ObjectiveQi deficiency and phlegm dampness syndrome is a common type of clinical traditional Chinese medicine（TCM） syndrome. However， there is no standard， scientific， and accurate report on the construction of animal models of Qi deficiency and phlegm dampness syndrome. This study aims to construct a mouse model of Qi deficiency and phlegm dampness syndrome by using a multi-factor composite modeling method and to evaluate the model. MethodsTwenty-one C57BL/6 mice were randomly divided into three groups with seven mice in each group， which were the normal group， model group， and Shenling Baizhusan （SLBZ） group. The control group was fed with ordinary diet and kept in a normal environment. The model group and SLBZ group were fed with a high-fat diet in a high-humidity environment. Swimming with heavy weights until exhaustion and gavage with cold water or lard were used to establish the mouse model of Qi deficiency and phlegm dampness syndrome. In order to test the syndrome by prescription， mice in the SLBZ group were treated with SLBZ for 14 days after model construction. The exhaustive swimming time， body weight， serum lipid levels， tongue changes， "Qi deficiency and phlegm dampness" assessment scale score， and cecal index of mice in each group were measured. The feces of each group of mice were sent for metagenomics and metabolome sequencing， and the changes in intestinal flora and metabolites were analyzed. ResultsAfter the modeling of Qi deficiency and phlegm dampness syndrome， the exhaustive swimming time of mice was obviously shortened （P<0.01）. The serum total cholesterol， low density lipoprotein cholesterol， and non-high density lipoprotein cholesterol of mice were significantly increased （all P<0.01）. The tongue of mice was significantly different from that of the normal group， and the score of the assessment scale was significantly higher than that of the control group （P<0.01）. Cecal index decreased significantly （P<0.01）. The serum lipid level， tongue image， assessment scale score， and cecal index were reversed in the SLBZ group. Metagenomic and metabolome sequencing results showed that intestinal flora and fecal metabolites were significantly changed in mice with Qi deficiency and phlegm dampness syndrome. Akkermansia_muciniphila， Faecalibaculum_rodentium， Eubacterium_plexicaudatum， Eubacterium sp 14_2， Candida glabrata， Romboutsia_ilealis， Turicibacter sp TS3， and other bacteria had significant changes， and the expressions of intestinal metabolites such as chenodeoxycholic acid， choline， L-phenylalanine betaine， and 2-phenylbutyric acid were significantly changed. Related metabolic pathways such as linoleic acid metabolism， primary bile acid biosynthesis， lysine degradation， arginine biosynthesis， and alpha-linolenic acid metabolism were affected. ConclusionThe Qi deficiency and phlegm dampness model of mice can be constructed by the multi-factor composite modeling method of high-fat diet feeding， high-humidity environment feeding， exhaustive swimming with heavy weight， and intragastric administration with cold water or lard. The blood lipid level， tongue change， score of "Qi deficiency and phlegm dampness assessment scale"， cecal index， and changes in related intestinal flora and metabolites of mice can be used as key indicators for model evaluation.

Objective:To investigate the efficacy of radiotherapy in postoperative metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treated with pyrotinib, and to identify potential subgroups that may benefit from this strategy.Methods:The clinical data of 187 patients with postoperative distant metastatic HER2-overexpressing breast cancer who received pyrotinib at the First Affiliated Hospital of Bengbu Medical University from January 2018 to July 2022 were retrospectively analyzed. The Kaplan-Meier method was used to assess changes in survival outcomes in patients undergoing radiotherapy. Univariate and multivariate analyses were conducted to identify prognostic factors, and the log-rank test was used to determine potential subgroups that may benefit from radiotherapy.Results:Among the 187 patients, 76 received radiotherapy. The median follow-up duration for the entire population was 16.9 months (range: 3.1-37.9 months), and the 2-year overall survival (OS) was 75.0%. Multivariate analysis showed that age, metastatic status, and radiotherapy were independent factors affecting OS (3.86-6.76, P<0.05). Further subgroup analysis showed that radiotherapy significantly improved OS in patients aged ≥50 years, those with oligometastases or bone metastases, those not receiving endocrine therapy, and those resistant to trastuzumab ( P<0.05). Conclusions:Radiotherapy, in addition to pyrotinib, can enhance the survival rate of patients with postoperative metastatic HER2-overexpressing breast cancer. The benefits of radiotherapy may be more pronounced in patients with a low tumor burden, inadequate systemic treatment, and drug resistance.

Objective:To investigate the efficacy of radiotherapy in postoperative metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treated with pyrotinib, and to identify potential subgroups that may benefit from this strategy.Methods:The clinical data of 187 patients with postoperative distant metastatic HER2-overexpressing breast cancer who received pyrotinib at the First Affiliated Hospital of Bengbu Medical University from January 2018 to July 2022 were retrospectively analyzed. The Kaplan-Meier method was used to assess changes in survival outcomes in patients undergoing radiotherapy. Univariate and multivariate analyses were conducted to identify prognostic factors, and the log-rank test was used to determine potential subgroups that may benefit from radiotherapy.Results:Among the 187 patients, 76 received radiotherapy. The median follow-up duration for the entire population was 16.9 months (range: 3.1-37.9 months), and the 2-year overall survival (OS) was 75.0%. Multivariate analysis showed that age, metastatic status, and radiotherapy were independent factors affecting OS (3.86-6.76, P<0.05). Further subgroup analysis showed that radiotherapy significantly improved OS in patients aged ≥50 years, those with oligometastases or bone metastases, those not receiving endocrine therapy, and those resistant to trastuzumab ( P<0.05). Conclusions:Radiotherapy, in addition to pyrotinib, can enhance the survival rate of patients with postoperative metastatic HER2-overexpressing breast cancer. The benefits of radiotherapy may be more pronounced in patients with a low tumor burden, inadequate systemic treatment, and drug resistance.

Objective To compare the root resorption of posterior teeth between fixed orthodontic appliances and clear aligners in adult patients with skeletal Class Ⅲ malocclusion undergoing camouflage treatment by using cone-beam computed tomography(CBCT)measurements.Methods Thirty-two cases of skeletal Class Ⅲ malocclusion patients who had previously undergone camouflage treat-ment were retrospectively selected.Based on the type of orthodontic appliance used,they were divided into two groups(the fixed appli-ance group and the clear aligner group),each comprising 16 cases.CBCT images of the entire dental arch before and after treatment were collected for these patients,and three-dimensional reconstructions of the mandibular central incisors,first premolars,and first molars were generated using Mimics software.Changes in root volume and length of mandibular teeth before and after treatment were measured and compared between the two groups.Results Both groups showed significant reductions in measured root volume of the teeth after orthodontic treatment(P＜0.05).In the clear aligner group,the mean reduction in root length of mandibular central incisors was(0.52±0.60)mm,while in the fixed appliance group,the reduction in root length of mandibular central incisors and first premolars was(0.47±0.38)mm and(0.38±0.25)mm,respectively.These differences were statistically significant(P＜0.05).Except for the sig-nificantly lower reduction in root volume of mandibular central incisors in the clear aligner group compared to the fixed appliance group(P＜0.05),there were no statistically significant differences in other root resorption-related parameters between the two groups(P＞0.05).Conclusion In camouflage treatment of adult skeletal Class Ⅲ malocclusion patients,clear aligners can reduce the amount of root resorption in mandibular anterior teeth to a certain extent compared to fixed orthodontic appliances.However,there is no significant difference between the two appliances in the posterior teeth region.

Objective To observe the clinical efficacy of Yinlian Gargle in the treatment of acute radiation-induced oropharyngeal mucositis after nasopharyngeal carcinoma radiotherapy.Methods Thirty-two patients with nasopharyngeal carcinoma,who had received first radiation,were randomly split into two groups:the trial group(19 cases)and the control group(13 cases).After all groups were treated with radiotherapy and chemotherapy,the control group was given rinse treatment with saline whereas the trial group was given Yinlian Gargle.The incidence of severe acute radiation-induced oropharyngeal mucositis,the duration and intensity of oropharyngeal discomfort and pain(NRS score),quality of life(QOL-NPC score),duration and intensity of radiation-induced side effects(SE-QOL-NPC score)and symptoms of dry mouth(SE1 score)were monitored before and after intervention in two groups.Results The incidence of grade Ⅲ or above radiation-induced oropharyngeal mucositis until the sixth week of radiotherapy in the trial group was considerably lower than that in the control group(P＜0.001),while the incidence of grade I or above radiation-induced oropharyngeal mucositis at 1 month after radiotherapy in the trial group was obviously lower than that in the control group(P＜0.001).The NRS score of pharyngeal discomfort of the trial group was lower than that of the control group starting from the second week of radiotherapy(P＜0.05).The NRS score of oral and oropharyngeal pain was lower than that of the control group starting from the fourth week of radiotherapy(P＜0.05).The SE1 score of the trial group was higher than that of the control group starting from the fifth week of radiotherapy(P＜0.05).After one month of the completion of the radiotherapy,the NRS score of pharyngeal discomfort and the NRS score of oral and oropharyngeal pain in the trial group were lower than those of the control group(P＜0.001).The QOL-NPC score,SE-QOL-NPC score,and SE1 score were all higher than those in the control group(P = 0.05 or P＜0.05).Conclusion Patients with nasopharyngeal cancer can greatly reduce their risk of developing severe acute radiation-induced oropharyngeal mucositis,effectively delay and relieve related symptoms,and enhance quality of life by consistently using Yinlian Gargle during radiotherapy.Additionally,a month after the completion of radiotherapy,it still has positive therapeutic effects on acute radiation-induced oropharyngeal mucositis.

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Objective:To investigate the efficacy of postmastectomy radiotherapy (PMRT) for human epidermal growth factor receptor 2 (HER2)-positive T 1-2N 1M 0 breast cancer in the context of HER2-targeted therapy. Methods:This study collected the clinical data of 105 female patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy in the First Affiliated Hospital of Bengbu Medical College from January 2013 to December 2019. Then, the clinical outcomes of these patients were observed, and the prognostic factors and the efficacy of PMRT were analyzed. Results:The median follow-up time was 50 months (ranging from 14 to 107 months), and the 5-year overall survival (OS), local-regional recurrence-free survival(LRFS), and disease-free survival (DFS) were 81.6%, 91.9%, and 76.2%, respectively. The multivariate analysis indicated that independent prognostic factors for OS and DFS include the age, pathologic grade, and tumor size; the independent risk factors for LRFS include positive lymph node ratio (LNR) and hormone receptor (HR) status; and the independent prognostic factor for DFS was PMRT (HR: 2.85, 95% CI: 1.10-8.80, P < 0.05). The subgroup analysis suggested that PMRT significantly improved the OS of various high-risk subgroups ( χ2=4.01-9.18, P < 0.05). However, the further stratified analysis indicated that PMRT only increased the OS of the patients who did not receive HER2-targeted therapy in various high-risk subgroups ( χ2=4.50-6.70, P < 0.05), while there was no statistical difference before and after PMRT for the individuals who received targeted treatment ( P > 0.05). Conclusions:PMRT is an independent prognostic factor for the DFS of patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy. PMRT can improve the OS of high-risk patients with ages < 45 years old, pathologic grade Ⅲ, tumor diameter ≥ 3 cm, LNR > 10%, and HR (-) who received no HER2-targeted therapy. However, the efficacy may be compromised to some extent in the context of the application of HER2-targeted therapy.

Objective:To explore the effects of the deep inspiration breath-hold (DIBH) technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy (IMN-IMRT) for postoperative left breast cancer.Methods:Totally 23 left breast cancer patients in the First Affiliated Hospital of Bengbu Medical College from Octorber 2021 to July 2022 receiving postoperative IMN-IMRT were enrolled in this study. The changes in dosimetric parameters for their heart and left anterior descending coronary artery (LAD) in the DIBH mode were observed, and the potential factors affecting DIBH effects were analyzed.Results:Compared with the free breath (FB) mode, the DIBH mode manifested a heart volume decrease by 18% ( t = 10.47, P < 0.001), a left lung volume increase by 42% ( t = -14.55, P < 0.001), and significantly reduced dosimetric parameters ( Dmean, Dmax, V5- V30) for the heart and LAD, exhibiting statistically significant differences ( t=-13.38 to -3.30, P<0.05). As indicated by the Pearson correlation analysis, the relative ratio of cardiac dose reduction was positively correlated with that of left lung expansion ( r = 0.82, P < 0.001) and negatively correlated with the patient′age ( r = -0.56, P = 0.005). Conclusions:DIBH can effectively reduce the heart and LAD radiation doses in IMN-IMRT for postoperative left breast cancer and that the patient's age, and the DIBH effects might be affected by the vital capacity.

Objective:To investigate the clinical characteristics and changing trends of primary liver cancer in Yunnan province from 2005 to 2014, in order to provide theoretical basis for the prevention and treatment of liver cancer in this region.Methods:A retrospective survey was used to select inpatient cases of liver cancer who were initially diagnosed and treated in our hospital from 2005 to 2014 with simple random sampling. Patients socio-demographic and clinicopathological characteristics were extracted by a unified and standardized questionnaire, and the data were statistically analyzed.Results:A total of 1000 cases with liver cancer were included, aged (53.2±11.2) years, with a male-to-female ratio of 5.99/1.00. There was no significant change in the gender and age composition ratio of patients in the past 10 years. The proportion of patients with lower education level (primary or junior high school) were increased from 21.8% to 23.4%, and the proportion of patients with relatively higher education level were decreased from 58% to 38.2% ( P<0.001). Smokers and non-smokers patients were decreased and increased from 58.8% to 44.4%, and 41.2% to 55.6% ( P<0.001). The proportion of drinker patients were decreased from 46.4% to 35.2%. The proportion of patients with advanced liver cancer (stage C and D) were increased, while the proportion of patients with stage A and B showed a downward trend ( P<0.001). The proportion of HBsAg-positive patients showed an upward trend, that is, rising from 69% in 2005 to 82% in 2014 ( P=0.043). The proportion of HBeAg-positive patients showed a steady trend ( P=0.008). The use rate of ultrasound examination in patients with liver cancer were decreased from 91.0% to 58.0% ( P=0.001), while the use rate of computed tomography (CT), MRI, and PET/CT examinations were increased from 81.0% to 84.0% ( P=0.05), 0 to 22% ( P<0.001), and 0 to 3% ( P=0.026) between 2005 to 2014. The proportion of surgical patients were increased ( P=0.005), but the proportion of interventional patients did not change significantly ( P=0.590). Surgery and interventional therapy were the most common treatment methods, and the proportion of patients treated with surgery over the past 10 years showed an upward trend ( P=0.005), while the proportion of interventional therapy remained at a high level with no significant change ( P=0.590). Conclusion:In Yunnan province, the incidence of liver cancer increases with age, and the proportion of male with liver cancer is almost six times that of women. Moreover, the low positive rate of alpha-fetoprotein levels and advanced clinical stage in this region are presently the main challenges against the liver cancer prevention and treatment. The application scope of CT, magnetic resonance imaging, PET-CT and other examination methods has gradually expanded, but the treatment methods are still mainly surgery and interventional therapy.

Objective:To observe the occurrence of epithelial-mesenchymal transition (EMT) in cervical cancer cell line Siha irradiated by X-rays with clinical conventional fraction radiotherapy model and investigate the role of exosomes in this process.Methods:Siha cells were irradiated by 6 MV-X rays with 50 Gy in 25 fractions. EMT was evaluated by cell morphology, EMT biomarkers and cell migration and invasion ability. Exosomes released from cells were detected by transmission electron microscopy and nanoparticle tracking analysis (NTA), and its function in EMT was explored by using an exosome inhibitor GW4869 (10 μmol/L).Results:After irradiation, EMT phenomenon was induced in the survived Siha cells, including the incidence of mesenchymal phenotype, upregulation of epithelial marker E-cadherin ( t=9.66, P<0.05), downregulation of mesenchymal marker N-cadherin ( t=41.61, P<0.05), and increase of cell migration and invasion abilities ( t=6.11, 13.22; P<0.05). Meanwhile, the secretion of exosomes was also increased after irradiation ( t=7.51, P<0.05). When the cells were pre-treated with GW4869, radiation-induced exosome secretion was reduced ( t=7.28, P<0.05), so that radiation-induced EMT was reversed. Conclusions:Ionizing radiation with clinical conventional fraction radiotherapy model promotes EMT of cervical cancer cells through increasing the secretion of exosomes.