differences in age， glycosylated hemoglobin， and body mass index between the two groups. The lowest blood glucose level in the lipoic acid group was significantly lower than that in the exogenous insulin group （P＜0.05）. The proportion of females and the proportion of fasting insulin ≥ 1 000 μU/mL were significantly higher in the lipoic acid group than in the exogenous insulin group （P＜0.05）. CONCLUSIONS Compared with EIAS， lipoic acid-induced IAS usually causes more severe hypoglycemia， and the fasting insulin level is usually higher than 1 000 μU/mL， which is more common in female patients. The participation of clinical pharmacists in the diagnosis and treatment of EIAS can help improve the diagnosis and treatment level of similar rare diseases and ensure the safety of patients’ medication.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

BACKGROUND:Previous studies have shown that puerarin can inhibit the differentiation of osteoclasts,and the expression of Notch signaling pathway-related proteins such as Notch1,HES1,and Jagged1 is decreased.However,the specific mechanism of the Notch1 signaling pathway for the inhibition of osteoclast differentiation by puerarin is not clear. OBJECTIVE:To explore the effect of Notch signaling pathway on puerarin inhibiting the differentiation of mouse macrophage Raw264.7 into osteoclasts. METHODS:Raw264.7 cells were divided into seven groups for intervention culture.Blank control group was cultured in high-sugar DMEM medium;the osteoclast induction group was cultured in osteoclast induction medium;the puerarin intervention group was cultured with 50 μmol/L puerarin at the same time of osteoclast induction;Notch1 siRNA control group,Notch1 siRNA group,Notch1 overexpression control group and Notch1 overexpression group were transfected with Notch1 siRNA control sequence,Notch1 siRNA,Notch1 overexpression control plasmid and Notch1 overexpression plasmid,respectively,and then cultured with osteoclast induction medium and puerarin.The number and size of osteoclasts were observed by tartrate-resistant acid phosphatase staining,the skeleton formation of osteoclasts was observed by F-actin staining,and the gene expression level of osteoclast formation markers was detected by RT-PCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining results showed that puerarin intervention could inhibit the generation of osteoclasts,Notch1 silencing could further reduce the number of osteoclasts,while the number of osteoclasts in the osteoclast-induced group increased significantly after Notch1 overexpression.The results of F-actin showed that Raw264.7 cells could form a well-defined F-actin ring after osteoclast induction.Puerarin intervention would inhibit the formation of cytoskeleton,and Notch1 silencing could aggravate the inhibitory effect of cytoskeleton formation,while Notch1 overexpression could alleviate this inhibitory effect of puerarin.RT-PCR results showed that puerarin could inhibit the mRNA expression levels of tartrate-resistant acid phosphatase,Cathepsin K and c-Fos,the expression of the above-mentioned three factors decreased significantly after Notch1 gene silencing,and Notch1 overexpression could upregulate the expression of these factors.These finding indicate that puerarin inhibits the differentiation of Raw264.7 cells into osteoclasts through the Notch signaling pathway.

Objective:To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14.Methods:A child who had presented at the Henan Provincial People′s Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis.Results:The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c. 1609G>A (p.V537M) in exon 17 and c. 802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+ PP3+ PP4). Conclusion:The c. 1609G>A (p.V537M) and c. 802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Objective To investigate the protective effect of Qianggukangwei Recipe(QG)on myotube cell atrophy induced by simulated microgravity effect(SMG).Methods The induced differentiation mouse myotube cells(C2C12 cells)were divided into six groups.Then the 48h simulated microgravity effect(SMG)model of mouse myotube cells was established by three-dimensional gyrotron(48h-SMG group).The cells in 3 groups were treated with 2.50,1.25,0.625 mg/mL QG.The cells in the left group were treated with 2.70 μg/mL alendronate sodium as positive control group.The levels of oxidative and inflammatory factors in myotube cells were detected by kits.The protein expression levels of NF-κB/IκB protein decomposition pathway and IGF-1/PI3K/Akt protein synthesis pathway were detected by Western blotting.The IGF-1/PI3K/Akt pathway was verified by 7 μmol/L of IGF-1 inhibitor.Results As compared with the control group,oxidation and inflammation levels in myotube cells increased significantly(P<0.05).The protein expression levels of IKK,NF-κB,and MURF-1 were significantly increased by 19.9%±6.1%,189.3%±15.9%,445.0%±46.1%,and IκB was significantly decreased by 26.5%±0.1%(P<0.05).The levels of IGF-1,PI3K,p-Akt/Akt and mTOR in the IGF-1/PI3K/Akt pathway were decreased by 23.6%±0.5%,30.7%±2.7%,13.3%±1.1%,21.0%±1.6%(P<0.05).The three doses of QG could and reduce the level of cellular oxidative stress and inflammation(P<0.05).QG could also activate the IGF-1/PI3K/Akt pathway and inhibit the NF-κB/IκB pathway.Among them,the high dose of QG(2.50 mg/mL)significantly decreased the protein expression levels of IKK,NF-κB and MURF-1 by 39.9%±2.4%,48.6%±0.1%,70.0%±2.1%(P<0.05),and significantly increased the expression levels of IGF-1,PI3K,mTOR and Akt phosphorylation by 43.1%±1.1%,100.0%±7.7%,71.8%±2.5%,95.2%±12.8%(P<0.05).Conclusion QG can significantly alleviate myotube cell atrophy induced by SMG effect by regulating relevant protein synthesis and degradation pathways.

Objective:To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally.Methods:The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software.Results:DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group ( P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion:The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.

Objective To explore the association between peripheral retinal defocus and myopia in adolescents.Methods This study encompassed 192 adolescents(192 right eyes),aged between eight and fifteen years,who sought treatment at Ineye Hospital of Chengdu University of TCM from October 2022 to April 2023.Based on the spherical equiva-lent(SE),the patients were divided into three groups:Emmetropia(E),low myopia(LM),and moderate myopia(MM),with each group comprising 64 patients(64 right eyes).After mydriatic refraction,the SE values were documen-ted.Ocular biological parameters,including axial length(AL),central corneal thickness(CCT),lens thickness(LT),and keratometry values(K1,K2),were obtained using IOL Master 900.Multispectral refraction topography was employed to measure the retinal defocus:positive values indicated hyperopic defocus,while negative ones represented myopic defocus.With the macular fovea as the center,the total retinal defocus value was recorded as TRDV.The ring partition(eccentrici-ty)was divided into 0°-10°、＞10°-20°、＞20°-30°、＞30°-40°、＞40°-53°,which was recorded as RDV-0°-10°,RDV-10°-20°,RDV-20°-30°,RDV-30°-40°,and RDV-40°-53°,respectively;the quadrants were recorded as RDV-Superior(RDV-S),RDV-Inferior(RDV-I),RDV-Temporal(RDV-T)and RDV-Nasal(RDV-N),respectively.The variance of RDV across different ranges was analyzed using One-Way ANOVA and non-parametric tests.The associations between SE,AL and RDV were examined using Spearman and Pearson correlation analyses.Results The RDV-20°-30°,RDV-30°-40° and RDV-40°-53° of Groups E,LM and MM all exhibited hyperopic defocus.Statistically significant differences were identi-fied in TRDV,RDV-10°-20°,RDV-20°-30°,RDV-30°-40°,RDV-40°-53°,RDV-S,RDV-T and RDV-N among the three groups(all P＜0.05).TRDV,RDV-20°-30°,RDV-30°-40°,RDV-40°-53°,RDV-S,RDV-T,and RDV-N were found to be negatively correlated with SE while positively correlated with AL(all P＜0.05).RDV-0°-10° and RDV-I were uncorrelated with both SE and AL(all P＞0.05);RDV-10°-20° was positively correlated with AL(P=0.012)while uncorrelated with SE(P=0.233).Conclusion Peripheral retinal hyperopic defocus tends to advance with escalating eccentricity and my-opia.Peripheral retinal defocus is asymmetrical.Peripheral(10°-53°),superior,nasal and temporal retinal defocus may be closely related to the development of myopia.

Objective To explore the changes in periretinal defocus and visual quality after femtosecond laser-assis-ted in situ keratomileusis(FS-LASIK).Methods Fifty-one myopic patients(102 eyes)who underwent FS-LASIK at the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from March to May 2023 were selected for the study,including 27 females(54 eyes)and 24 males(48 eyes).The defocus around the retina was measured using a multispectral refraction topography,and the total refraction difference value(TRDV)was recorded.The refraction difference value(RDV)in four quadrants:superior RDV(RDV-S),inferior RDV(RDV-I),nasal RDV(RDV-N),and temporal RDV(RDV-T),as well as the RDV in the concentric ring areas corresponding to 10°,20°,30°,40°,and 53° from the fovea of the mac-ula(represented as RDV 0°-10°,RDV 10°-20°,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53°,respectively)were also re-corded.The objective scattering index(OSI),Strehls ratio(SR),modulation transfer function(MTF)values(represen-ted as 10 c·d-1 MTF,20 c·d-1 MTF,and 30 c·d-1MTF,respectively)and cutoff frequencies(MTF cutoff)at the spa-tial frequencies of 10 c·d-1,20 c·d-1 and 30 c·d-1 were measured and recorded using a visual quality analysis system.The data of corneal vertical trefoil(Z3-3),vertical coma(Z3-1),horizontal coma(Z31),horizontal trefoil(Z33),vertical tetrafoil(Z4-4),vertical secondary astigmatism(Z4-2),spherical aberration(Z40),horizontal secondary astigmatism(Z42),horizontal tetrafoil(Z44),and total higher-order aberration(HOA)were measured and recorded using the iTrace aberration meter.The measurement data of patients before surgery,one month after surgery,and three months after sur-gery were compared,and their correlations were analyzed.Results TRDV,RDV-S,RDV-N,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53° around the retina of patients decreased one month and three months after surgery compared with those be-fore surgery,and the differences were statistically significant(all P＜0.001).There were statistically significant differences in OSI,MTF cutoff,and 10 c·d-1 MTF among patients before surgery,one month after surgery,and three months after surgery(all P＜0.05).There were statistically significant differences in corneal Z3-3,Z3-1,Z31,Z33,Z4-4,Z4-2,Z40,Z42,Z44,and HOA among patients before surgery,one month after surgery,and three months after surgery(all P＜0.001).The Pearson correlation analysis results showed that,ΔRDV 0°-10° was positively correlated with ΔZ3-3,ΔZ31,ΔZ4-2,ΔZ40,and ΔZ42(all P＜0.05);ΔRDV 10°-20° was positively correlated with ΔZ4-4 and ΔZ4-2(both P＜0.05);ΔRDV 20°-30° was positively correlated with ΔZ4-4 and ΔZ44(both P＜0.05);ΔTRDV and ΔRDV 40°-53° were negatively correla-ted with ΔHOA(both P＜0.05).ΔRDV-S and ΔZ3-1 were negatively correlated with ΔHOA(both P＜0.05)and positively correlated with ΔZ44(P＜0.05);ΔRDV-N was positively correlated with ΔZ4-4(P＜0.05).Conclusion FS-LASIK can reduce periretinal hyperopic defocus in myopic patients,but it introduces corneal HOA,and there is a certain correlation between the two.