Objective The purpose of this study is to observe the dynamic changes of host intestinal microflora during the evolution and development of the pathogenesis of"spleen qi deficiency syndrome-spleen yin deficiency syndrome",so as to explore its possible mechanism.Methods The rat model of spleen Qi deficiency syndrome was established by exhaustive swimming and improper diet rhythm.On this basis,the rat model of spleen-yin deficiency syndrome was established by combining the method of consuming yin fluid.Immune-associated cytokines were assessed using ELISA assay and altered composition and diversity in gut microbiota were observed via 16S rRNA sequencing analysis.Results Compared with the control group,sIgA,IL-4,IL-10 and TGF-β in the small intestine of the model group decreased,while IFN-γ and IL-17 levels increased(P<0.05,P<0.01).The changes of immune-related cytokines proved that the immune function of spleen deficiency rats was low.In addition,the intestinal flora structure of rats with spleen deficiency has also changed significantly.The proportion of Firmicutes and Bacteroides changed and the abundance of Proteobacteria increased.The abundance of some probiotics like Lactobacillus and Oscillospira decreased(P<0.01,P<0.05)while some pathogens like Clostridium,SMB53,Campylobacterales,Desulfovibrionales and Enterobacteriales increased(P<0.05).The characteristic changes of intestinal flora in spleen Qi deficiency stage were the abnormal increase of Allobaculum,Bifidobacterium,Prevotella and Adlercreutzia(P<0.01),while in spleen Yin deficiency stage was characterized by a significant increase in the abundance of Ruminococcus(P<0.05).Conclusion Spleen deficiency syndrome is closely related to the changes of intestinal microflora.The abundance of probiotics in the gut microbiota of rats with spleen deficiency syndrome decreased and the abundance of pathogenic bacteria increased.The gut microbiota changes dynamically in the development of spleen deficiency syndrome,which have their own characteristics in the spleen Qi deficiency and spleen Yin deficiency stage respectively.

Objective To compare the intestinal injury induced by different intensities of waveshock in rats exposed to extremely cold environment and to preliminarily explore the characteristics of the injury.Methods Sixty healthy male SD rats(2 months old,weighing 200～250 g)were randomly divided into 6 groups(n=10):blank control group,low-temperature control group,5.0 MPa shock control group,and low-temperature+4.0,4.5 and 5.0 MPa shock groups.The rats in the experimental groups were pre-treated in a-10℃low-temperature environment for 30 min and then subjected to intestinal injury by using BST-I biological shock tube with different driving pressures.At 3,8,and 24 h after injury,the serum levels of IL-6,TNF-α,intestinal fatty acid binding protein(I-FABP),and diamine oxidase(DAO)were detected,and the survival of rats within 24 h was recorded.At 24 h after injury,the rats were anesthetized and dissected,the characteristics of intestinal injury were observed,and pathological examination was performed.The differences of intestinal injury were compared among the 6 groups to explore the characteristics of intestinal injuries after different intensities of shockwave in rats after exposure to extremely cold environment.Results Compared with the blank control group,the other 5 groups exhibited different severities of intestinal injury,and the rats in the low-temperature+different shock groups were more prone to intestinal edema and trauma.The mortality rate was significantly increased in the low-temperature+5.0 MPa shock group(P<0.05).Pathological and serological studies found that dual effects of very cold environment and blast injury resulted in intestinal mucosal hemorrhage,edema,and disintegration of lamina propria in the experimental rats.The indicators of intestinal mucosal injury and intestinal inflammatory factors were also significantly increased when compared with the blank control group,and significant differences were among the groups with increment of shock intensity(P<0.05).Conclusion Exposure to very cold environment combined with abdominal blast injury increases mortality rate in rats,manifested by elevated serological indicators and intestinal inflammatory factors,as well as varying severities of intestinal wall edema and submucosal bleeding.Furthermore,the severity of the injury is positively related to the impact intensity,with worsened as the impact intensity increasing.

Objective This study aims to explore the effects of Minimally Invasive Extracorporeal Circulation(MECC)on systemic inflammatory response and transfusion requirements following Coronary Artery Bypass Grafting(CABG).Methods A total of 126 patients who underwent CABG from January 2023 to January 2024 were selected and randomly divided into an observation group and a control group,with 63 patients in each group.The observation group received MECC,while the control group was treated with Conventional Extracorporeal Circulation(CECC).Inflammatory response indicators,immune system function,coagulation function,renal function,cardiac function,and clinical symptoms were monitored preoperatively and at 24,48,and 72 hours postoperatively for comparison and analysis.Results At 24 hours postoperatively,CRP,IL-6 and TNF-α levels in the observation group were(18.5±3.7)mg/L,(15.2±3.4)pg/mL and(25.3±5.6)pg/mL,respectively,which were significantly lower than those in the control group(P＜0.05).At 48 hours postoperatively,the CD4+/CD8+ratio in the observation group was 1.6±0.3,which was higher than that in the control group(P＜0.05).At 72 hours postoperatively,the PT and APTT in the observation group were(12.1±1.2)seconds and(30.4±3.2)seconds,respectively,which were significantly lower than those in the control group(P＜0.05).Additionally,72 hours after surgery,SCr and BUN in the observation group were(1.1±0.2)mg/dL and 14.6±3.1 mg/dL,respectively,which were significantly lower than those in the control group(P＜0.05).In terms of cardiac function indexes,at 24 hours postoperatively,CI,LVEF,cTnⅠ and BNP in the observation group were(2.6±0.5)L/min/m2,(55.6±4.0)％,(0.14±0.03)ng/mL,and(280±30)pg/mL,respectively,which were significantly better than those in the control group(P＜0.05).At all postoperative time points,the VAS score,complication rate,length of hospital stay and ICU stay were significantly better in the observation group than in the control group(P＜0.05),with the VAS score at 24 hours postoperatively being(4.8±1.2)compared to(5.5±1.3)in the control group(P＜0.05).Conclusions MECC demonstrates significant advantages in attenuating systemic inflammatory response after CABG,protecting multi-system function,reducing postoperative blood transfusion requirements,and improving postoperative recovery.Compared with traditional extracorporeal circulation,MECC effectively reduce postoperative inflammatory reactions and complications,enhancing the quality of life for patients post-surgery,and shows broad clinical application prospects.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.

Objective To address the challenges of constructing large language models for traditional Chinese medicine(TCM)classics,which are complex and expensive to fine-tune,this study explores a lightweight fine-tuning method for such models,aiming to develop a question-answering model centered on TCM classics,particularly various editions of Shang Han Lun through the ages.Methods Dataset construction involved designing prompts to guide GPT-4 in generating Q&A pairs based on Shang Han Lun and integrating them with the ShenNong_TCM_Dataset and cMedQA2 datasets.Five general-purpose large models were selected for Lora fine-tuning.The best model was chosen through evaluation,and the performance of multiple quantized versions was validated.Results After fine-tuning,the BLEU,ROUGE-1,ROUGE-2,and ROUGE-L metrics for the Qwen-7B-Chat model improved by 17.61,19.63,14.3,and 21.4,respectively,compared to the base model.Conclusion The selected model in this study is capable of effectively understanding and utilizing professional terms and concepts from TCM classics,such as Shang Han Lun,to provide accurate answers to user queries.Compared to similar models,it requires lower fine-tuning costs and computational power,contributing to the dissemination of TCM knowledge and the development of intelligent systems.

Objective The purpose of this study is to observe the dynamic changes of host intestinal microflora during the evolution and development of the pathogenesis of"spleen qi deficiency syndrome-spleen yin deficiency syndrome",so as to explore its possible mechanism.Methods The rat model of spleen Qi deficiency syndrome was established by exhaustive swimming and improper diet rhythm.On this basis,the rat model of spleen-yin deficiency syndrome was established by combining the method of consuming yin fluid.Immune-associated cytokines were assessed using ELISA assay and altered composition and diversity in gut microbiota were observed via 16S rRNA sequencing analysis.Results Compared with the control group,sIgA,IL-4,IL-10 and TGF-β in the small intestine of the model group decreased,while IFN-γ and IL-17 levels increased(P<0.05,P<0.01).The changes of immune-related cytokines proved that the immune function of spleen deficiency rats was low.In addition,the intestinal flora structure of rats with spleen deficiency has also changed significantly.The proportion of Firmicutes and Bacteroides changed and the abundance of Proteobacteria increased.The abundance of some probiotics like Lactobacillus and Oscillospira decreased(P<0.01,P<0.05)while some pathogens like Clostridium,SMB53,Campylobacterales,Desulfovibrionales and Enterobacteriales increased(P<0.05).The characteristic changes of intestinal flora in spleen Qi deficiency stage were the abnormal increase of Allobaculum,Bifidobacterium,Prevotella and Adlercreutzia(P<0.01),while in spleen Yin deficiency stage was characterized by a significant increase in the abundance of Ruminococcus(P<0.05).Conclusion Spleen deficiency syndrome is closely related to the changes of intestinal microflora.The abundance of probiotics in the gut microbiota of rats with spleen deficiency syndrome decreased and the abundance of pathogenic bacteria increased.The gut microbiota changes dynamically in the development of spleen deficiency syndrome,which have their own characteristics in the spleen Qi deficiency and spleen Yin deficiency stage respectively.

Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.

Objective:To explore the association between environment exposure and hormone-sensitive cough in patients with chronic cough.Methods:Clinical data of 197 patients with chronic cough visited outpatient clinic of the Second Affiliated Hospital of Guangzhou Medical University from June 2016 to June 2021 were retrospectively analyzed, including 130 cases of corticosteroid responsive cough (CRC, 66.0%) and 67 cases of non-corticosteroid responsive cough (NCRC, 34.0%). The association between living environment exposure and hormone sensitivity was examined with a binary logistic regression analysis.Results:Among 197 patients with chronic cough, there were 82 males (41.6%) and 115 females (58.4%). 75.1% (148/197) had a history of smoking, and 16.8% (33/197) had a history of allergies. 66.0% (130/197) lived in the city center, 18.3% (36/197) had a chemical factory around their place of residence, 11.2% (22/197) renovated their homes within the first six months of the disease, 15.7% (31/197) purchase new furniture, 54.3% (107/197) plant flowers and plants in their houses, 21.3% (42/197) keep pets in their houses, 79.2% (156/197) had lived in their houses for more than 2 years, 71.1% (140/197) had cockroaches in their houses, 16.2% (32/197) had mold in their houses, 83.3% (164/197) had a frequency of air conditioning cleaning exceeds 2 months per time.There were 130 patients (66.0%) with CRC and 67 patients (34.0%) with NCRC.Binary logistic regression analysis showed that living close to the main road ( OR=2.296, 95% CI: 1.350-3.904, P=0.002), living near chemical factories ( OR=3.322, 95% CI: 2.158-5.573, P<0.001), history of allergy ( OR=2.175, 95% CI: 1.165-4.058, P=0.015), purchasing new furniture within 6 months ( OR=2.828, 95% CI: 1.402-5.706, P=0.004), cotton and linen curtains ( OR=1.875, 95% CI: 1.038-3.388, P=0.037) were positively correlated with CRC; while down and wool pillowcases and quilts ( OR=0.142, 95% CI: 0.033-0.602, P=0.008; OR=0.207, 95% CI: 0.067-0.640, P=0.006) and low ventilation frequency ( OR=0.281, 95% CI: 0.131-0.603, P=0.001) were negatively correlated with CRC. Conclusion:Hormone-sensitive cough patients account the most of chronic cough cases, and there are differences in the living environment exposure between CRC and NCRC patients, which provides information for corresponding interventions to prevent and manage CRC.

Phlegm and dampness are endogenous,rise and fall with Qi,reach the limbs,diffuse the whole body,and form obesity.Regulating phlegm dampness with traditional Chinese medicine can realize the early prevention and treatment of obesity.Intestinal microbiota participates in a variety of human metabolic processes.Regulating intestinal microbiota is a new way to prevent and treat obesity.Taking the close relationship between intestinal flora and its metabolites,obesity and phlegm dampness theory as the breakthrough point,and based on the existing research results,this paper discusses the possible role of intestinal microbiota and its metabolites in the formation of phlegm dampness and the prevention and treatment of obesity,It is considered that the common intestinal microbiota and its metabolites of different individuals with obesity caused by phlegm dampness may be used as specific indicators to become the new micro identification basis of obesity phlegm dampness theory.It is proposed that intestinal microbiota and its metabolites will become the key point of obesity phlegm dampness theory research,which will provide a new explanation for obesity prevention and control research,and expand new research fields for the connotation of TCM phlegm dampness theory.