Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

BACKGROUND:The thin alveolar bone in the lower anterior region increases the risk of labial bone resorption when intruding the teeth with clear aligners.The effect of sagittal overcorrection design on the labiolingual control of mandibular anterior teeth intrusion has not been fully investigated. OBJECTIVE:To explore the effect of overcorrection on the changes in the displacement and stress of the mandibular anterior teeth,especially the cervical and apical regions. METHODS:Through a male volunteer cone-beam CT data,the three-dimensional reconstruction of the mandible and teeth was conducted in the MIMICS and GEOMAGIC software.Moreover,the models of periodontal ligaments,attachments,and appliances were created in the SOLIDWORKS software.First,the study was divided into canine intrusion group and incisor intrusion group.Then,the overcorrection(0°,1°,2°)was designed on the bilateral mandibular central and lateral incisors.A total of six models were established.The models were assembled and imported into the ANSYS software to analyze and calculate the displacement and stress level. RESULTS AND CONCLUSION:(1)In the canine intrusion group,canines intruded and tipped lingually while incisors extruded and tipped lingually.In the incisor intrusion group,canines extruded and tipped lingually while incisors intruded and tipped lingually.(2)Without overcorrection,the incisors necks moved lingually while apexes moved labially.With overcorrection,the incisors tended to be upright,followed by labial tilt.The least cervical and apical displacements were detected under 1° overcorrection.(3)With overcorrection,the incisal cervical stress concentration area shifted from labial to lingual in the canine intrusion group,whereas the stress concentration area shifted from lingual to labial in the incisor intrusion group.(4)The incisors tended to tilt lingually when intruding the mandibular anterior teeth with clear aligners.The sagittal overcorrection design was conductive to maintain the stable position of incisors.However,the amount of overcorrection should be moderate.Excessive overcorrection might increase the labial inclination tendencies of incisors.

Fengweiqi is the whole plant of Rhodiola dumulosa.It is a kind of natural and precious folk medicinal plant,mainly distributed on hillside rocks and crevasses at the altitude of 1 600-4 100 m.Fengweiqi mainly contains flavonoids,volatile oil,polysaccharides,various amino acids and trace elements.Modern pharmacological studies have shown that Fengweiqi has many significant pharmacological activities,such as anti-oxidation,anti-fatigue,anti-hypoxia and bacteriostasis.In this paper,the textual research,chemical constituents,pharmacological actions and artificial cultivation of Fengweiqi were reviewed in order to provide reference for further research and development of Fengweiqi resources.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.

Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.