Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P＜0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P＜0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P＜0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P＜0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P＜0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.

OBJECTIVE To analyze the narrow-band imaging(NBI)endoscopic characteristics of recurrent early glottic carcinoma patients after undergoing CO2 laser surgery with a suspend laryngoscopy.METHODS A retrospective study was conducted on patients with early-stage glottic carcinoma(Ⅰ-Ⅱ stage)who received CO2 laser surgery under supportive laryngoscopy at the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2017 to December 2023.The medical history,treatment methods,laryngoscopy(including common white light endoscopy and NBI endoscopy),imaging examinations,and pathological results of patients with recurrent glottic carcinoma were collected at different time points including preoperation,postoperative 1 month,postoperative 3 months,and postoperative 6 months.The endoscopic characteristics of NBI in patients with recurrent glottic carcinoma were summarized.RESULTS First,among 18 patients with early-stage glottic cancer recurrence after CO2 laser,the diagnostic rate of NBI endoscopy for laryngeal cancer recurrence(88.89％,16/18)was significantly higher than that of common white light endoscopy(55.56％,10/18)(χ2=4.985,P=0.026).The intraepithelial papillary capillary loop(IPCL)was classified as a vertical vessel according to ELS in all relapsed patients.However,according to Ni classification,the IPCL of the 72.22％(13/18)were classified as type V,while the IPCL of 27.78％(5/18)showed suspicious abnormal neovascularization(punctate or dilated and curved).The proportion of patients with abnormal IPCL on the surgical surface at 1 month,3 months,and 6 months postoperatively was 0.00％,27.78％(5/18),and 61.11％(11/18),respectively,with statistically significant differences(χ2=16.164,P<0.001),which indicated that the longer the follow-up time for recurrent laryngeal cancer patients,the higher the proportion of patients with abnormal IPCL on the surface of the surgical area under NBI endoscopy.CONCLUSION For early glottic carcinoma after CO2 laser surgery with a suspend laryngoscopy,the appearance of suspicious new blood vessels with type Ⅴ IPCL and punctate or dilated curvature under NBI endoscopy may indicate early recurrence of laryngeal cancer.

OBJECTIVE To analyze the changes of temporary abnormal intraepithelial papillary capillary loop(IPCL)in the surgical area of early glottic laryngeal cancer after CO2 laser resection.METHODS A retrospective study was conducted on early-stage glottic carcinoma patients who visited the Department of Otolaryngology,Head and Neck Surgery at the Second Affiliated Hospital from January 2017 to November 2023.Patients who underwent CO2 laser surgery accepted electronic laryngoscopy examination at 1 month,3 months,and 6 months postoperatively(including white light endoscopy and narrowband imaging endoscopy(NBI),and their medical history,treatment methods,laryngoscopy images,imaging data,and pathological results before and after treatment were systematically collected.The changes in laryngoscopy characteristics at different follow-up times after surgery were analyzed.RESULTS This study included 55 patients with non recurrent early glottic carcinoma who underwent CO2 laser surgery.At 1 month,3 months,and 6 months after surgery,there were significant differences in the proportion of patients with pseudomembrane coverage(72.73%vs.25.45%vs.7.27%),granulation formation(60.00%vs.34.55%vs.1.82%),and abnormal IPCL(23.64%vs.7.27%vs.0.00%)on the surface of the surgical area(P<0.001),and abnormal IPCL(mainly type Va and Vb)can be observed under NBI endoscopy from 1 month to 3 months after surgery.Within 6 months after surgery,the pseudomembrane detachment,granulation regression,scar formation,and abnormal IPCL in the surgical area disappeared.CONCLUSION Early glottic carcinoma patients may experience temporary abnormal IPCL within 3 months after receiving CO2 laser resection,but the abnormal IPCL could disappear within 6 months after surgery for some patients.Therefore,close observation is necessary within 6 months after surgery and there is no need for urgent biopsy.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To explore the risk factors for central venous catheter (CVC) dysfunction in hemodialysis patients, construct a risk prediction model, and verify the model's predictive performance.Methods:The retrospective research method was adopted. From January 2021 to August 2023, convenience sampling was used to select 442 patients who underwent hemodialysis by CVC at the First Hospital of Shanxi Medical University, Shanxi Provincial People's Hospital, and Shanxi Bethune Hospital as the study subjects. Patients were divided into a modeling group ( n=309) and a validation group ( n=133) according to the order of time of CVC. The modeling group was divided into groups based on whether patients experienced catheter dysfunction. Multivariate Logistic regression was used to analyze the influencing factors of hemodialysis catheter dysfunction and construct a nomogram model. The model's predictive performance was evaluated using the calibration curve, area under the receiver operating characteristic curve ( AUC), and the Hosmer Lemeshow goodness of fit test. Results:Multivariate Logistic regression analysis showed that history of thrombosis, blood hypercoagulability, catheterization site, catheter-related infection, and catheterization duration were influencing factors for catheter dysfunction in hemodialysis ( OR=5.119, 5.174, 6.362, 2.913, and 5.353; all P<0.05). The above five factors were used as independent variables to construct a nomogram. Internal validation of the model showed that the Hosmer Lemeshow test was χ 2=10.828, P=0.212, and AUC was 0.837 [95% confidence interval (0.781, 0.893) ], and the calibration curve fitted well with the ideal curve. External validation of the model indicated that the Hosmer Lemeshow test was χ 2=1.944, P=0.925, and AUC was 0.825 [95% confidence interval (0.744, 0.906) ], and the calibration curve almost coincided with the ideal curve. Conclusions:The constructed nomogram can predict the risk of catheter dysfunction in hemodialysis patients and provide a reference for nursing staff to develop corresponding interventions.

Objective To compare the safety and clinical value of warm-water infusion or carbon dioxide(CO2)insufflation in difficult colonoscopy.Methods A collection of 150 patients from May 2021 to October 2023 who underwent unsedated and difficult colonoscopy were randomly divided into warm-water insufflation group(W group,n=50),CO2 insufflation group(C group,n=50)and air insufflation group(A group,n=50).Record the cecal insertion time,the abdominal pain score during the examination and 20 min and 1 h after the examination,the success rate of intubation,the polyps detection rate,the willingness to re-examine and the need for assistance in the three groups.Some patients were randomly selected to record partial pressure of end-tidal carbon dioxide(PetCO2)of pre-examination,the ileocecal and 20 min after the examination to understand CO2 retention in the body.Results The cecal insertion time of group A was longer than that of group W and group C,and group W was shorter than group C.The abdominal pain score of group A was higher than that of group W and group C at each time point,and the abdominal pain score during the examination was lower in the group W compared with group C.The success rate of intubation and the willingness to re-examination in the group A were lower than those in group W and group C,The above differences were statistically significant(P<0.05).However,there was no statistical difference between the the group W and group C in terms of success rate of intubation,willingness to re-examine,and abdominal pain score at 20 minutes and 1 hour after the examination(P>0.05).In the group W,significantly fewer patients required abdominal compression compared with the other two groups,and the rate of position conversion was significantly lower than that in group A(P<0.05).There was no significant difference in the detection rate of polyps among the three groups(P>0.05).In addition,PetCO2 of group C was within the normal range at all time points,and there was no statistical difference compared with the group A(P>0.05).Conclusion Compared with the air group,water or CO2 insufflation colonoscopy is safe and has a high success rate in difficult colonoscopy.It can reduce the patient's abdominal discomfort,especially water insufflation colonoscopy is more suitable for promotion in primary hospitals.

Objective:To develop a risk assessment scale for infusion port occlusion in patients with malignant tumors and to test its reliability and validity.Methods:An initial item pool was constructed based on literature review. Through purposive sampling, two rounds of Delphi consultations with 20 experts were conducted from March to May 2023. Weights were assigned to the indicators using the analytic hierarchy process (AHP), and the risk assessment scale was finalized. From June to September 2023, a convenience sample of 278 malignant tumor patients with infusion ports from four Class Ⅲ Grade A hospitals in Shanxi Province was selected for item analysis and reliability and validity testing.Results:The risk assessment scale for infusion port occlusion in malignant tumor patients includes five dimensions, 16 primary indicators, and 35 secondary indicators. The content validity index at the scale level was 0.925, and at the item level ranged from 0.818 to 1.000. A total of five factors were extracted by exploratory factor analysis, with a cumulative contribution rate of 57.081% to the variance. The area under the receiver operating characteristic curve was 0.815, with a cutoff score of 24.50. The overall Cronbach's α coefficient was 0.910, and the split-half reliability coefficient was 0.762.Conclusions:The risk assessment scale for infusion port occlusion in malignant tumor patients demonstrates good reliability and validity, and has high predictive power, which provides a scientific basis for identifying high-risk populations in clinical settings.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH₂-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.