Objective:To summarize the clinical and imaging presentations of the pontine tegmental cap dysplasia (PTCD).Methods:The clinical, high resolution CT(HRCT) and MRI materials of 4 patients with PTCD between August 2007 to December 2024 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 10 months to 16 years.Results:Of 4 PTCD patients, severe or profound severe hearing loss ( n=8 ears), developmental delay, hypotonia and severe facioplegia ( n=3 cases) were found. On HRCT, all of 4 cases were associated with temporal anomalies [including a narrow bony cochlear nerve canal ( n=8 ears), duplicated (each n=4 ears) or narrow ( n=1 ear) internal auditory canal, enlarged vestibular aqueduct ( n=2 ears), enlarged vestibules and dysplastic lateral semicircular canals ( n=3 ears), ossicular deformation( n=2 ears). The stenosis of the labyrinthine segments of the facial nerve canal ( n=3 ears) and facial nerve canal ectopia(n=6 ears)], atrial or ventricular septal defect (each n=1 case), thoracic or lumbar vertebral anomalies and ribs fusion ( n=3 cases). On the brain MRI, the variable flattening of the ventral pons and dysmorphism of the dorsal upper pons cap-like bulging and protruding in the fourth ventricle were shown in all cases, the vermian and cerebellar peduncles hypoplasia gave rise to a molar tooth appearance. The dysplastic ( n=3 ears), aplastic( n=5 ears) cochlear nerves and dysplastic facial nerves ( n=3 ears) were found. Conclusion:The PTCD patients usually present severe hearing loss, developmental delay, hypotonia, and facioplegia. The flattening of the ventral pons and the dorsal upper pons cap-like bulging usually with duplicated internal auditory canal and severe facial and auditory nerves dysplasia are its imaging features.

Objective:To evaluate the effect of cathepsin B(CTSB)/NOD-like receptor pyrin domain containing 3(NLRP3)pathway on the polarization of macrophages induced by LPS.Methods:The well-growing RAW264.7 mouse mononuclear macrophage lines were cultured in vitro and divided into 3 groups(n=6)according to the random number table method:control group(C group),LPS group(L group)and LPS+CA074-me(CTSB inhibitors)group(B group).C group was cultured normally for 24 h,L group was cultured with LPS concentration of 1 μg/ml medium for 24 h.B group was pretreated with CTSB inhibitor CA074-me 30 μmol/L for 1 h before LPS induction,and co-cultured with LPS concentration of 1 μg/ml medium for 24 h.After 24 hours,the morphological changes of the cells were observed by microscope,the concentrations of IL-1β and IL-18 in the supernatant were determined by ELISA.The ex-pressions of cathepsin B precursor(pro-CTSB),mature cathepsin B(mature-CTSB),NLRP3,apoptosis-related speck protein(ASC)and apoptosis-related speck protein-1(caspase-1)were detected by Western blot.The mRNA expression levels of CD32,inducible ni-tric oxide synthase(iNOS),arginase 1(Arg-1)and CD206 were detected by qRT-PCR.The positive expression rates of M1 macro-phage surface marker CD86 and M2 macrophage surface marker CD206 were detected by flow cytometry.Results:Compared with group C,the morphology of cells in groups L and B became larger and pseudopodia appeared.The concentrations of IL-1β and IL-18 in cell supernatant were increased,the expressions of pro-CTSB,mature-CTSB,NLRP3,ASC and caspase-1 were increased,and the expressions of CD32,iNOS mRNA were up-regulated and the positive rates of CD86 and CD206 were increased(P<0.01).Arg-1 and CD206 mRNA in group B were up-regulated(P<0.01).Compared with group L,the pseudopodia of group B were reduced,and the morphology was closer to group C.The concentration of IL-1β and IL-18 in the supernatant,the expression of mature-CTSB,NLRP3,ASC and caspase-1,CD32 and iNOS mRNA and the positive rate of CD86 were down-regulated in group B.The expression of pro-CTSB,Arg-1 and CD206 mRNA and the positive rate of CD206 were increased(P<0.01).Conclusion:Inhibition of CTSB/NLRP3 pathway can reduce the inflammatory response,reduce the LPS-induced polarization of RAW264.7 cells to M1 macrophages,and pro-mote their polarization to M2 macrophages.

Objective:To summarize the clinical and imaging presentations of the pontine tegmental cap dysplasia (PTCD).Methods:The clinical, high resolution CT(HRCT) and MRI materials of 4 patients with PTCD between August 2007 to December 2024 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 10 months to 16 years.Results:Of 4 PTCD patients, severe or profound severe hearing loss ( n=8 ears), developmental delay, hypotonia and severe facioplegia ( n=3 cases) were found. On HRCT, all of 4 cases were associated with temporal anomalies [including a narrow bony cochlear nerve canal ( n=8 ears), duplicated (each n=4 ears) or narrow ( n=1 ear) internal auditory canal, enlarged vestibular aqueduct ( n=2 ears), enlarged vestibules and dysplastic lateral semicircular canals ( n=3 ears), ossicular deformation( n=2 ears). The stenosis of the labyrinthine segments of the facial nerve canal ( n=3 ears) and facial nerve canal ectopia(n=6 ears)], atrial or ventricular septal defect (each n=1 case), thoracic or lumbar vertebral anomalies and ribs fusion ( n=3 cases). On the brain MRI, the variable flattening of the ventral pons and dysmorphism of the dorsal upper pons cap-like bulging and protruding in the fourth ventricle were shown in all cases, the vermian and cerebellar peduncles hypoplasia gave rise to a molar tooth appearance. The dysplastic ( n=3 ears), aplastic( n=5 ears) cochlear nerves and dysplastic facial nerves ( n=3 ears) were found. Conclusion:The PTCD patients usually present severe hearing loss, developmental delay, hypotonia, and facioplegia. The flattening of the ventral pons and the dorsal upper pons cap-like bulging usually with duplicated internal auditory canal and severe facial and auditory nerves dysplasia are its imaging features.

Objective To explore and construct the clinical questions and outcome indicators of the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome;To provide a basis for the subsequent preparation of this guide to form recommendations.Methods First,by searching the databases of seven major Chinese and English journals,including CNKI,the preliminary list of clinical problems and outcome indicators in the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome were sorted out,and then the clinical questions and outcome indicators that formed the recommendations of the guide were finally determined based on the modified Delphi method in the form of three rounds of online.The first two rounds were conducted in the form of online questionnaires filled out by experts,and the importance ratings of clinical issues and outcome indicators were imported into the SPSS 27.0 software for statistical analysis.The first and second rounds of clinical questions and outcome indicators were rated as the average score≥4,full score frequency≥30%,and the coefficient of variation≤25%,respectively;the inclusion criteria for entering the second round of evaluation were an average score of≥7 and an average score of≤25%.The third round would be further discussed and voted on by experts in an online consensus meeting,with a voting rate of≥80%as the standard to determine the final items to be included in the guidelines.Results A total of 109 questionnaires were distributed nationwide in the first round of inquiry,and 107 were collected;a total of 20 questionnaires were distributed for the second round of expert research,and 20 were collected.The positive coefficients of the first and second rounds of experts were 98.17%and 100%;the Cronbach coefficients of clinical questions were 0.937 and 0.943,respectively;the Cronbach coefficients of the outcome indicators were 0.970 and 0.940,respectively.In the third round,a total of 22 experts participated in the meeting and all voted,resulting in a positive coefficient of 100%and an authority coefficient of 0.88.13 clinical questions and 17 outcome indicators were finally included in Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome.Conclusion According to the results of the above three rounds of modified Delphi method,it indicates that the questionnaire survey in the process of formulating the guidelines is highly reliable,which can provide a reliable basis for the writing of this guide,and to provide a reference for the development of acupuncture guidelines in related fields.

Objective To construct a nomogram prediction model based on anti-cyclic citrullinated peptide antibody(anti-CCP an-tibody)and rheumatoid factor(RF)to predict the probability of cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods A total of 437 RA patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to February 2024 were selected as the study objects,the clinical data of the patients were collected,and they were divided into RA+CVD group(n=88)and RA group(n=349)according to the follow-up results.The risk factors of CVD in RA patients were screened by univariate and multivariate Logistic regression analysis,and the prediction model of CVD in RA patients was constructed and internally validated.Results Multivariate Logistic regression analysis showed that age,course of disease,uric acid,C-reactive protein,hyperten-sion and diabetes,anti-CCP antibody and RF were independent risk factors for CVD in RA patients(P＜0.05).The constructed mod-el was internally validated.The area under the area(AUC)of the training set and the validation set were 0.891(95％CI:0.851-0.930)and 0.867(95％CI:0.790-0.944).Conclusion The prediction model constructed in this paper has good predictive and dis-crimination ability,and has a high predictive value for whether RA patients are complicated with CVD.

Objective To evaluate the advantages of powder-liquid double-chamber bag products compared with traditional powder injection. Methods The systematic review method was used to collect the literature on powder-liquid double-chamber bag, extract common evaluation indicators, evaluate the use value of powder-liquid double-chamber bag products, and conduct a comprehensive comparison with traditional powder injection products. Results A total of 23 articles were included in the literature. The effectiveness indicators used for evaluation were the stability of the liquid medicine, the accuracy of the preparation concentration, and the residual amount of the liquid medicine; the safety indicators were the incidence of insoluble particles and the incidence of punctures and scratches. The economic indicators were preparation cost, occupied volume of preparation supplies, waste weight, hospitalization cost and incidence of blood infection. The applicability indicators were preparation time, average occupation of medical staff, packaging weight and storage and transportation volume, environmental adaptability, and ease of waste disposal. Accessibility indicators are the number of manufacturers, raw material supply capacity, and patient affordability. Through the evaluation of literature evidence, it was found that the stability and concentration accuracy of the powder-liquid double-chamber bag were higher than those of the traditional powder injection, and the domestic supply had been achieved. The double-chamber bag method can reduce the infusion reaction and shorten the preparation time of the liquid medicine. Conclusion Compared with traditional powder injectabler products, powder-liquid double-chamber bags have advantages in the dimensions of effectiveness, safety, economy, suitability and innovation, and the accessibility dimension meets the requirements.

Objective To explore the clinical significance and to investigate the expression of TOMM40L in the tis-sue of triple-negative breast cancer(TNBC).Methods The expression of TOMM40L in TNBC tissues and normal tissues was analyzed with TCGA and UALCAN databases.Univariate and multivariate Cox regression analysis and Nomogram model were used to evaluate the prognostic value of TOMM40L in TNBC patients.Furthermore,the ex-pression of TOMM40L in breast cancer cell lines was evaluated using Western blot analysis and quantitative real-time PCR.Specific siRNA knockdown was performed to evaluate the migration,and cell proliferation of TOMM40L.The potential signaling pathways of TOMM40L were identified by GO and KEGG and GSEA.Results TOMM40L was highly expressed in the TNBC compared to non-TNBC tumor tissues(P＜0.001).TOMM40L levels were en-hanced in TNBC cell lines as compared to other non-TNBC cell lines.CCK-8 and Transwell assay demonstrated that TOMM40L knockdown reduced the proliferation and migration of TNBCcell lines.Functional enrichment analysis showed that TOMM40L was involved in glucose metabolism-related pathways.Conclusions The expression of TOMM40L is increased in TNBC and is correlated with poor prognosis.TOMM40L may promote TNBC migration and proliferation.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

Objective:To evaluate the relationship between the mechanism of mild hypothermia-induced reduction of neuronal apoptosis during cerebral ischemia-reperfusion (I/R) and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in rats.Methods:Forty SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 5 groups ( n=8 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (IR group), hypothermia + cerebral I/R group (HIR group), hypothermia + cerebral ischemia-reperfusion + solvent group (HIR-DMSO group) and hypothermia + ischemia-reperfusion + CaMKK2 inhibitor STO-609 group (HIR-STO609 group). A global cerebral I/R injury model was established using the four-vessel occlusion method. In HIR group, HIR-DMSO group, and HIR-STO609 group, an ice blanket was used to reduce the body temperature immediately after cerebral ischemia, bringing the core body temperature down to 32.5-33.5 ℃, and rewarming was carried out 4 h later. One hour before developing the model, STO-609 solution 4 μl was injected into the lateral ventricle in HIR-STO609 group, and the equal volume of dimethyl sulfoxide solution was given instead in HIR-DMSO group. At the end of reperfusion, the modified neurological severity score (mNSS) was performed. Then the rats were sacrificed under deep anesthesia, and the hippocampal tissues were taken to observe the pathological results of the hippocampal tissues (using HE staining and Nissl staining) and to determine the apoptosis rate of neurons (by TUNEL method) and expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X (Bax), CaMKK2, phosphorylated AMPK (p-AMPK) and AMPK (by Western blot). Results:Compared with Sham group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, and the ratio of p-AMPK/AMPK was decreased in IR group ( P<0.05). Compared with IR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly decreased, the expression of Bax was down-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was up-regulated, and the ratio of p-AMPK/AMPK was increased in HIR group ( P<0.05). Compared with HIR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, the ratio of p-AMPK/AMPK was decreased ( P<0.05), and no significant change was found in the aforementioned parameters in HIR-DMSO group ( P>0.05). Conclusions:Mild hypothermia can inhibit neuronal apoptosis by up-regulating the CaMKK2/AMPK signaling pathway, thus reducing cerebral I/R injury in rats.

Objective:To evaluate the role of peptidylarginine deiminase 4 (PAD4)-mediated development of neutrophil extracellular traps (NETs) in lung ischemia-reperfusion injury (LIRI) in mice.Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=24 each) using a table of random numbers: sham operation group (group S), sham operation + PAD4 specific inhibitor GSK484 group (group S+ G), lung ischemia-reperfusion group (group L), and lung ischemia-reperfusion + GSK484 group (group L+ G). After anesthesia and mechanical ventilation, mice were subjected to left hilum occlusion for 1 h followed by 2 h of reperfusion to establish the LIRI model in L and L+ G groups. Mice underwent thoracotomy for 3 h without left hilum occlusion in S and S+ G groups. In S+ G and L+ G groups, GSK484 4 mg/kg was intraperitoneally injected once a day for 3 days before developing the model. At the end of reperfusion, blood samples were collected from the abdominal aorta for blood gas analysis to record arterial partial pressure of oxygen (PaO 2). Mice were then sacrificed to collect bronchoalveolar lavage fluid (BALF) and to obtain lung tissues. The concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in BALF were measured using enzyme-linked immunosorbent assay. The wet/dry lung weight (W/D) ratio was calculated. The lung tissues were obtained for microscopic examination of pathological changes (with a light microscope) which were scored after hematoxylin-eosin staining and for determination of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) (by colorimetric assay) and expression of PAD4, neutrophil elastase (NE), high-mobility group box 1 (HMGB1), and citrullinated histone 3 (Cit-H3) (by Western blot). Results:Compared with group S, lung injury scores and W/D ratios were significantly increased, PaO 2 was decreased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, the content of SOD was decreased, the content of MDA was increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was up-regulated in L and L+ G groups ( P<0.05), and no significant changes were observed in the aforementioned parameters in group S+ G ( P>0.05). Compared with group L, lung injury scores and W/D ratios were significantly decreased, PaO 2 was increased, concentrations of IL-1β, IL-6, TNF-α, and MPO in BALF were decreased, the content of SOD was increased, the content of MDA was decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group L+ G ( P<0.05). Conclusions:Up-regulated PAD4 expression can promote the development of NETs and aggravate oxidative stress and inflammatory responses in lung tissues, thereby participating in LIRI in mice.