Patients with chronic obstructive pulmonary disease have the disease phenomenon of fear of exercise because of dyspnea, which can accelerate the body degradation rate, weaken muscle strength, reverse increase dyspnea, and delay the recovery of the disease. As a result, this article examines the theoretical underpinnings and specific measures of dyspnea belief intervention programs for chronic obstructive pulmonary disease patients at home and abroad, summarizes the limitations of previous studies, and makes pertinent recommendations in an effort to serve as a guide for early patient prevention and the development of scientific and feasible intervention programs.

Objective:To discuss the effect of Wnt/β-catenin signaling pathway inhibitor methyl 3-｛[(4-methyl-phenyl)sulfonyl]amino ｝ benzoate(MS AB)on the fibrogenic response of the human endometrial stromal cells(HESCs),and to provide the foundation for the application of MSAB in the target therapy of intrauteriue adhesion(JUA).Methods:The normal HESCs were cultured in vitro and divided into two groups:control group and transforming growth factor β1(TGF-β1)group;the HESCs from the adhesion part of the IUA patients were cultured in vitro,regarded as IUA group.Western blotting method was used to detect the expression levels of fibrotic marker protein type Ⅰ collagen α1(COL1A1)in the cells in various groups at different time points(0,12,24,48,and 60 h)after treated with TGF-β1.MTT assay was used to detect the proliferation activities of the cells in various groups.Western blotting method was used to detect the expression levels of the fibrotic marker protein COL1A1,stromal marker proteins such as N-cadherin and α-smooth muscle actin(α-SMA),and Wnt/β-catenin signaling pathway-related protein β-catenin in the cells in control and IUA groups.Based on the MSAB concentrations,the normal HESCs were divided into 0(control),0.25,0.50,0.75,and 1.00 μmol·L-1 MSAB groups,and MTT assay was used to detect the survival rates of the cells in various groups.After treated with MSAB,the normal HESCs were divided into control group(normal HESCs),TGF-β1 group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with complete culture medium,and the cells continued to be cultured for 24 h),and MSAB group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with a complete medium containing 0.75 μmol·L-1 MSAB and the cells continued to be cultured for 24 h).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)-related transcription factors Snail,Slug,Smuc,ZEB1,and ZEB2,and COL1A1 mRNA in the cells in various groups.Western blotting method was used to detect the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in various groups.Results:Compared with control group(after treated with TGF-β1 for 0 h),the expression levels of COL1A1 proteins in the HESCs after treated with TGF-β1 for 12,24,48,and 60 h in TGF-β1 group were increased(P＜0.05 or P＜0.01).Compared with control group,there was no significant difference in the proliferation activity of the HESCs in IUA and TGF-β1 groups(P＞0.05).Compared with control group,the expression levels of COL1A1,β-catenin,N-cadherin,and α-SMA proteins in the cells in IUA group were increased(P＜0.05 or P＜0.01).Compared with control group,the survival rates of the cells in 0.75 and 1.00 μmol·L-1 MSAB groups were decreased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in TGF-β1 group were increased(P＜0.05 or P＜0.01);compared with TGF-β1 group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Compared with control group,after treated with TGF-β1 for 24 h,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in TGF-β1 group were increased(P＜0.01);compared with TGF-β1 group,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Conclusion:MSAB can inhibit the fibrogenic responses of the HESCs in vitro,and the results provide the theoretical basis for the application of MSAB in the target therapy of IUA.

Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.

Objective:To investigate damaging effects of clomifene citrate(CC)on endometrial stromal cells(hEndoSCs),and to study effects of spermidine on autophagy and inflammatory cytokine expression in damaged endometrial stromal cells.Methods:Groups were firstly divided into control group,spermidine group,clomiphene group(CC group),CC+Spermidine group.MTT assay was used to detect cell survival rate of hEndoSCs after co-incubation with different concentrations of CC or Spermidine for 24 h.Con-tent of intracellular reactive oxygen species(ROS)and level of apoptosis in cells of the 4 groups were detected by flow cytometry tech-nique.Western blot was used to detect expressions of autophagy pathway-related proteins ULK1,p-ULK1,LC-3Ⅱ,and apoptosis-re-lated proteins Bax,Bcl-2,Cleaved-caspase 3.RT-qPCR was used to detect mRNA expressions of IL-6,IL-1β and TNF-α.Results:Compared with control group,CC group showed decreased cell survival,increased apoptosis rate,ROS content,Bax,Cleaved-cas-pase 3 expressions,decreased Bcl-2 expression,decreased levels of autophagy-related proteins p-ULK1 and LC-3Ⅱ/Ⅰ,and elevated expressions of inflammatory factors IL-6,IL-1β and TNF-α mRNA(P<0.01).There was no significant changes viability of cells in spermidine group compared with control group(P>0.05).Compared with CC group,cell survival rate in CC+spermidine group was sig-nificantly increased,apoptosis rate,ROS content,Bax and Cleaved-caspase 3 expressions were decreased,Bcl-2 expression was in-creased,expressions of autophagy-related proteins p-ULK1 and LC-3Ⅱ/Ⅰ were elevated,while expressions of inflammatory factors IL-6,IL-1β and TNF-α mRNA were decreased(P<0.01).Conclusion:CC can inhibit endometrial stromal cell proliferation,promote apoptosis,and increase the transcript levels of inflammatory factors IL-6,IL-1β and TNF-α.Spermidine can reduce intracellular ROS in clomiphene-injured endometrial stromal cells by activating cellular autophagy,increase cell survival,and inhibit the expressions of inflammatory factors IL-6,IL-1β and TNF-α.

Objective:To develop and validate a predictive model of 28-day mortality in sepsis based on lactate dehydrogenase-to-albumin ratio (LAR).Methods:Sepsis patients diagnosed in the department of intensive care medicine of the First Affiliated Hospital of Soochow University from August 1, 2017 to September 1, 2022 were retrospective selected. Clinical data, laboratory indicators, disease severity scores [acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure assessment (SOFA)] were collected. Patients were divided into death group and survival group according to whether they died at 28 days, and the difference between the two groups was compared. The dataset was randomly divided into training set and validation set according to 7∶3. Lasso regression method was used to screen the risk factors affecting the 28-day death of sepsis patients, and incorporating multivariate Logistic regression analysis (stepwise regression) were included, a prediction model was constructed based on the independent risk factors obtained, and a nomogram was drawn. The nomogram prediction model was established. Receiver operator characteristic curve (ROC curve) was drawn to analyze and evaluate the predictive efficacy of the model. Hosmer-Lemeshow test, calibration curve and decision curve analysis (DCA) were used to evaluate the accuracy and clinical practicability of the model, respectively.Results:A total of 394 patients with sepsis were included, with 248 survivors and 146 non-survivors at 28 days. Compared with the survival group, the age, proportion of chronic obstructive pneumonia, respiratory rate, lactic acid, red blood cell distribution width, prothrombin time, activated partial thromboplastin time, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, blood potassium, blood phosphorus, LAR, SOFA score, and APACHEⅡ score in the death group were significantly increased, while oxygenation index, monocyte count, platelet count, fibrinogen, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and blood calcium were significantly reduced. In the training set, LAR, age, oxygenation index, blood urea nitrogen, lactic acid, total cholesterol, fibrinogen, blood potassium and blood phosphorus were screened by Lasso regression. Multivariate Logistic regression analysis finally included LAR [odds ratio ( OR) = 1.029, 95% confidence interval (95% CI) was 1.014-1.047, P < 0.001], age ( OR = 1.023, 95% CI was 1.005-1.043, P = 0.012), lactic acid ( OR = 1.089, 95% CI was 1.003-1.186, P = 0.043), oxygenation index ( OR = 0.996, 95% CI was 0.993-0.998, P = 0.002), total cholesterol ( OR = 0.662, 95% CI was 0.496-0.865, P = 0.003) and blood potassium ( OR = 1.852, 95% CI was 1.169-2.996, P = 0.010). A total of 6 predictor variables were used to establish a prediction model. ROC curve showed that the area under the curve (AUC) of the model in the training set and validation set were 0.773 (95% CI was 0.715-0.831) and 0.793 (95% CI was 0.703-0.884), which was better than APACHEⅡ score (AUC were 0.699 and 0.745) and SOFA score (AUC were 0.644 and 0.650), and the cut-off values were 0.421 and 0.309, the sensitivity were 62.4% and 82.2%, and the specificity were 82.2% and 68.9%, respectively. The results of Hosmer-Lemeshow test and calibration curve showed that the predicted results of the model were in good agreement with the actual clinical observation results, and the DCA showed that the model had good clinical application value. Conclusion:The prediction model based on LAR has a good predictive value for 28-day mortality in patients with sepsis and can guide clinical decision-making.

Objective To observe the effect on clinical efficacy and renal microcirculation(RMC)of Shenshuai Ⅱ Prescription Granules in the treatment of patients with stage 3-4 chronic kidney disease(CKD)caused by primary glomerulonephritis(PGN)with deficiency of spleen and kidney qi syndrome.Methods Using a randomized,double-blind clinical trial design,70 patients with CKD stage 3-4 were divided into the treatment group and the control group,with 35 cases in each group.The control group was given CKD integrated treatment combined with placebo granules,and the treatment group was given CKD integrated treatment combined with Shenshuai Ⅱ Prescription Granules.The clinical efficacy of both groups was observed.TCM symptom scores,renal function indexes and RMC indexes before and after treatment of the two groups were compared.Safety indexes of both groups were monitored.Results The total effective rate was 82.86％(29/35)in the treatment group and 54.29％(19/35)in the control group,with statistical significance(P<0.05).Compared with before treatment,all the TCM symptom scores of the 2 groups were reduced after treatment(P<0.05,P<0.01);after treatment,the 5 spleen and kidney qi deficiency symptom scores and the total score of the treatment group were lower than those of the control group(P<0.05).The mean values of renal cortical and medullary blood flow were elevated in the treatment group after treatment compared with the pre-treatment period in this group(P<0.05,P<0.01);the mean values of renal cortical and medullary blood flow were elevated in the treatment group compared with the control group in the post-treatment period(P<0.05,P<0.01).Compared with before treatment,the serum content of NO increased(P<0.01),ET-1 and VEGF decreased(P<0.01);after treatment,the serum content of NO in the treatment group was higher than that in the control group(P<0.05),and ET-1 and VEGF in the treatment group were lower than those in the control group(P<0.01).Compared with before treatment,SCr,BUN,24 hUP decreased and eGFR increased in the treatment group(P<0.05,P<0.01);after treatment,SCr,BUN,and 24 hUP in the treatment group were lower than those in the control group,and eGFR in the treatment group was higher than that in the control group(P<0.01).Compared with this group before treatment and between groups after treatment,the difference in Uric acid between the 2 groups was not statistically significant(P>0.05).There was no abnormal change in safety indexes before and after treatment in both groups(P>0.05).Conclusion Shenshuai Ⅱ Prescription Granules combined with CKD integrated treatment can effectively improve clinical symptoms and renal function related indexes of CKD stage 3-4 patients with spleen and kidney qi deficiency syndrome,increase renal blood flow,improve RMC disorder,and improve clinical efficacy.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Empathy is one of the basic qualities that modern clinicians need to possess.Although traditional Chinese medicine has no definition for empathy,it does have practical applications.TCM clinical empathy,nurtured by Chinese excellent traditional culture,can be seen in TCM classics and clinical practice of famous doctors of previous generations,and has been inherited in the spiritual thinking of modern colleges and universities of Chinese medicine.However,at present,there is a relative lack of special training courses for"empathy"in Chinese medicine higher education.This paper first briefly describes the connotation,history,and neuroscience mechanism of the concept of"empathy".Secondly,the manifestations and characteristics of"empathy"in the clinical practice of traditional Chinese medicine were sorted out.Finally,we use modern medicine and psychology for reference,and combine the characteristics of traditional Chinese medicine to make suggestions for the cultivation of the ability of"empathy"in clinical Chinese medicine.

Autoimmune gastritis is a chronic progressive inflammatory disorder associated with diverse comorbidities and complications,of which early detection and effective intervention remain challenging.This review provides a comprehensive insight into advances of research on autoimmune gastritis in pathogenesis,clinical features,diagnosis and treatment,in order to establish appropriate management strategies.

Objective:To investigate an accurate and quantitative method to measure the eyeball morphological parameters of guinea pigs through a method that combines programmed digital techniques and mathematical geometric principles.Methods:Twenty-two three-week-old clean-grade male tricolor guinea pigs were selected and sacrificed by anesthesia overdose.Eyeballs were enucleated.The horizontal and sagittal images of the eyeball were taken with the high-speed photographic model of 13 million pixels macro meter, and the pictures were imported into pycharm programming software.Using the pre-written analysis program of Python 3.9, the conversion coefficient between the photo pixel and the actual length was obtained by a scale, and then the corneal surface was fitted by arc fitting and conic curve fitting.The results of arc fitting were converted to calculate the corneal radius of curvature.The corneal eccentricity was calculated according to the general conic equation (Ax 2+ Bxy+ Cy 2+ Dx+ Ey+ F=0). The corneal asphericity was evaluated by curve fitting between the central 3-mm and the whole cornea.The use and care of the animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Shanghai Public Health Clinical Center (No.2022-A009-01). Results:The digital method of Python programming can show the corneal contour of guinea pigs completely and clearly.In the transverse plane, there was no significant difference in the corneal curvature measurements among the digital fitting in central 3-mm cornea, digital fitting in whole cornea and curvature meter ( F=1.693, P=0.190). In the sagittal plane, there was a significant difference in the corneal curvature measurements among the three methods ( F=3.500, P=0.030), and the corneal curvature measurements of the whole cornea measured by the curvature meter were significantly greater than those measured by the digital fitting ( P<0.05). There was no statistical significance in the measurements of corneal curvature radius among the three methods in the transverse plane and the sagittal plane ( F=1.817, P=0.170; F=2.050, P=0.133). The horizontal and sagittal corneal eccentricity measured by digital fitting in central 3-mm cornea were 0.55±0.15 and 0.53±0.17, which were lower than 0.66±0.10 and 0.64±0.14 measured by digital fitting in whole cornea, and the differences were statistically significant ( t=-4.860, -5.210; both at P<0.01). Conclusions:It is feasible to use Python programming digital method to measure the corneal curvature and eccentricity of guinea pigs.