This article introduces the experience of Academician SHI Xuemin in treatment of stroke combined with obstructive sleep apnea hypopnea syndrome. It is believed that this disease is the syndrome of "stroke of lung qi exhaustion". It is rooted at the deficiency of primary qi, and lung qi declining; and characterized by phlegm stagnation, qi reversion and mind blockage. This disease is manifested as somnolence-like symptoms, snoring-like breathing and sawing-like expectorating. The therapeutic regimen focuses on "governing qihai (sea of qi ), regulating the spirit and adjusting the orifice closure". The main acupoints include Neiguan (PC6), Shuigou (GV26) and Sanyinjiao (SP6) to regain the consciousness and open the orifices. Besides, Renying (ST9) is added to regulate the respiration, Baihui (GV20) and Sishencong (EX-HN1) to harmonize the spirit, and Fengchi (GB20), Wangu (GB12) and Yifeng (TE17) to open the orifice for the treatment of symptoms. It provides a new idea for the clinical diagnosis and treatment of stroke with accompanying symptoms.
Humans ; Sleep Apnea, Obstructive/complications* ; Acupuncture Therapy ; Stroke/physiopathology* ; Male ; Acupuncture Points ; Female ; Middle Aged ; Qi ; Aged ; Lung/physiopathology* ; Snoring/physiopathology* ; Adult ; Drugs, Chinese Herbal/administration & dosage*

Based on the theory of the liver's"using bitter herbs to nourish or purge"from Huangdi Neijing,this paper systematically elucidates the theoretical foundation for treating functional constipation from liver.Focusing on the physiological characteristic of"liver desires to disperse"and the pathological manifestation of"liver bitterness and urgency,"combined with the"liver communicates with the large intestine"theory,this paper establishes a diagnostic and therapeutic framework for managing functional constipation by regulating liver function.The pathological evolution of functional constipation manifests in three distinct stages:in the early stage,liver qi stagnation leads to large intestine qi obstruction,where damaged by an excess of seven emotions resulting in symptoms such as difficult defecation,abdominal bloating,and hypochondriac pain;in the middle stage,liver depression transforms into fire,scorching bodily fluids to generate dryness,thereby creating a pathological interplay of stagnation,fire,and dryness,which is marked by anal heat,dry mouth,and yellow urine;in the late stage,yin deficiency in liver and kidney causes large intestine malnutrition,resulting in a complex pathological state where yin deficiency,collateral blockage,dryness accumulation,and blood stasis intertwine,clinically manifesting as pellet-like stools(resembling sheep feces)and soreness and weakness of the waist and knees.In treatment,the formula design follows the principle of"sweetness to relieve,acridity to tonify,and sourness to purge,"with treatment principles varying across stages.In the early stage,the focus is on dispersing liver and regulating qi,and unblocking the zang-fu viscera;in the middle stage,the priority shifts to clearing heat-fire,nourishing large intestine,and promoting fluid production;whereas,in the late stage,the emphasis lies on nourishing yin,unblocking collaterals,and promoting blood circulation.This staged treatment of functional constipation overcomes the limitations of solely focusing on nourishing large intestine and facilitating feces excretion,thereby advancing the treatment of different stages based on syndrome differentiation and personalized treatment.It provides theoretical support for improving patients' intestinal function and enhancing overall health outcomes.

Objective:To explore the prognostic value of artificial intelligence-based P53 and Ki67 detection in stage I non-mucinous adenocarcinoma(INMA)of lung.Methods:A retrospective analysis was made of patients treated by radical surgical resection for INMA of lung in the Department of Thoracic Surgery of Peking University First Hospital from Jan.2015 to Dec.2016,with complete clinicopathological and 5-year follow-up data.Immunohistochemical staining for P53 and Ki67 was performed on all cases and the index of P53 and Ki67 was calculated with the assistance of artificial intelligence(AI).The optimal cut-off values for P53 and Ki67 were determined using X-Tile software,and based on these values,the patients were divided into low-expression and high-expression groups.Pearson chi-square test and Fisher's exact test were used to compare the differences in clinicopathological characteristics between the different groups.Univariate and multivariate Cox regression analyses were performed to assess the impact of various indicators on 5-year overall survival(OS)and disease-free survival (DFS)for stage I INMA.The time-dependent receiver operating characteristic(ROC) curves and the area under the curve(AUC)was used to analyze the predictive performance of P53 and Ki67 for the prognosis of stage I INMA.Results:Among the 191 patients, the median follow-up time was 60(54, 60) months. The index of P53 and Ki67 were 0%-100% and 1.0%-78.0%,respectively. The X-Tile software revealed optimal cut-off values of 62% for P53 and 20% for Ki67.Then the patients were divided into P53 low-expression group (<62%), P53 high-expression (≥62%) group and Ki67 low-expression (<20%)group,Ki67 high-expression group (≥20%). High expression of P53 was associated with male ( χ2=12.45, P<0.001), smoking ( χ2=12.24, P<0.001), pTNM stage ( χ2=16.28, P<0.001), and histological grade ( P<0.001). High expression of Ki67 was associated with male ( χ2=17.33, P<0.01), smoking ( χ2=21.67, P<0.01), and histological grade ( P<0.001). Male ( HR=2.612, 95% CI: 1.173-5.815, P=0.019), smoking ( HR=2.651, 95% CI: 1.246-5.642, P=0.011), high pTNM stage ( HR=3.815, 95% CI: 1.792-8.122, P<0.001), high histological grade ( HR=5.277, 95% CI: 2.400-11.606, P<0.001), high P53 expression ( HR=5.950, 95% CI: 2.792-12.680, P<0.001), and high Ki67 expression ( HR=3.349, 95% CI: 1.554-7.221, P=0.002) were associated with poorer disease-free survival (DFS). Male ( HR=9.050, 95% CI: 1.113-73.586, P=0.039), smoking ( HR=8.428, 95% CI: 1.701-41.765, P=0.009), high histological grade ( HR=6.865, 95% CI: 1.756-26.834, P=0.006), high P53 expression ( HR=16.699, 95% CI: 3.369-82.761, P<0.001), and high Ki67 expression ( HR=7.558, 95% CI: 1.806-31.632, P=0.006) were associated with poorer overall survival. P53 high-expression was identified as an independent risk factor for both DFS ( HR=2.843, 95% CI: 1.192-6.778, P=0.018) and OS( HR=6.909, 95% CI: 1.202-39.720, P=0.030) in stage I INMA patients. The area under the time-dependent ROC curves for predicting 5-year overall survival after surgery were 0.738 for p53, 0.674 for Ki67, 0.638 for pTNM staging, and 0.587 for histological grade. Among these, p53 demonstrated the highest predictive efficacy. Conclusions:AI-assisted interpretation of P53 and Ki67 indices improves test result repeatability. With critical values of 62% and 20%, high P53 and Ki67 expression indicates poor prognosis, while high P53 expression is an independent risk factor for lower OS and DFS, serving as a reference for postoperative adjuvant therapy screening.

Based on the theory of the liver's"using bitter herbs to nourish or purge"from Huangdi Neijing,this paper systematically elucidates the theoretical foundation for treating functional constipation from liver.Focusing on the physiological characteristic of"liver desires to disperse"and the pathological manifestation of"liver bitterness and urgency,"combined with the"liver communicates with the large intestine"theory,this paper establishes a diagnostic and therapeutic framework for managing functional constipation by regulating liver function.The pathological evolution of functional constipation manifests in three distinct stages:in the early stage,liver qi stagnation leads to large intestine qi obstruction,where damaged by an excess of seven emotions resulting in symptoms such as difficult defecation,abdominal bloating,and hypochondriac pain;in the middle stage,liver depression transforms into fire,scorching bodily fluids to generate dryness,thereby creating a pathological interplay of stagnation,fire,and dryness,which is marked by anal heat,dry mouth,and yellow urine;in the late stage,yin deficiency in liver and kidney causes large intestine malnutrition,resulting in a complex pathological state where yin deficiency,collateral blockage,dryness accumulation,and blood stasis intertwine,clinically manifesting as pellet-like stools(resembling sheep feces)and soreness and weakness of the waist and knees.In treatment,the formula design follows the principle of"sweetness to relieve,acridity to tonify,and sourness to purge,"with treatment principles varying across stages.In the early stage,the focus is on dispersing liver and regulating qi,and unblocking the zang-fu viscera;in the middle stage,the priority shifts to clearing heat-fire,nourishing large intestine,and promoting fluid production;whereas,in the late stage,the emphasis lies on nourishing yin,unblocking collaterals,and promoting blood circulation.This staged treatment of functional constipation overcomes the limitations of solely focusing on nourishing large intestine and facilitating feces excretion,thereby advancing the treatment of different stages based on syndrome differentiation and personalized treatment.It provides theoretical support for improving patients' intestinal function and enhancing overall health outcomes.

Objective:To explore the prognostic value of artificial intelligence-based P53 and Ki67 detection in stage I non-mucinous adenocarcinoma(INMA)of lung.Methods:A retrospective analysis was made of patients treated by radical surgical resection for INMA of lung in the Department of Thoracic Surgery of Peking University First Hospital from Jan.2015 to Dec.2016,with complete clinicopathological and 5-year follow-up data.Immunohistochemical staining for P53 and Ki67 was performed on all cases and the index of P53 and Ki67 was calculated with the assistance of artificial intelligence(AI).The optimal cut-off values for P53 and Ki67 were determined using X-Tile software,and based on these values,the patients were divided into low-expression and high-expression groups.Pearson chi-square test and Fisher's exact test were used to compare the differences in clinicopathological characteristics between the different groups.Univariate and multivariate Cox regression analyses were performed to assess the impact of various indicators on 5-year overall survival(OS)and disease-free survival (DFS)for stage I INMA.The time-dependent receiver operating characteristic(ROC) curves and the area under the curve(AUC)was used to analyze the predictive performance of P53 and Ki67 for the prognosis of stage I INMA.Results:Among the 191 patients, the median follow-up time was 60(54, 60) months. The index of P53 and Ki67 were 0%-100% and 1.0%-78.0%,respectively. The X-Tile software revealed optimal cut-off values of 62% for P53 and 20% for Ki67.Then the patients were divided into P53 low-expression group (<62%), P53 high-expression (≥62%) group and Ki67 low-expression (<20%)group,Ki67 high-expression group (≥20%). High expression of P53 was associated with male ( χ2=12.45, P<0.001), smoking ( χ2=12.24, P<0.001), pTNM stage ( χ2=16.28, P<0.001), and histological grade ( P<0.001). High expression of Ki67 was associated with male ( χ2=17.33, P<0.01), smoking ( χ2=21.67, P<0.01), and histological grade ( P<0.001). Male ( HR=2.612, 95% CI: 1.173-5.815, P=0.019), smoking ( HR=2.651, 95% CI: 1.246-5.642, P=0.011), high pTNM stage ( HR=3.815, 95% CI: 1.792-8.122, P<0.001), high histological grade ( HR=5.277, 95% CI: 2.400-11.606, P<0.001), high P53 expression ( HR=5.950, 95% CI: 2.792-12.680, P<0.001), and high Ki67 expression ( HR=3.349, 95% CI: 1.554-7.221, P=0.002) were associated with poorer disease-free survival (DFS). Male ( HR=9.050, 95% CI: 1.113-73.586, P=0.039), smoking ( HR=8.428, 95% CI: 1.701-41.765, P=0.009), high histological grade ( HR=6.865, 95% CI: 1.756-26.834, P=0.006), high P53 expression ( HR=16.699, 95% CI: 3.369-82.761, P<0.001), and high Ki67 expression ( HR=7.558, 95% CI: 1.806-31.632, P=0.006) were associated with poorer overall survival. P53 high-expression was identified as an independent risk factor for both DFS ( HR=2.843, 95% CI: 1.192-6.778, P=0.018) and OS( HR=6.909, 95% CI: 1.202-39.720, P=0.030) in stage I INMA patients. The area under the time-dependent ROC curves for predicting 5-year overall survival after surgery were 0.738 for p53, 0.674 for Ki67, 0.638 for pTNM staging, and 0.587 for histological grade. Among these, p53 demonstrated the highest predictive efficacy. Conclusions:AI-assisted interpretation of P53 and Ki67 indices improves test result repeatability. With critical values of 62% and 20%, high P53 and Ki67 expression indicates poor prognosis, while high P53 expression is an independent risk factor for lower OS and DFS, serving as a reference for postoperative adjuvant therapy screening.

Objective:To investigate the clinicopathological characteristics and possible pathogenesis of immune checkpoint inhibitor (ICI) induced myocarditis, and to improve understanding of this new type of myocarditis.Methods:Two cases of ICI induced myocarditis with endomyocardial biopsy available for review were selected from the cases with immune-related adverse events treated by ICI in Peking University First Hospital, Beijing, China from 2020 to 2022. The clinical data, histomorphological characteristics, PD-L1 expression of cardiomyocytes, and classification of inflammatory cells in two cases of ICI-induced myocarditis were analyzed. Relevant literature was reviewed.Results:Case 1 was a 64-year-old male diagnosed with gastric signet ring cell carcinoma. Case 2 was a 56-year-old male ad diagnosed with lung squamous cell carcinoma. Both patients developed acute myocarditis during PD-1 inhibitor treatment, and the disease progressed rapidly. Case 2 was more serious than case 1. Endomyocardial biopsy showed definite cardiomyocytic injury and prominent inflammatory infiltration in both cases, which met the full Dallas criteria for myocarditis. The degenerated and necrotic cardiomyocytes accounted for about 10% of the tissues in case 1 and 30% in case 2, respectively. In case 1, the inflammatory cells counted in the densest area were about 150/HPF, comprised of CD20 + cells (about 5/HPF), CD3 + cells (about 60/HPF), CD8 + cells (about 50/HPF) and CD68 + cells (about 70/HPF). In case 2, the inflammatory cells counted in the densest area were about 350/HPF, comprised of CD20 + cells (0/HPF), CD3 + cells (about 100/HPF), CD8 + cells (about 90/HPF) and CD68 + cells (about 200/HPF). In both cases, PD-L1 + cardiomyocytes aggregated in the inflammatory lesions, and the percentage was about 8% and 30% in case 1 and case 2, respectively. Conclusions:ICI-induced myocarditis is frequently acute onset, severe symptoms, and rapid progression. The histological morphology meets the full Dallas criteria for myocarditis. Expression of PD-L1 in cardiomyocytes can be detected in the inflammatory lesions. The inflammatory cells are comprised of CD8 + T lymphocytes and macrophages and the number of macrophages significantly exceeds that of lymphocytes. Combined with the pathological characteristics and the history of ICI treatment, the diagnosis of ICI-induced myocarditis can be made.

Carcinogenesis ; Cell Transformation, Neoplastic ; Hepatoblastoma ; Humans ; Liver ; Liver Neoplasms ; Organoids ; YAP-Signaling Proteins

Objective To investigate the effects of cyclic stretch on migration of MC3T3-E1 cells and its related mechanism. Methods The strain loading system was used to stretch MC3T3-E1 cells cultured in vitro with 15% amplitude, to simulate the mechanical condition in vivo. The wound healing assay was used to detect the migration of MC3T3-E1 cells. Western blotting was used to test Runx2 expression. RNA interfering was used to decrease Runx2 expression. Results Cyclic mechanical stretch with 15% amplitude, 1.25 Hz frequency and lasting for 24 hours could promote the migration of MC3T3-E1 cells and increase the expression level of Runx2. Runx2 interference inhibited the migration of MC3T3-E1 cells in static culture condition. Interference with Runx2 expression in MC3T3-E1 cells could partially reduce the positive effect of cyclic mechanical stretch on cell migration. Conclusions Cyclic stretch can promote the migration of MC3T3-E1 cells, and Runx2 may play an important role in this process. This study provides experimental basis for finding innovative clinical treatment method to promote fracture healing.

OBJECTIVE：To improve the level of pharmaceutical care，enhance the professional value and social status of pharmacists by clarifying the development process of pharmaceutical care and summarizing the value of pharmacists in pharmaceutical care. METHODS：The development process of pharmaceutical care at home and abroad（service objects，service contents and service methods）was summarized；the current situation of pharmaceutical care in China was analyzed；the value of pharmaceutical care were defined in respects of rational drug use，humanistic value and medical resources. The development of pharmaceutical care in the future was prospected. RESULTS & CONCLUSIONS：The development of pharmaceutical care can be divided into three stages：“drug supply as the center”“promoting rational drug use as the center”and“patients as the center”，and the service objects，service contents and service methods in different stages are expanding and diversifying. Compared with developed countries，the overall level of pharmaceutical care in China lags behind，and there are differences in level of pharmaceutical care modes in hospitals at different levels. Pharmacists ensure the safety，effectiveness and economy of drug use through pharmaceutical care，and promote rational drug use；the compliance，quality of life and satisfaction of patients have been improved through pharmaceutical care；pharmacists participate in medical quality management to save medical and health resources through pharmaceutical care. Pharmaceutical care，as an important part of the medical and health system，plays an important and irreplaceable role in the medical process，which is suggested that the relevant government departments should fully understand the value of pharmaceutical care and further strengthen their support for pharmaceutical care；pharmaceutical staff should improve their self-cultivation and cooperate with other disciplines to achieve the sustainable development of hospital pharmacy in different regions and medical institutions.

OBJECTIVE：To systematically evaluate the efficacy an d s afety of apatinib combined with transcatheter arterial chemoembolization（TACE）in the treatment of moderate and advanced liver cancer ，and to provide evidence-based reference for rational drug use in the clinic. METHODS ：Retrieved from Cochrane Library ，Embase，PubMed，Web of Science ，SinoMed， CNKI，Wanfang，VIP database ，RCTs about apatinib combined with TACE （trial group ）versus TACE （control group ）in the treatment of moderate and advanced liver cancer were collected from inception to Sep. 2019. After screening the literature and extracting the data ，the quality of included literatures was evaluated by using bias risk assessment tool recommended by the Cochrane system evaluator manual 5.1.0 and the modified Jadad scale. Meta-analysis was carried out by using Stata 12.0 software. RESULTS：Totally 16 RCTs were included ，involving 1 043 patients. Results of Meta-analysis showed that objective response rate [OR ＝3.10，95％CI（2.38，4.03），P＜0.001]，disease control rate [OR ＝3.56，95％CI（2.62，4.83），P＜0.001] and survival rate [OR ＝2.40，95％ CI（1.86，3.10），P＜0.001]，the incidence of diarrhea [OR ＝2.27，95％ CI（1.21，4.24），P＝0.011]， hypertension [OR ＝6.97，95％ CI（1.21，40.15），P＝0.030]， proteinuria [OR ＝12.44，95％CI（2.51，61.71），P＝0.002] and com hand foot syndrome [OR ＝32.50，95％CI（12.03，87.77），P＝ 0.001] of trial group were significantly higher than those of control group. The serum level of VEGF [SMD ＝－ 3.64， 95％CI（－5.06，－2.22），P＜0.001]，MMP-9 [SMD＝－3.21，95％CI（－4.31，－2.10），P＜0.001]，AFP [SMD ＝－3.54， 95％CI（－7.03，－0.06），P＝0.046] after treatment ，the incidence of myelosuppression [OR ＝0.61，95％CI（0.39，0.97），P＝ 0.035]，fever [OR ＝0.63，95％CI（0.42，0.95），P＝0.027]，nausea and vomiting [OR ＝0.70，95％CI（0.51，0.97），P＝0.030] in trial group were significantly lower than those of control group. There was no statistical significance in the incidence of abdominal pain [OR ＝0.87，95％CI（0.54，1.39），P＝0.547] and skin itching [OR ＝1.63，95％CI（0.36，7.50），P＝0.530] between 2 groups. CONCLUSIONS：Apatinib combined with TACE can significantly improve clinical efficacy ，prolong survival time ，reduce tumor recurrence and metastasis. It can reduce the occurrence of related ADR as diarrhea after TACE ，but increase the occurrence of apatinib-related ADR as myelosuppression.