ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

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Objective To investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.

Objective To investigate the imaging features of papillary tumor of the pineal region(PTPR).Methods The ima-ging data of 10 patients with PTPR confirmed by operation and pathology were analyzed retrospectively.Results All lesions were located in the posterior commissure area of the posterior inferior wall of the third ventricle.All lesions were heterogeneously hyper-intensity on T1WI and hyperintensity on T2WI.Multiple small cysts or microcapsules signal intensity were observed within the tumor.Of all 10 lesions,there were 9 lesions with high signal intensity within or at the edge of the lesion on T1WI.All lesions showed restricted diffusion.All 10 cases showed uneven and obvious enhancement patterns.Midbrain tectum was compressed and moved backward in 5 cases,moved downward in 2 cases,moved forward and downward in 1 case,and was not clearly displayed in other 2 cases.One case was disseminated and 1 case was hyperperfusion.There were all 10 cases with obstructive hydrocephalus and equal or slightly high density on CT imaging,and 4 cases with calcification.Conclusion Imaging characteristics of PTPR included the lesions centered on the posterior commissure,compressed tectum with backward and downward,multiple small cysts or micro-capsules components within the tumor,hyperintensity on T1WI,and uneven and obvious enhancement patterns.

BACKGROUND:In recent years,the treatment method of injecting bone cement into the intervertebral space has been introduced from abroad for the treatment of lumbar recurrent pain caused by lumbar disc degeneration and intervertebral space narrowing;however,some patients had vertebral fractures after treatment;the fracture may occur because the bone cement injected into the intervertebral space has a poor elastic modulus. OBJECTIVE:To analyze the effect of bone cement with different elastic moduli injected into the intervertebral space on the maximum stress of upper and lower vertebrae using a three-dimensional finite element model. METHODS:A volunteer with normal spine was recruited to obtain CT data.The finite element model of L2-L5 lumbar spine was established using Mimics,Geomagic,SolidWorks,and Ansys.Subsequently,a L3-L4 intervertebral space injection model with different doses(1 mL and 4 mL)of bone cement was established.Four different elastic moduli(1 000,2 000,4 000,and 8 000 MPa)were assigned to bone cement at each dose.Pressure and bending moment were applied on the surface of the L2 vertebral body to analyze the stress on the lower surface of the L3 vertebral body and the upper surface of the L4 vertebral body. RESULTS AND CONCLUSION:(1)In the case of the same amount of bone cement injection,as the elastic modulus of bone cement increased,the stress on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body increased.Among them,the bone cement with an elastic modulus of 1 000 MPa had the least effect on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body.Bone cement with elastic modulus of 8 000 MPa had the greatest effect on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body.Bone cement with different elastic moduli had little effect on the motion range of the whole lumbar spine.(2)The results indicate that injecting bone cement with lower elastic modulus while meeting treatment requirements can reduce the risk of postoperative fractures.

Objective To explore the clinical effect of neurointervention assisted alteplase thrombolysis in the treatment of acute ischemic stroke(AIS).Methods A total of 104 AIS patients admitted to Beijing Shunyi Hospital from June 2022 to June 2023 were selected as the research subjects,and they were divided into observation group and control group according to the treatment method,with 52 cases in each group.The patients in the control group were treated with alteplase thrombolysis,and the patients in the observation group were treated with neurointervention assisted alteplase thrombolysis.The therapeutic effect of patients in the two groups was evaluated according to the National Institutes of Health stroke scale(NIHSS)score at two weeks after treatment.Before treatment and 3,7 days after treatment,the serum nerve growth factor(NGF),neuron specific enolase(NSE),central nervous system specific protein S100β levels of patients in the two groups were detected by enzyme-linked immunosorbent assay;the peak systolic velocities of common carotid artery,basilar artery and vertebral artery of patients in the two groups were detected by ultrasound transcranial Doppler blood analyzer;the degree of neurological damage of patients in the two groups was evaluated by NIHSS scores.The occurrence of drug-related adverse reactions during treatment of patients in the two groups were recorded;the comprehensive living ability of patients in the two groups was evaluated by improved Rankin score at three months after treatment.Results The total effective rates of patients in the control group and the observation group were 80.77％(42/52)and 96.15％(50/52),respectively;the total effective rate of patients in the observation group was significantly higher than that in the control group(x2=6.029,P＜0.05).There was no significant difference in the serum NGF,NSE,S100β levels of patients between the two groups before treatment(P＞0.05).Compared with before treatment,the serum NGF level of patients in the two groups increased,and the serum NSE,S100β levels decreased at 3,7 days after treatment(P＜0.05).At 3,7 days after treatment,the serum NGF level of patients in the observation group was significantly higher than that in the control group,and the serum NSE,S100β levels were significantly lower than those in the control group(P＜0.05).There was no significant difference in the peak systolic velocities of common carotid artery,basilar artery and vertebral artery of patients between the two groups before treatment(P＞0.05).The peak systolic velocities of common carotid artery,basilar arteryand vertebral artery of patients at 3,7 days after treatment were significantly lower than those before treatment in the two groups(P＜0.05).After 3,7 days after treatment,the peak systolic velocities of common artery,basilar artery,and vertebral artery of patients in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in NIHSS score of patients between the two groups before treatment(P＞0.05).The NIHSS score of patients at 3,7 days after treatment was significantly lower than that before treatment in the two groups(P＜0.05).At 3,7 days after treatment,the NIHSS score of patients in the observation group was significantly lower than that in the control group(P＜0.05).The total incidence of adverse reactions of patients during treatment in the control group and observation group was 7.69％(4/52)and 9.62％(5/52),respectively;there was no significant difference in the total incidence of adverse reactions during treatment of patients between the two groups(x2=0.000,P＞0.05).At 3 months after treatment,the comprehensive living ability of patients in the observation group was better than that in the control group(P＜0.05).Conclusion Neurointer-vention assisted with alteplase thrombolysis in the treatment of AIS patients can significantly improve the treatment efficacy and the expression of neurolin,reduce the degree of neurological impairment and improve comprehensive living ability,and has a certain degree of safety.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Objective:To evaluate the clinical value of a capillary electrophoresis-based method for gene diagnosis of hyperphenylalaninemia.Methods:In this single-center prospective study, 40 newborns with suspected hyperphenylalaninemia detected by neonatal liquid chromatography-tandem mass spectrometry screening at Nanjing Maternity and Child Health Care Hospital from February 2021 to February 2023 were included, with 22 males, 18 females and a mean age at diagnosis of 21.93 days.Capillary electrophoresis was used to detect 85 variants of the phenylalanine hydroxylase ( PAH) gene in 40 newborns with suspected hyperphenylalaninemia.The PAH gene of undiagnosed patients was further analyzed by Sanger sequencing.The detection rate, sensitivity and specificity of capillary electrophoresis were calculated. Results:Among these 40 newborns with suspected hyperphenylalaninemia, 71 PAH variants were detected by capillary electrophoresis, 32 patients were clearly diagnosed, only 1 pathogenic variant was found in 5 patients, and no pathogenic variant was found in the last 3 patients.Therefore, the detection rate, sensitivity and specificity of capillary electrophoresis for analysis of the PAH gene were 80.00%, 88.75% and 100%, respectively. Conclusions:The capillary electrophoresis-based method can rapidly, efficiently and accurately detect PAH gene variants at lower cost and is a promising gene detection method for hyperphenylalaninemia in clinical practice.

Purpose To establish and evaluate a high-speed fragment-induced penetrating liver injury model in pigs assisted by portable ultrasound.Materials and Methods With the aid of portable ultrasound,the lower edge of the liver at the end of expiration and the lower edge of the right chest at the end of inspiration of 10 Landrace pigs were positioned on the body surface.Then the sighting line was traced to determine the direction of projection and the sighting point.High-speed(about 627 m/s)fragments were projected through an experimental ballistic gun to induce penetrating liver injury.Blood pressure,heart rate,respiratory rate,pulse oxygen saturation and other physiological indexes were measured 15 minutes before shooting and 20 minutes after shooting.20 minutes after injury,the liver injury and the degree of injury were examined by ultrasound.After injury,the liver injury and abdominal fluid accumulation were observed by on-site portable ultrasound,and the size of liver trauma,liver injury grade,abdominal fluid accumulation location and maximum depth were recorded.The degree of liver injury was evaluated by comparison with the gross pathological results.Results Nine out of ten pigs were successfully modeled.The success rate of penetrating liver injury induced by fragments was 90%(9/10),other organ injury in abdominal cavity was 22.22%(2/9),and diaphragm penetrating injury was 22.22%(2/9),which did not occur obvious hemopneumothorax.After injury,the systolic blood pressure,diastolic blood pressure,and pulse oxygen saturation of the pigs decreased[(132.44±12.65)mmHg vs.(103.33±33.43)mmHg,(96.44±12.27)mmHg vs.(70.89±24.21)mmHg,(89.44±8.49)%vs.(76.00±13.41)%;t=2.440,2.651,4.084,all P<0.05],and the heart rate increased[(94.00±17.39)times/min vs.(139.89±37.21)times/min;t=3.534,P<0.05].Within 20 minutes after modeling,portable ultrasound images showed that the liver injury was a patchy,heterogeneous,slightly strong echo area with clear and irregular boundary,and the continuity of the local liver capsule was interrupted.The ascites appeared in the abdominal cavity with the maximum depth of(4.16±1.35)cm.The American association for the surgery of trauma(AAST)liver injury grading of gross pathology after the animals were killed showed that there were 6 cases of grade Ⅱ and 3 cases of grade Ⅲ.Along the fragment projection direction,the short diameter measured by ultrasound was positively correlated with the depth of gross pathological laceration(r=0.945,P<0.001).Compared with the gross specimen,the accuracy rate of ultrasonic AAST grading of liver injury was 88.89%(8/9).Conclusion The model of high-speed fragment-induced liver injury in pigs assisted by portable ultrasound is accurate and stable,and portable ultrasound can effectively evaluate the penetrating liver injury,which provides a basis for the treatment of liver firearm injury.