Objective:To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution(CHAaHGS)on the hair growth through in vitro experiments on the human dermal papilla cells(HDPCs),in vivo experiments in the C57BL/6 mice,and human efficacy tests,and to clarify its potential mechanism.Methods:The HDPCs were divided into control group,CHAaHGS group,and minoxidil group.MTT method was used to detect the proliferation activities of HDPCs in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),insulin-like growth factor-1(IGF-1),and transforming growth factor β1(TGF-β1)in the supernatant of HDPCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of VEGF,HGF,IGF-1,TGF-β1,and alkaline phosphatase(ALP)mRNA in the HDPCs in various groups;Western blotting method was used to detect the expression levels of β-catenin,dishevelled segment polarity protein 1(DVL1),glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and wingless-type MMTV integration site family member 3a(Wnt3a)proteins in the HDPCs in various groups.A total of 18 mice were randomly divided into control group,CHAaHGS group,and minoxidil group,with 6 mice in each group.The mouse hair loss model was established using hair removal cream,and corresponding drug treatments were administered immediately after hair removal.The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected;HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7;ELISA method was used to detect the levels of VEGF,HGF,IGF-1,and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups.Sixty subjects were randomly divided into control group and CHAaHGS group,with 30 subjects in each group.The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0,4,8,and 12.Results:The MTT assay results showed that compared with control group,the proliferation activity of the cells in 50 mg·L-1CHAaHGS group was significantly increased(P＜0.01).The ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.01).The RT-qPCR results showed that compared with control group,the expression levels of VEGF,HGF,IGF-1,and ALP mRNA in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 mRNA expression level was significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of β-catenin,DVL1,p-GSK-3βand Wnt3a proteins in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the GSK-3β protein expression level was significantly decreased(P＜0.05).In animal experiments,on day 21,compared with control group,the length of newly grown hair of the mice in CHAaHGS group was significantly increased(P＜0.05),and the hair weight was significantly increased(P＜0.01).On day 7,the HE staining results showed that compared with control group,the hair follicle spacing of the mice in CHAaHGS group was significantly decreased(P＜0.05),and the number of hair follicles was significantly increased(P＜0.01);the ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.05).In human efficacy test,compared with control group,the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12(P＜0.01),and the local hair density was increased(P＜0.05).Conclusion:CHAaHGS promotes hair growth,and the mechanism may be related to its ability to increase the proliferation activity of HDPCs,induce the secretion of VEGF,HGF,and IGF-1,and activate the Wnt/β-catenin signaling pathway.

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P＜0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3％,AP=0.80)and miR-16(AUC=0.83,79.0％,AP=0.83)than for AFP(AUC=0.74,61.7％,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9％)and the AP to 0.85 and was significantly superior to the other markers in this study(P＜0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

The contents, application progress, application effect and optimization strategy of group pregnancy health care model were reviewed, in order to provide reference for the establishment of standardized intervention and health management practice strategies of rural women′s pregnancy care in line with China′s national conditions.

Mechanical ventilation(MV)provides life support for critically ill respiratory patients,but in the meantime can cause fatal ventilator-induced lung injury(VILI),and the latter remains a major challenge in respiratory and critical care medicine,because the pathological mechanism has not been fully elucidated.Recent studies show that on the one hand,in the lung with VILI,there exists airway collapse at multi-sites of an individual airway,which can not be explained by traditional airway collapse models.But on the other hand,under MV conditions,airway smooth muscle cells(ASMC)exhibit abnormal mechanical behaviors,accompanied by regulation of Piezo1 expression and endoplasmic reticulum stress.These phenomenons indicate that the MV-induced abnormal mechanical behavior of ASMC is closely related to multiple airway collapse and VILI.Therefore,by studying the MV-induced changes of ASMC mechanical behaviors and their relationship with airway collapse in lung injury,as well as the related mechanochemical signal coupling process,it is expected to reveal a novel mechanism of MV-associated airway collapse and lung injury from the perspective of cell mechanics.In this review,the recent research progress of airway collapse during MV,the regulation of ASMC mechanical behavior by MV-related high stretch,especially the related mechanochemical signal coupling mechanism is summarized.These advances may provide a novel insight for exploring the roles of ASMC abnormal mechanical behavior in the pathological mechanism of VILI,alternative targets of drug intervention for prevention and treatment of VILI,as well as for optimizing the ventilation mode in clinical practice.

Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.

Abstract OBJECTIVE To construct an intelligent medical supply chain management platform and explore the closed-loop management model of the entire medical supply chain process. METHODS Identify the problems in the traditional drug supply chain management model of medical institutions and propose the idea of building an intelligent medical supply chain management platform. At the same time, systematically introduce the architecture and management of this platform and evaluates its application effect. RESULT After the implementation of the platform, notable enhancements had been observed in the hospital drug supply chain regarding information and intelligence. Moreover, the work efficiency of the hospital drug supply chain had been improved, facilitated the interconnection of drug information between medical institutions, designated medical security information platforms, and pharmaceutical enterprises. Furthermore, the platform had successfully facilitated "resource sharing and technical support" among these three entities, enabling comprehensive traceability of the entire drug supply chain within the region. CONCLUSION Building an intelligent medical supply chain management platform based on internet information technology can help promote digital reform in hospitals, strengthen pharmaceutical management levels, improve medical service quality and has widespread application value within the industry.

Objective: To study the expression of long non-coding RNA LINC01152 in glioma and its influence on the malignant biological behavior of glioma cells． Methods: LINC01152 expression in glioma was analyzed by LncSpA V2．0 and GEPIA database．qRT-PCR was applied to detect the expression of LINC01152 mRNA in 10 samples of human normal brain tissues，40 samples of glioma tissues and 5 glioma cell lines．GO and KEGG enrichment analysis of LINC01152 co-expressed genes were performed using the DAVID database to predict the related functions． The AnoLnc2，TargetScan，LinkedOmics and miRDB databases were used to predict the LINC01152 related miRNAs and target genes to construct a ceRNA regulatory network．LINC01152 expression was knocked down in glioma cell lines by small interfering RNA (siRNA) transfection．The CCK-8 test，scratch healing experiments，Transwell，flow cytometry and Western blot experiments were used to measure the influence of LINC01152 on the proliferation，migra- tion，invasion and apoptosis of glioma cells. Results : Database analysis showed that compared with other tumor types，LINC01152 was highly expressed in glioblastoma (GBM) and low grade glioma (LGG) ，and was higher than normal brain tissue．qRT-PCR showed that the expression of LINC01152 mRNA in glioma tissues was significantly higher than that in normal brain tissues (P＜0. 01)．The expression of LINC01152 was correlated with Ki-67 (P < 0. 05) ，but not with clinical parameters such as gender，age，tumor size，P53 protein，glial fibrillary acidic protein (GFAP) ，O-6-methylguanine-DNAmethyltransferase ( MGMT) and WHO grade of glioma patients． Functional enrichment analysis of co-expressed genes indicated that the LINC01152 was mainly involved in biological processes such as cell adhesion and synaptic signaling．LINC01152-miRNA-mRNA regulatory network was constructed according to predicted target genes．After down-regulation of LINC01152 expression，the proliferation，migration and invasion abilities of A172 and U87 cells decreased(P＜0. 01) ，while the apoptosis of glioma cells significantly increased (P＜0. 001) ． Conclusion LINC01152 is highly expressed in glioma，which can promote the malignant biological behavior of glioma cells by enhancing proliferation，migration as well as invasion and inhibition of apoptosis.

Objective：To explore the targeting relationship between miR-377-5p and hypoxia inducible factor-1 (HIF-1α), and investigate the regulatory effect of miR-377-5p on proliferation, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells through vascular endothelial growth factor (VEGF) signaling pathway. Methods： ：The expression of miR-377-5p in 35 pairs of human HCC tissues and para-cancerous tissues was detected by qPCR. Then, HepG2 cells were divided into control group, mimic-NC group and miR-377-5pmimicgroup.qPCRwasusedto detect the transfection efficiency; the effects of miR-377-5p over-expression on proliferation and invasion of HepG2 cells were examined by EdU staining and Transwell assay, respectively; and the effect of miR-377-5p over-expression on the expressions of proliferation-related protein Ki-67, proliferating cell nuclear antigen (PCNA) and epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) were detected by Western blotting (WB); the effect of miR-377-5p over-expression on the expression of hypoxia inducible factor-1α (HIF-1α) in HepG2 cells was detected by qPCR and WB; and the targeting relationship between miR-377-5p and HIF-1α gene was determined by Luciferase reporter gene assay. Results: The expression of miR-377-5p in HCC tissues was significantly lower than that in para-cancerous tissues (P<0.01). Compared with the control group, the expression of miR-377-5p in HepG2 cells of miR-377-5p mimic group elevated significantly, and the proliferation, invasion and the expression of N-caderin proteins decreased,significantly (all P<0.01), while the expression of E-caderin increased significantly (P<0.01). At the same time, the mRNA and protein expressions of HIF-1α in miR-377-5p mimic group decreased significantly (P<0.01 or P<0.05). miR-377-5p targetedly inhibited the expression of HIF-1α gene and suppressed the activation of VEGF pathway (all P<0.05). Conclusion: miR-377-5p inhibits the proliferation, invasion and EMT of HepG2 cells via targetedly inhibiting HIF-1α expression and suppressing the activation of VEGF signaling pathway.

Rapid reduction of postprandial blood glucose is very beneficial to diabetics. In order to shorten the onset time of recombinant insulin, the cone snail insulin G1 (cI G1) of Conus geographus was studied. First, the nucleotide sequence of recombinant cone snail proinsulin G1 (cPI G1) was designed and synthesized according to the genes of human proinsulin (hPI) and cPI G1. The codon was optimized according to Escherichia coli (E. coli) codon usage frequency. Then, the plasmid pET22b(+)-cPI G1 was constructed and the recombinant cPI G1 was expressed in E. coli BL21(DE3) host strain. The recombinant cPI G1 was then purified and cleaved specially by trypsin to generate the recombinant cI G1, and its potency is 25.9 IU/mg. Fasting blood glucose test (FBGT) and oral glucose tolerance test (OGTT) suggested that the recombinant cI G1 could rapidly reduce blood glucose in normal and streptozotocin (STZ)-induced diabetic mice, but only for a short duration. This study provides a technical reference for the development of recombinant fast-acting insulin.
Animals ; Conus Snail ; Diabetes Mellitus, Experimental ; Escherichia coli ; Humans ; Hypoglycemic Agents ; Insulin ; Mice

Objective To evaluate the electrocardiographic(ECG)-gated 4-dimensional computed tomographic angiography (4D-CTA) in the determination of pulsation of unruptured cerebral aneurysms (URCAs).Methods This study included 48 patients with 62 URCAs.Examinations of ECG gated 4D-CTA of dual-source CT were performed.Twenty sets of image data with the time intervals of 5％ in a cardiac cycle were obtained after postprocessing on the workstation.The convex was defined as the point of pulsation if small bubble or small pointed convex could be found in continuous three or more images at the same location.The 62 URCAs were divided into two groups based on whether having a point of pulsation.All the URCAs were scanned at the follow-up by 3D-CTA or ECG gated 4D-CTA more than 120 days later.The diameters of aneurysms and aspect ratio between the two groups were compared with independent t test,while neck of aneurysms and follow-up time were compared with two-independent samples Mann-Whitney U test.The other variables including history of hypertension,type 2 diabetes,smoking et al between the two groups were analyzed by x2 test.The sensitivity and specificity of aspect ratio for diagnosis of pulsation were analyzed by receiver operating characteristic (ROC) curve.Results Pulsation was observed in 28 of the 62 URCAs.Aspect ratios in whose pulsation was or was not detected were 1.5±0.3 and 1.1±0.3,respectivelyThe difference between the two groups was statistically significant (t=-2.274,P＜0.001).The sensitivity and specificity of the aspect ratio were 75.0％ and 70.6％.After follow-up more than 3 months,of the 28 URCAs in which pulsation was observed,11 showed a change in shape,while in 34 URCAs without visible pulsation,5 showed a change in shape.The aneurysms with detectable pulsation were more likely to show a change in shape (x2=4.891,P=0.027),with an odds ratio of 3.753.Conclusions URCAs with a large aspect ratio are easily to show the pulsation by ECG gated 4D-CTA.Besides,the aneurysms with visible pulsation are more likely to show a change in shape after follow-up,which suggests a higher risk of rupture.