Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective:To summarize the concept, theoretical basis, evaluation tools and mechanisms, influencing factors, and intervention measures of kinesiophobia.Methods:The literature on kinesiophobia in patients undergoing total knee replacement was electronically searched on databases such as China National Knowledge Infrastructure, China Biology Medicine disc, WanFang Data, PubMed, CINAHL, Web of Science, Embase, Scopus, PsycINFO, Cochrane Library. The search period was from database establishment to June 24, 2023. This study extracted and analyzed data from the included literature.Results:A total of 32 articles were included. The Tampa Scale for Kinesiophobia was a widely used tool for evaluating kinesiophobia. The influencing factors of kinesiophobia were demographic and disease factors, body motor function, and psychological and social factors. The intervention measures for kinesiophobia mainly included cognitive behavioral intervention, pain health education, exercise, art video or music intervention, multidisciplinary collaborative intervention, and so on.Conclusions:The concept and theoretical basis of kinesiophobia are not yet complete. It is necessary to revise and improve the theoretical model and assessment tool for kinesiophobia and construct an intervention program for kinesiophobia in combination with the concept of rapid rehabilitation.

Objective To establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

Small cell lung cancer (SCLC) is a rapidly developing malignant tumor, which is highly heterogeneous and prone to drug resistance, and the prognosis is usually poor. Poly ADP-ribose polymerase (PARP) inhibitors target the DNA damage response pathway, preventing DNA repair, thereby exerting anti-tumor effects. Currently, PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited, it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC.

Objective: To investigate the effects of lactoprotein iron chelates on rats with iron deficiency anaemia (IDA), so as to provide insights into developing and utilizing novel iron supplements. Methods: Seventy weaning female SPF-graded rats of the SD strain were randomly divided into the control group (A), model group (B), ferrous sulfate group (C), lactoferrin group (D), lactoferrin iron chelate group (E), Casein oligopeptide iron chelate group (F) and whey protein oligopeptide iron chelate group (G), with 10 rats in each group. The rats in group A were fed with normal diet, and the others were fed with poor iron diet for IDA modeling. The corresponding interventions were given by intragastric administration once a day. The iron ion concentrations of group C, E, F and G were 2.0 mg/kg, and the protein and oligopeptide concentrations of group D, E, F and G were 2 000 mg/kg. Body weight and hemoglobin of rats were measured weekly during 21-day intervention. At the end, peripheral blood samples were collected, and blood routine, iron metabolism and liver function indicators were determined. Results: After the intervention, among blood routine indicators, the rats in group C, E, F and G showed elevated hemoglobin, red blood cell, mean corpuscular volume and hematocrit, and decreased free protoporphyrin and mean corpuscular hemoglobin concentration when compared with the rats in group B (all P<0.05); among iron metabolism indicators, the rats in group C, E and G showed elevated serum ferritin, the rats in group C, E, F and G showed elevated serum iron, the rats in group C, D, E, F and G showed decreased unsaturated iron binding capacity and total iron binding capacity when compared with the rats in group B (all P<0.05); among liver function indicators, the rats in group E and G showed decreased alanine transaminase when compared with the rats in group B (both P<0.05). Conclusions Lactoprotein alone could not completely improve IDA in rats compared with traditional iron supplement (ferrous sulfate). Lactoprotein iron chelate, especially whey protein oligopeptide iron chelate, could significantly improve IDA, iron reserve and liver function damage in rats.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10^-3 g·kg^-1·（3 d）^-1］， Shenqi Yiliu prescription group （27 g·kg^-1·d^-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Objective:To evaluate the effect of propofol on neuronal activity in medial prefrontal cortex (mPFC) during social behavior in sleep-deprived rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (CSD+ Pro). Sleep deprivation model was developed by the modified multiple platform method, and the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00) and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days.Propofol 40 mg/kg was intraperitoneally injected after sleep deprivation for 28 consecutive days in group CSD+ Pro, while the equal volume of 10% fat emulsion was given instead in group C and group CSD+ NS.Electroencephalographic recordings in cerebral cortical regions were performed on the days 1st, 14th and 28th after sleep deprivation.The apoptotic neurons in mPFC were detected using TUNEL method after the end of sleep deprivation, and the apoptosis index was calculated.A three chamber sociability test was used to detect the social behavior of rats, and local field potential signals in mPFC were collected. Results:Compared with group Con, the percentage of rapid eye movement sleep was significantly increased, the sniffing time preference coefficients in the 2 stages were reduced, the percentage of the β waves and θ waves-band power in mPFC during the social sniffing process was decreased, and the apoptosis index of neurons in mPFC was increased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the percentage of rapid eye movement sleep was significantly increased, the sniffing time preference coefficient in the 2 stages was increased, and the percentage of β waves and θ waves-band power in mPFC during the social sniffing process was increased, and the apoptosis index of neurons in mPFC was decreased in group CSD+ Pro ( P<0.05). Conclusions:Propofol inhibits the apoptosis in neurons in mPFC and increases β and θ waves in the mPFC during social interaction after sleep deprivation in sleep-deprived rats, which is helpful in improving sleep deprivation-induced social disorder.

Objective To observe the expression level of insulin-like growth factor-1 receptor (IGF-1R) in the cartilage tissue of children with Kaschin-Beck disease (KBD) and T-2 toxin-poisoned rats under low selenium condition,and the effect of IGF-1R inhibitor on apoptosis of human normal chondrocytes (C28/I2 cells),and to investigate the role of IGF-1R in the pathogenesis of KBD.Methods The knuckles of dead children (5 cases) in the KBD areas,car accident death and congenital 6 finger deformity operation children (5 cases) in non-KBD areas in Shaanxi were collected,the expression of IGF-1R in the articular cartilage was detected by immunohistochemistry.Thirty-two male Sprague-Dawley rats with a body mass of 60-80 g were selected,according to the body mass,they were divided into the routine feed group (selenium content:101.5 μg/kg) and the low-selenium feed group (selenium content:1.1 μg/kg) by random number table method,16 rats in each group.After 30 days of feeding,the routine feed group was divided into control group and T-2 toxin group (100 ng·kg-1·d-1),the low-selenium feed group was divided into low selenium group and low selenium + T-2 toxin group,8 rats in each group,the expression of IGF-1R in the articular cartilage of the left knee joint was detected by immunohistochemistry after 30 days of feeding.C28/I2 cells were cultured in vitro and treated with T-2 toxin 0 (control),6,12,and 24 μg/L,and each concentration of T-2 toxin was accompanied with sodium selenite (+ 0.1 mg/L) for 72 h.Meanwhile,IGF-1R inhibitor with 0 (control),250,500,and 1 000 μg/L was treated on C28/I2 cells for 48 h.The expression levels of IGF-1R mRNA and protein in chondrocytes were detected by Real-time PCR and Western blotting,and the apoptosis of chondrocytes was detected by flow cytometry.Results Compared with the control group [(100.00 ± 0.00)％,(100.00 ± 0.00)％],the expression rates of IGF-1R positive cells in articular cartilage surface and middle layers [(72.71 ± 4.75)％,(36.33 ± 4.32)％] of children in KBD group were significantly reduced (t =12.852,32.650,P ＜ 0.01).Compared with control group [(100.00 ± 0.00)％,(100.00 ± 0.00)％,(100.00 ± 0.00)％],the expression rates of IGF-1R positive cells in articular cartilage middle layer [(20.83 ± 2.69)％,(26.45 ± 2.84)％,(20.34 ± 1.82)％],deep layer [(33.55 ± 5.66)％,(48.89 ± 8.39)％,(25.51 ± 7.50)％],and the expression rates of IGF-1R positive cells [(47.50 ± 1.47)％,(28.66 ± 3.58)％,(40.52 ± 6.78)％] in the hypertrophic layer of the metaphyseal plate of rats in low selenium,T-2 toxin,and low selenium + T-2 toxin groups were significantly reduced (P ＜ 0.01).C28/I2 cells were cultured in vitro,compared with the control group,IGF-1R mRNA and protein expression levels in each T-2 toxin groups were significantly reduced (P ＜ 0.05).The expression levels of IGF-1R mRNA (1.95 ± 0.35,2.44 ± 0.17,2.40 ± 0.15) in 6,12,24 μg/L T-2 toxin + 0.1 mg/L selenium groups were significantly higher than those in T-2 toxin groups (0.80 ± 0.08,0.63 ± 0.08,0.61 ± 0.11,t =-12.259,-11.279,-13.371,P＜ 0.05).The expression levels of IGF-1R protein (1.67 ± 0.70,1.07 ± 0.26) in 6,12 μg/L T-2 toxin + 0.1 mg/L selenium groups were significantly higher than those in T-2 toxin groups (0.52 ± 0.05,0.72 ± 0.05,t =-25.977,-10.776,P ＜ 0.05).Compared with the control group [(5.33 ± 0.85)％,(4.03 ± 1.15)％],C28/I2 cells early apoptosis rates [(8.26 ± 1.51)％,(13.00 ± 0.72)％,(13.19 ± 1.05)％] in each of IGF-1R inhibitor groups,and late apoptosis rates [(8.50 ± 0.71)％,(14.21 ± 1.10)％] in 500,1 000 μg/L IGF-1R inhibitor groups were increased significantly (P ＜ 0.05).Conclusions The expressions of IGF-1R in the cartilage tissue of KBD children and T-2 toxin-poisoned rats under low selenium condition are decreased.T-2 toxin decreases the expression of IGF-1R in chondrocytes,and selenium can partly inhibit the effect of T-2 toxin on IGF-1R.Down-regulation of IGF-1R causes chondrocyte apoptosis,and it may play an important role in KBD chondrocyte apoptosis.