BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

Objective To analyze the risk factors affecting the progression-free survival(PFS)of patients with intrahepatic cholangiocarcinoma(ICC)after surgical resection,and a predictive nomogram model was constructed based on blood test indicators.Methods A total of 99 ICC patients who received their first treatment at Hunan Provincial People's Hospital from January 2020 to December 2022 were selected as research subjects,they were divided into training group(n=70)and validation group(n=29).The independent risk factors for postoperative recurrence were identified using least absolute shrinkage and selection operator(LASSO)regression analysis and multivariate Cox risk regression analysis.The accuracy and clinical utility of the method were further tested by consistency index,receiver operating characteristic(ROC)curve,calibration graph,decision curve analysis,and progression-free survival curve.Results LASSO and multivariate Cox risk regression analysis showed that patient's gender,tumor-lymph node metastasis,differentiation grade,tumor diameter,aspartate aminotransferase,alpha-fetoprotein,total bile acid after surgery,and monocyte changes before and after surgery were independent factors affecting the PFS of ICC patients.The predictive model based on the risk factor showed that the consistency index of the training group was 0.884 and that of the validation group was 0.838.The area under ROC curve for training group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.965 and 0.923,respectively;for validation group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.821 and 0.923,respectively.The risk score calculated according to the nomogram divided ICC patients into high-risk group and low-risk group with high postoperative recurrence risk,and the median PFS in high-risk group was significantly shorter than that in low-risk group(P＜0.05).Conclusion The nomogram constructed by this study has good predictive effect and can be used as a supplementary evaluation for predicting PFS after ICC patients.

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

The machine learning is used increasingly and widely in acupuncture prescription optimization, intelligent treatment and precision medicine, and has obtained a certain achievement. But, there are still some problems remained to be solved such as the poor interpretability of the model, the inconsistency of data quality of acupuncture research, and the clinical application of constructed models. Researches in future should focus on the acquisition of high-quality clinical and experimental data sets, take various machine learning algorithms as the basis, and construct professional models to solve various problems, so as to drive the high-quality development of acupuncture research.
Acupuncture Therapy/trends* ; Machine Learning ; Humans ; Algorithms

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

Objective To analyze the risk factors affecting the progression-free survival(PFS)of patients with intrahepatic cholangiocarcinoma(ICC)after surgical resection,and a predictive nomogram model was constructed based on blood test indicators.Methods A total of 99 ICC patients who received their first treatment at Hunan Provincial People's Hospital from January 2020 to December 2022 were selected as research subjects,they were divided into training group(n=70)and validation group(n=29).The independent risk factors for postoperative recurrence were identified using least absolute shrinkage and selection operator(LASSO)regression analysis and multivariate Cox risk regression analysis.The accuracy and clinical utility of the method were further tested by consistency index,receiver operating characteristic(ROC)curve,calibration graph,decision curve analysis,and progression-free survival curve.Results LASSO and multivariate Cox risk regression analysis showed that patient's gender,tumor-lymph node metastasis,differentiation grade,tumor diameter,aspartate aminotransferase,alpha-fetoprotein,total bile acid after surgery,and monocyte changes before and after surgery were independent factors affecting the PFS of ICC patients.The predictive model based on the risk factor showed that the consistency index of the training group was 0.884 and that of the validation group was 0.838.The area under ROC curve for training group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.965 and 0.923,respectively;for validation group:PFS prediction at 6 months,1 year,and 2 years were 0.972,0.821 and 0.923,respectively.The risk score calculated according to the nomogram divided ICC patients into high-risk group and low-risk group with high postoperative recurrence risk,and the median PFS in high-risk group was significantly shorter than that in low-risk group(P＜0.05).Conclusion The nomogram constructed by this study has good predictive effect and can be used as a supplementary evaluation for predicting PFS after ICC patients.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n＝215) and MT (n＝103) significantly increased, and both DNT and DPT were significantly shortened (P＜0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P＝0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.

ObjectiveTo explore the effects and possible mechanism of Wenshen Tongdu Formula （温肾通督方， WTF） on spinal cord injury. MethodsThirty-six C57BL/6 female mice were randomly divided into sham operation group， model group and WTF group， with 12 mice in each group. The spinal cord injury model was established in the model group and the WTF group using the modified Allen's method， while in the sham operation group the spinal cord was only exposed. Since the 1st day after surgery， 50 g/（kg·d） of WTF solution was given to the WTF group by gavage， while 20 ml/（kg·d） of normal saline was given to the sham operation and model group by gavage， all for 14 days. Before surgery and on the 1st， 7th， and 14th days after surgery， the motor function of the mice was evaluated using the inclined plane test and hind limb motor function score （by BMS）. On the 3rd day after surgery， the nerve electrophy-siology was detected through electromyography and motor evoked potential； the spleen length was measured， and B cells in the spleen were sorted by magnetic beads； the differential expression of proteins were detected through proteomics technology； and the protein expression of mitochondrial outer membrane transport porin 20 （Tom20） and downstream cleaved caspase-3 in spleen B cells were measured using Western blotting. On the 14th day after surgery， MRI was used to observe the recovery of the spinal cord. ResultsCompared to those in the sham operation group at the same time， the BMS scores and subscores and the inclined plane test angle in the model group were reduced on the 1st， 7th and 14th days after surgery； the peak value of electromyogram and motor evoked potential were reduced， and the spleen length was shortened， while the expression of Tom20 and cleaved caspase-3 increased in splenic B cells increased （P＜0.05）. Compared to those in the model group at the same time， the BMS subscores on the 14th day and the angle of the inclined plane test on the 7th and 14th days after surgery increased in the WTF group； the peak value of electromyography and motor evoked potential， as well as the length of spleen increased， and the expression of Tom20 and cleaved caspase-3 decreased （P＜0.05）. The proteomics results showed that there were 100 differential proteins in the WTF group versus the model group， of which 37 were up-regulated and 63 were down-regulated. GO enrichment analysis showed that differential proteins mainly played their roles in oxygen binding， exogenous apoptosis negative feedback， zinc ion response， and oxygen transport. KEGG enrichment analysis showed that differential proteins were mainly concentrated in metabolic pathways， Huntington's disease， oxidative phosphorylation and other pathways. Subcellular localization showed that differential proteins were associated with mitochondria. Magnetic resonance imaging on the 14th day after surgery showed that the spinal cord structure of the mice in the sham operation group was intact， and the segments were clear， with normal spinal cord signal； the low signal area in the spinal cord injury area increased in the model group， and the spinal cord became significantly thinner； the injured segment had obvious depression in the WTF group， but the structure was more complete than that in the model group. ConclusionWTF may promote spinal cord injury repair by regulating immune function， and its mechanism may be related to inhibiting pyroptosis of spleen B cells.