The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

Objective To develop and validate a model to predict the risk of radiation-induced lung injury (RILI) and assess its clinical feasibility. Methods Clinical data from 125 patients with non-small cell lung cancer (NSCLC) were included in the study. The patients were divided into training group (88 cases) and validation group (38 cases). Key predictive factors were identified using univariate and multivariate logistic regression analyses combined with least absolute shrinkage and selection operator (LASSO) regression. A predictive model was constructed and evaluated using a nomogram, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results The key variables identified by the model were tumor volume (P = 0.017), Eastern Cooperative Oncology Group performance status score (P = 0.035), 95% of the minimum dose to the target volume (P = 0.028), percentage of bilateral lung volume receiving 20 Gy of radiation (P < 0.001), and neutrophil-to-lymphocyte ratio (P = 0.021). The ROC curve showed that the areas under the curve (AUC) for the model in the training and validation groups were 0.987 and 0.992, respectively, indicating good predictive ability. The calibration curve and decision curve further confirmed the accuracy and clinical practicability of the model. Conclusion The predictive model proposed in this study can accurately assess the risk of developing RILI in patients with NSCLC who have undergone radiotherapy, demonstrating its potential value in clinical practice.

ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the health check-up population， and to perform stratified management of patients with the low， medium， and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019， and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI， the MAFLD group was further divided into lean MAFLD group （125 individuals with BMI<24 kg/m²） and non-lean MAFLD group （943 individuals with BMI≥24 kg/m²）. Indicators including demographic data， past history， laboratory examination， and liver ultrasound were compared between groups. Fibrosis-4 （FIB-4） score， NAFLD fibrosis score （NFS）， aspartate aminotransferase-to-platelet ratio index （APRI）， and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-9.758， P<0.05）， proportion of male patients （χ²=137.555， P<0.05）， and levels of body weight （Z=-27.987， P<0.05）， BMI （Z=-32.714， P<0.05）， waist circumference （Z=-31.805， P<0.05）， hip circumference （Z=-26.342， P<0.05）， waist-hip ratio （Z=-28.554， P<0.05）， alanine aminotransferase （ALT） （Z=-25.820， P<0.05）， aspartate aminotransferase （AST） （Z=-16.894， P<0.05）， gamma-glutamyl transpeptidase （GGT） （Z=-25.069， P<0.05）， alkaline phosphatase （Z=-12.533， P<0.05）， triglyceride （Z=-27.559）， total cholesterol （Z=-7.833， P<0.05）， low-density lipoprotein cholesterol （LDL-C） （Z=-8.222， P<0.05）， and uric acid （UA） （Z=-20.024， P<0.05）， as well as a significantly higher proportion of patients with metabolic syndrome （MetS） （χ²=578.220， P<0.05）， significantly higher prevalence rates of hypertension （χ²=241.694， P<0.05）， type 2 diabetes （χ²=796.484， P<0.05）， and dyslipidemia （χ²=369.843， P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （HDL-C） （Z=23.153， P<0.001）. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=1.45， 95% confidence interval ［CI］： 1.203‍ ‍—‍ ‍1.737）， ALT （OR=1.05， 95%CI： 1.046‍ ‍—‍ ‍1.062）， LDL-C （OR=1.23， 95%CI： 1.102‍ ‍—‍ ‍1.373）， and comorbidity with MetS （OR=5.97， 95%CI： 4.876‍ ‍—‍ ‍7.316） were independently associated with MAFLD. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.736， P<0.05） and HDL-C （Z=2.679， P<0.05） and significant reductions in the proportion of male patients （χ²=28.970， P<0.05）， body weight （Z=-14.230， P<0.05）， BMI （Z=-18.188， P<0.05）， waist circumference （Z=-13.451， P<0.05）， hip circumference （Z=-13.317， P<0.05）， ALT （Z=-4.519， P<0.05）， AST （Z=-2.258， P<0.05）， GGT （Z=-4.592， P<0.05）， UA （Z=-4.415， P<0.05）， the proportion of patients with moderate or severe fatty liver disease or MetS （χ²=42.564， P<0.05）， and the prevalence rates of hypertension （χ²=12.057， P<0.05） and type 2 diabetes （χ²=3.174， P<0.05）. Among the patients with MAFLD， 10 patients （0.9%） had an FIB-4 score of >2.67， 4 patients （0.4%） had an NFS score of >0.676， 8 patients （0.7%） had an APRI of >1， and 551 patients （51.6%） had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing， but with a relatively low number of patients with a high risk of advanced fibrosis， and such patients need to be referred to specialized hospitals for liver diseases.

Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

ObjectiveHepatocyte nuclear factor 4-alpha (HNF4A) is a critical transcription factor in the liver and pancreas. Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1 (MODY1). Notably, MODY1 patients with HNF4A pathogenic mutations exhibit decreased responses to arginine and reduced plasma triglyceride levels, but the mechanisms remain unclear. This study aims to investigate the potential target genes transcriptionally regulated by HNF4A and explore its role in these metabolic pathways. MethodsA stable 293T cell line expressing the HNF1A reporter was overexpressed with HNF4A. RNA sequencing (RNA-seq) was performed to analyze transcriptional differences. Transcription factor binding site prediction was then conducted to identify HNF4A binding motifs in the promoter regions of relevant target genes. ResultsRNA-seq results revealed a significant upregulation of transmembrane 4 L six family member 5 (TM4SF5) mRNA in HNF4A-overexpressing cells. Transcription factor binding predictions suggested the presence of five potential HNF4A binding motifs in the TM4SF5 promoter. Finally, we confirmed that the DR1 site in the -57 to -48 region of the TM4SF5 promoter is the key binding motif for HNF4A. ConclusionThis study identified TM4SF5 as a target gene of HNF4A and determined the key binding motif involved in its regulation. Given the role of TM4SF5 as an arginine sensor in mTOR signaling activation and triglyceride secretion, which closely aligns with phenotypes observed in MODY1 patients, our findings provide novel insights into the possible mechanisms by which HNF4A regulates triglyceride secretion in the liver and arginine-stimulated insulin secretion in the pancreas.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.