ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

Objective:To explore the effects of lower concentrations of ropivacaine on ultrasound-guided nerve block in pediatric orthopedic surgery.Methods:Using a retrospective study method, 75 children who underwent orthopedic surgery at Wu Jiang District Children′s Hospital from May 2023 to February 2024 were selected and divided into Group A (25 cases, 0.15% ropivacaine nerve block), Group B (25 cases, 0.20% ropivacaine nerve block) and Group C (25 cases, 0.25% ropivacaine nerve block). The heart rate; mean arterial pressure; onset time of anesthesia; analgesic maintenance time; recovery time of movement and sensation; child face, legs, activity, cry, consolability behavioral tool (FLACC) score at 2 h after surgery; adverse reactions incidence of postoperative local anesthetic drugs were compared.Results:There was no statistically significant difference in the physical indicators of heart rate and mean arterial pressure among the three groups ( P>0.05). As the concentration of ropivacaine increased, the onset time of anesthesia in the three groups of children was shortened: (11.04 ± 1.02) vs. (10.44 ± 1.04) and (7.16 ± 0.85) min, and the differences between the three groups were statistically significant ( P<0.05); There was no statistically significant difference in the analgesic maintenance time among the three groups ( P>0.05). As the concentration of ropivacaine increased, the recovery time of movement and sensation was increased: (194.64 ± 20.43) min vs. (207.72 ± 22.34) and (250.32 ± 30.18) min, (176.44 ± 16.18) min vs. (189.24 ± 20.66) and (224.08±29.56) min, and the differences among the three groups were statistically significant ( P<0.05). There was no statistically significant difference in FLACC scores among the three groups of patients at 2 h after surgery ( P>0.05). The total incidence of adverse reactions in Group A was lower than that in Groups B and C: 4% (1/25) vs. 24% (6/25) and 52% (13/25), and the differences among the three groups were statistically significant ( P<0.05). Conclusions:The 0.15% ropivacaine used for ultrasound-guided nerve block in pediatric orthopedic surgery can achieve good anesthesia effects with low incidence of adverse reactions, and is worthy of clinical promotion.

Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

OBJECTIVE: To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism. METHODS: An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg^-1 · min^-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits. RESULTS: The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression. CONCLUSION Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.
Animals ; Mice ; Angiotensin II ; Tumor Suppressor Protein p53 ; Acetylation ; Stroke Volume ; Ventricular Remodeling ; Ventricular Function, Left ; Myocytes, Cardiac

Objective:To investigate the long-term alcohol consumption on synaptic plasticity of mossy fiber-granule cells in cerebellar cortex and motor coordination function in mice.Methods:Thirty healthy male ICR mice aged 6-8 weeks were divided into saline group (control group)and alcohol consumption group(alcohol group) according to random number table with 15 in each group. The mice in alcohol group were injected intraperitoneally with 15% ethanol (1.6 g/kg), while the mice in control group were injected with the same volum of normal saline, all mice were injected intraperitoneally once a day for 28 consecutive days. Walking obstacle test and rotating rod fatigue test were used to observe the motor coordination ability and learning ability of mice. Electrophysiological patch clamp technique was used to detect the field potential changes of long-term synaptic plasticity induced by blowing stimulation. SPSS 22.0 software was used for statistical analysis.Independent sample t-test, paired t-test and repeated measurement analysis of variance were used for comparison between the two groups before and after intervention. Results:The electrophysiological results showed that the amplitude percentage of field potential N1 wave in the control group after blowing stimulation was (130.4±3.3)%, which was higher than that before stimulation ((100.6±2.7)%) ( t=27.07, P<0.01). And the percentage of area under N1 standardized waveform after stimulation ((128.8±4.5)%) was greater than that before stimulation ((100.2±3.5)%) ( t=19.43, P<0.01). There was no significant difference in the amplitude percentage of N1 wave in alcohol group ((97.8±4.3)%) after blowing stimulation compared with that before stimulation ((99.5±5.6)%) ( t=0.93, P>0.05). And also there was no significant difference in the area percentage under N1 wave after stimulation ((96.8±3.6)%) compared with that before stimulation ((100.2±4.2)%) ( t=2.38, P>0.05). The results of walking obstacle test showed that the total number of errors (3.14±0.19) in the alcohol group was higher than that in the control group(1.52±0.29) ( t=17.87, P<0.01), and the total error time ((63.85±9.34) ms) was longer than that in the control group ((28.93±7.21) ms) ( t=11.45, P<0.01). The results of repeated measurement analysis of variance showed that there was an interaction between time and group in the falling speed and falling latency of the two groups of mice in the rotating rod fatigue experiment ( F=4.5, 455.1, both P<0.05). The drop speed of mice in the alcohol group was significantly lower than that in the control group from day 1 to 7 (all P<0.05). The fall latency of mice in the alcohol group from day 1 to 7 was shorter than that in the control group, and the difference was statistically significant (all P<0.05). Conclusion:Long-term alcohol consumption impairs synaptic plasticity in the granular layer of mice and leads to a significant decline in motor coordination and motor learning ability.

Objective:To evaluate the effect of Activin-A on spinal inflammatory response in rats with incisional pain and the relationship with p38 mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, aged 1 month, weighing 100-150 g, were divided into 4 groups ( n=12 each) by the random number table method: sham operation group (S group), incisional pain group (I group), sham operation + antagonist group (SA group) and incisional pain + antagonist group (IA group). The rat model of incisional pain was prepared in group I and group IA.At the first 30 min of model preparation, the antagonist follicle statin 5 μg/kg was intraperitoneally injected in SA and IA groups, and the normal saline 5 μg/kg was intraperitoneally injected in S and I groups.At 24 h before model preparation (T 0) and 2, 6 and 24 h after model preparation (T 1-3), 3 rats in each group were randomly selected to measure the thermal paw withdrawal latency (TWL). Then 3 rats in each group were randomly sacrificed, and the spinal cord L 4-6 segments were taken for determination of the expression of Activin-A and p38 MAPK mRNA (by quantitative real-time polymerase chain reaction) and contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β (by enzyme-linked immunosorbent assay). Results:Compared with group S, the TWL was significantly shortened, the contents of TNF-α and IL-1β were increased, and the expression of Activin-A and p38 MAPK mRNA was up-regulated at T 1-3 in I and IA groups ( P<0.05), and no significant change was found in each parameter in group SA ( P>0.05). Compared with group SA, the TWL was significantly shortened, the contents of TNF-α and IL-1β were increased, and the expression of Activin-A and p38 MAPK mRNA was up-regulated at T 1-3 in I and IA groups ( P<0.05). Compared with group I, the TWL was significantly prolonged, the contents of TNF-α and IL-1β were decreased, and the expression of Activin-A and p38 MAPK mRNA was down-regulated at T 1-3 in group IA ( P<0.05). Conclusions:Activin-A is involved in spinal inflammatory response through activating the p38 MAPK signaling pathway in rats with incisional pain.

Objective : To develop an extracellular vesicles ( EVs) co⁃loading system by synergistically deliver tumor necrosis factor related apoptosis inducing ligand (TRAIL) /verteporfin (VPF) combination to induce apoptosis and inhibit proliferation of OSCC cells . Methods : TRAIL/VPF co⁃loaded EVs (MSCT⁃EVs/VPF) was purified and collected though ultracentrifugation and dialysis . The expression of CD63 , CD9 and TRAIL was detected by BCA to confirm the origin of EVs . High performance liquid chromatography (HPLC) was used to detect the drug loading of VPF and draw the release curve in vitro . Cytotoxicity and half inhibitory concentration (IC50 ) were detected by MTT assay . The apoptosis rate was detected by flow cytometry . Finally , Western blot was used to detect the effects of MSCT⁃EVs/VPF on the expression of apoptosis related proteins and Yap in SCC25 cells . Results: MSCT⁃EVs/VPF particles were round and well dispersed with a diameter of about 100 nm . The drug loading of the nano system was about ( 15 . 43 ± 0. 44)% , 57. 8% of VPF was released in 10 h and 82. 5% in 45h ; MSCT⁃EVs and VPF could inhibit the growth of SCC25 tumor cells in a dose⁃depe~ndent manner , showing good synergistic effect in the ratio of 10 : 1 - 5 : 1 ( CI < 1 , wt% ) . At the ratio of 100 : 5 100 : 15 ( Mass ratio of MSCT⁃EVs to VPF , wt% ) , the IC50 of MSCT⁃EVs/VPF was significantly lower than that of free MSCT⁃EVs + free VPF group (P < 0. 05) , and showed a more effective inhibition . The high inhibitory effect of MSCT⁃EVs/VPF on squamous cell car cinoma cells was partly due to the regulation of Caspase⁃3 , Bax , BCL⁃2 , mTOR , p ⁃mTOR and YAP . Conclusion EVs delivery of a fixed proportion of TRAIL/VPF shows high inhibitory effect on oral squamous cell carcinoma cells , which provides a new idea for the treatment of multidrug⁃resistant tumors .

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. It mainly occurs in young and middle-aged people and has a high disability rate. The pathogenesis of MS has not been fully elucidated, with great genetic heterogeneity, diverse clinical phenotypes, lack of specific biomarkers, numerous and complicated research data, which bring great challenges to the diagnosis and treatment of MS. Artificial intelligence (AI), as the cutting-edge hotspot in the development of science and technology, is widely used in the medical field to assist in the diagnosis, treatment and prognosis of various diseases. Its infinite learning ability greatly promotes the management of MS. This article will review the application of AI in MS diagnosis and treatment.

Objective: To understand the knowledge, attitude and behavior of HIV/AIDS prevention and treatment of freshmen in Jiangsu Colleges, so as to provide evidence for carrying out HIV/AIDS prevention and treatment propaganda among young college students. Methods: A total of 2 538 freshmen in 8 colleges in Jiangsu province were surveyed by cluster sampling, and anonymous self-reported questionnaire survey was carried out. Valid questionnaires were collected and analyzed. Results: Among 2 538 students valid, the total awareness rate of the eight items of new HIV/AIDS basic knowledge which provided to the public by the State (referred to the new eight items) was 85.74%, the awareness rate of boys was higher than that of girls’(88.21%, 84.34%)(P<0.05), the rate of college students of science was higher that of those of arts(87.31%, 83.67%)(P<0.05). the general awareness rate of other knowledge was 72.14%, and the rate of boys was higher than that of girls(75.00%, 70.53%)(P<0.05). As for "whether eating with the AIDS-affected patients may be affected with AIDS/HIV", boys and students of science were more rational(58.3%, 55.1%; 50.4%, 50.9%)(P<0.05). 50.08% students approved of having sexual behavior before marriage, and the rate of boys was higher than that of girls(69.00%, 39.40%)(P<0.01). 71.24% of the students thought that condoms should be used consistently in sex behaviors, and the proportion of female students (80.76%) was much higher than that of male students(54.37%), and the rate of the students of science was higher than that of students of arts(73.36%, 69.63%)(P<0.05). 6.03% students had received consult and test of AIDS. 40.34% of the untested students were willing to receive the test but didn’t know where to go. 1.34% students were afraid of receiving the test because of fear. The most popular ways of HIV/AIDS publicity among students are micro films(76.32%), lectures(66.67%) and peer education(60.80%). Conclusion It is suggested to publicize HIV/AIDS knowledge among students according to different gender and subject characteristics and combining multimedia, with emphasis on strengthening the publicity of HIV/AIDS epidemiology,treatment and related information, and attaching importance to sexual health education among young students.

OBJECTIVE：To evaluate th e eff ects of infusion sequence regulation on the promotion of intravenous rational drug use. METHODS ：The intelligent control of infusion sequence was realized with Markov chain machine learning method on the basis of intelligent reminder manual labeling infusion sequence. Selected from Binhu Hospital of Hefei during Jan. to Sept. 2017， 164 800 inpatients’medication orders were collected as data before intelligent control of infusion sequence ，and 264 600 inpatients’ medication orders were collected as data after intelligent control of infusion sequence. The correct rate of incompatibility ，storage time limit ，administration frequency ，chronopharmacology，preventive drugs ，drug interaction ，auxiliary drugs and infusion sequence for intravenous irritant drugs were compared before and after regulation ；the times of flushing tube ，the cost of flushing tube infusion and the change of liquid property in the infusion tube were compared before and after regulation. RESULTS ：The correct rate of incompatibility ，storage time limit ，administration frequency ，chronopharmacology，drug interaction and infusion sequence for auxiliary drugs after regulation were significantly higher than before regulation ；the correct rate of infusion sequence for preventive drugs and intravenous irritant drugs ，the times of flushing tube ，the cost of flushing tube infusion and the case number of the liquid change （proportion） in infusion tube were significantly lower than before regulation （P＜0.001）. CONCLUSIONS：Intelligent regulation of infusion sequence can improve the rationality of intravenous medication sequence to a certain extend.