Purpose To investigate the cell components in different tumor lineages of multiple synchronous pituitary neuro-endocrine tumors(PitNETs)/neuroendocrine tumors(MSPs)and to carry out accurate histological typing,which provides an important basis for determining the follow-up plan and adjuvant therapy after surgery.Methods The clinical data of 855 pa-tients with PitNETs were collected and reclassified according to the new WHO standard.The clinicopathological features of 13 patients diagnosed as MSPs were analyzed retrospectively.The immunohistochemical EnVision two-step method was used to de-tect the expression of PIT-1,SF-1,T-PIT,GH,PRL,TSH,LH,FSH,ACTH,etc.,and related literatures were reviewed.Methods A total of 855 cases of pituitary neuroendocrine tumor from the second hospital of the Chinese Hebei Medical U-niversity were collected and reclassified according to the new WHO standard,and review the literature.Results(1)The age of patients were 39-68 years with median age of 55 years.7 cases were female and 6 were male;(2)Imaging findings:There was 1.2～3.8 cm(mean 2.5 cm)in maximum tumor di-ameter.13 patients were large adenomas,neither MSPs nor sin-gle lineage PitNETs could not assessed on imaging;(3)Clinical manifestations:3 cases had hyperprolactinemia which all contai-ning PitNETs components of PRL,one case was immature PIT-1 polyhormone cell tumor,one was dense granular prolactinoma,and one case was eosinophilic stem tumor.One patient had Cushing's disease and contained a Crook cell tumor component;two had elevated ACTH,and one had an adrenocorticotropic ad-enomatous component.In the two patients with no evidence of hormone excess,all contained gonadotropin cell tumor compo-nents;(4)Combination form:11 cases of the combination of the two cell lineages(5 cases of combination of SF-1 lineage and PIT-1 lineage;4 cases of combination of T-PIT lineage and PIT-1 lineage;1 case of null cell tumor and PIT-1 lineage;1 case of plurihormonal PitNETs and SF-1 lineage);Two cases of three cell combinations(null cell tumor,PIT-1 lineage,and T-PIT lineage);Among them,13 cases were PIT-1 lineage tumors,46.2％(6/13)were gonadotropin cell tumor,38.5％(5/13)were prolactinoma;(5)The presence of high-risk lineage tumors in the 10 patient combinations:3 immature PIT-1-lineage tumor,1 Crooke cell PitNETs,1 acidophil stem cells tumor,3 zero-cell PitNETs,and 4 silent-type sparse granular adrenocorti-cotropic hormone PitNETs;Two of them were combinations of two high-risk subtypes.Conclusion MSPs in our center are large adenomas,although their incidence is only 1.5％of Pit-NETs,2/3 cases have high-risk lineage tumor components,and the use of pituitary cell lineage transcription factors and adeno-hypophyseal hormones plays an important role in distinguishing and clarifying the different components of MSPs.

Objective:To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma.Methods:Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed.Results:There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients′ median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated.Conclusions:Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Objective:To explore mechanism of Chaihu Longgu Muli Decoction and Ganmai Dazao Decoction in treatment of post-stroke depression(PSD)based on network pharmacology,molecular docking and animal experiment.Methods:TCMSP and other databases were used to predict active components and targets of Chaihu Longgu Muli Decoction and Ganmai Dazao Decoction.Targets of PSD were retrieved from PharmGKB and other databases,and"component-intersection target-disease"network was constructed by Cytoscape(v3.9.1)software.PPI network was constructed by String(v11.5)database,and GO enrichment and KEGG pathway analy-sis of intersection targets were performed by DAVID6.8 database.AutoDock vina(v1.1.2)software was used for molecular docking.Pymol(v 2.5)and other softwares were used to visualize optimal docking results.Animal experiments were setup in control group,model group,fluoxetine group,TCM group and TCM+fluoxetine group,neurobehavioral scores and expressions of neurotransmitters and inflammatory factors in brain tissues were detected.mRNA and protein expressions of key genes PPARG,MAPK3,AKT1,PIK3CA were detected by RT-qPCR and Western blot.Results:A total of 225 kinds of active ingredients of Chaihu Longgu Muli Decoction and Ganmai Dazao Decoction were obtained,which acted on 119 targets of PSD,among which key targets included MAPK3,AKT1,PIK3CA and PPARG,key pathways including MAPK signaling pathway,PI3K-Akt signaling pathway and etc.Compared with model group,MAPK3 mRNA and protein expressions were decreased,AKT1,PIK3CA,PPARG mRNA and protein expressions were increased in TCM group and TCM+fluoxetine group(P<0.05).Conclusion:Mechanism of Chaihu Longgu Muli Decoction and Ganmai Dazao Decoction in treatment of PSD may be related to inhibition of MAPK3 expression,promotion of AKT1,PIK3CA,PPARG expressions,alleviation of inflammatory response and oxidative stress in brain tissues.

Objective:The purpose of this study is to test and assess the model of modeling data of TaiChi accelerator in the Raystation Treatment Planning System(RayStation system)according to the test method and item of TG119 report of American Association Physicians Medicine(AAPM).Methods:The intensity-modulated radiation therapy(IMRT)and volumetric-modulated arc therapy(VMAT)plans of the test cases of different clinical situations,which included the simulated multi target region,prostate target region,head and neck target region,easy type C-shape target region plan and difficult type C-shape target region plan,were designed according to the AAPM TG119 report in the treatment planning system.The deviations of the doses of point and area of the two kinds of plans were measured,and the measured results were compared and analyzed with the recommended standards of AAPM TG119 report.The IBA CC13 ionization chamber and the ArcCHECK matrix ionization chamber were used respectively to verify the point dose and area dose,and the assessment standard was γ passing rate under 3%3mm.The confidence interval was adopted to judge the consistency between the measured dose and the calculated dose.Results:The accuracies of plan dose target,point dose deviation and area dose distribution of tested cases could meet the requirement of the TGl19 report.The deviations of mean doses for the high-dose points of IMRT plan and VMAT plan of tested cases were respectively(0.39±1.02)%and(1.27±0.64)%,and the confidence intervals of them were respectively 2.39%and 2.52%.The average dose deviations of low doses of organ at risk(OAR)of IMRT plan and VMAT plan were respectively(0.53±1.73)%and(0.88±1.11)%,and the confidence intervals were respectively 3.92%and 3.06%.The average γ passing rate under 3%/3mm of IMRT plan and VMAT plan were respectively(99.52±0.366)%and(99.86±0.136)%,and the confidence intervals of them were respectively 1.196%and 0.406%.Conclusion:The TaiChi accelerator performance and the accuracy of Raystation system 6MV FFF model fitting can meet the standard of TG119 report,and the subsequent standards of the quality control of equipment and patients were established according to these tested results,which would provide reference for the improvement of the performance of subsequent accelerator.

Objective:To analyze and evaluate the application effect of magnetic navigation-guided nasojejunal tube placement in critically ill patients by literature retrieval.Methods:The Chinese databases of CNKI,Wanfang,VIP and Chinese Biomedical Literature Service System were searched,as well as the literature on randomized controlled trials of magneto-guided nasojejunal tube placement in critically ill patients in foreign language databases of PubMed,CINAHL,Cochrane Library,Web of Science,and Embase,the search period was from January 2000 to September 2023.The literature were screened according to the inclusion and exclusion criteria,and the quality of the literature was evaluated.RevMan 5.4.1 software was used to conduct a meta-analysis of the four outcomes in the literature:success rate of placement,time required for successful placement,time to recovery of vital signs,and patient satisfaction.Results:A total of 7 randomized controlled trials of 7 studies were included,including 4 Chinese studies and 3 English studies,involving 682 patients.The success rate of magnetic navigation-guided nasojejunal tube placement was higher than that of bedside blind nasojejunal tube placement,the difference was statistically significant[OR=4.78,95%CI(2.16～10.58),P<0.0001].The time required for magnetic navigation guided nasojejunal tube placement was less than that of the bedside blind nasojejunal tube placemen,the difference was statistically significant[MD=-12.91,95%CI(-22.93～-2.90,P<0.00001].The time required for recovery of vital signs in patients with magnetic navigation guided nasojejunal tube placement was less than that of the bedside blind nasojejunal tube placemen,the difference was statistically significant[MD=-9.11,95%CI(-12.09～-6.13,P<0.00001].The satisfaction of patients with the magnetic navigation-guided nasojejunal tube placement was higher than that of patients with the bedside blind nasojejunal tube placement,the difference was statistically significant[OR=11.61,95%CI(3.96～34.01),P<0.00001].Conclusion:Compared with bedside blind nasojejunal tube placement,magnetic navigation-guided nasojejunal tube placement can significantly improve the success rate of nasojejunal tube placement in critically ill patients,reduce the time required for successful nasojejunal tube placement,reduce the recovery time of patients'vital signs,and improve patient satisfaction.

【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI).Methods:A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis.Results:During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH 2O, 1 cmH 2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH 2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH 2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ 2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. Conclusion:Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Objective:To investigate the effects of early applying of basic fibroblast growth factor (bFGF) on corneal haze formation after surface ablation surgery in rabbits.Methods:The right eyes of 60 healthy New Zealand white rabbits received photorefractive keratectomy (PRK) and were randomized into PRK+ normal saline group, PRK+ bFGF group and simple PRK group, with 20 rabbits in each group.Normal saline solution and bFGF were topically administered according to grouping, respectively, 3 times per day, 1 drop for each time until the sacrifice of the animals, and no drug was used in the PRK group.Another 8 normal rabbits were served as blank control group.The corneal healing response and haze formation were evaluated by anterior segment photography and anterior segment optical coherence tomography (AS-OCT) and graded based on Fantes criteria.Corneal histopathology was examined by hematoxylin-eosin staining.Immunohistochemistry was used to detect the expression of transforming growth factor-β 1(TGF-β 1), α-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2) in cornea.This study protocol was approved by the Experimental Animal Ethic Committee of Affiliated Hospital of Binzhou Medical University (20180209-03). The use and care of the animals complied with the Statement of ARVO. Results:The corneal epithelium was completely healed in 3-4 days following surgery and there was not significantly different in healing time among the three groups.( F=0.57, P=0.57). The haze grading was significantly different among different groups at different time points ( Fgroup=41.736, P<0.01; Ftime=129.445, P<0.01) and showed the highest score in the PRK+ bFGF group on the 28th day after operation.On the 7th day after surgery, AS-OCT image showed that the surface reflection of corneal epithelium was continuous and smooth and corneal epithelium was not tightly attached to the superficial stromal layer; the reflection of the superficial stromal layer was enhanced in all the operation groups.The proliferation of corneal epithelial cells and superficial stromal layer in the operation area were seen under the optical microscope, and the arrangement of collagen fibers in the stromal layer was disordered with the most obvious changes in the PRK+ bFGF group in comparison with the PRK+ normal saline group and the simple PRK group, and these findings became worse on postoperative 28 days.The corneal epithelial surface reflection in the blank control group was continuous and smooth.Immunohistochemistry showed that a few MMP-2 positive cells were seen in the blank control group.TGF-β 1, α-SMA and MMP-2 proteins were positively expressed in the corneas 7 days after surgery in the three groups, and their expressions were the most obvious in the PRK+ bFGF in comparison with the PRK+ normal saline group and the PRK group and were enhanced 28 days after operation, showing statistically differences (all at P<0.05). Conclusions:Early application of bFGF following surface ablation surgery promotes the proliferation of corneal epithelial cells and irregular arrangement of collagen in the superficial stromal layer, which is associated with the expressions of haze-related factors TGF-β 1, α-SMA and MMP-2 in corneas.

Objective To study the relationship of serum 25-hydroxy vitamin D [25-(OH) D] and vitamin D binding protein (DBP) in premature infants with bronchopulmonary dysplasia (BPD) and their clinical significance.Method From March 2017 to September 2018,the premature infants with gestational age (GA)＜32 weeks admitted to the neonatal department of our hospital were prospectively studied.All the premature infants were given 800 IU/d vitamin D supplement from one week after birth.Venous blood sample were collected at birth and 28 d after birth to measure 25-(OH) D aud DBP levels.The infants were evaluated for BPD at 28 d after birth and then assigned into the BPD group and the non-BPD group.The differences of 25-(OH) D and DBP levels were compared.Result A total of 170 premature infants (GA＜32 weeks) were included,including 56 cases in the BPD group and 114 cases in the non-BPD group.The BPD group had 34 males,the GA was (29.8±1.2) weeks,the birth weight (BW) was (1 198± 157) g.The non-BPD group had 95 males,the GA was (30.2± 1.5) weeks,the BW was (1 243± 146) g.No significant differences existed in GA,BW and male gender proportion between BPD group and non-BPD group (P＞0.05).The BPD group had a lower levels of serum 25-(OH) D at birth [(27.8±5.9) nmol/L vs.(30.4±1.1) nmol/L,P＜0.05].The levels of serum 25-(OH) D in moderate/severe BPD group were significantly lower than mild BPD group [(25.3±4.9) nmol/L vs.(29.7±5.9) nmol/L,P＜0.05];25-(OH) D in BPD group was still lower than the non-BPD group at 28 days after birth (after vitamin D supplement) [(77.5±11.7) nmol/L vs.(83.8±11.6) nmol/L,P＜0.05].Comparison of serum DBP levels between the two groups showed that,DBP at 28 d after birth in BPD group were significantly lower than the non-BPD group,and DBP in moderate/severe BPD group were significantly lower than the mild BPD group [(373.9± 19.1) μg/ml vs.(391.4±23.6) μg/ml],the differences were both statistically significant (P＜0.05).Multivariate analysis showed that the high serum 25-(OH)D level at birth (OR=0.827,95％CI0.693～0.987) was protective factors for BPD,while neonatal pneumonia (OR=4.331,95％CI 1.269～14.784) and neonatal sepsis (OR=4.020,95％CI 1.153～14.015) were risk factors for BPD.Conclusion The high serum 25-(OH) D level at birth in preterm infants was protective factors for BPD,while neonatal pneumonia and sepsis were the risk factors for BPD.Moreover,low serum 25-(OH) D level at birth and low serum DBP level at 28 d after birth maybe useful indicators for the severity of BPD.