ObjectiveTo investigate the efficacy and mechanism of saffron floral bio-residues（SFB） in the treatment of hyperuricemia（HUA） combined with gouty arthritis（GA） in a compound compatibility setting. MethodScreening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis. After adaptive feeding of 80 SD rats for 7 days， 10 rats were randomly selected as the blank group， while the remaining 70 rats were intraperitoneally injected with 3% potassium oxonate and orally administered with 1% adenine for 14 consecutive days. On the 13^th day， rats were injected with 2.5% sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side， inducing a HUA combined with GA model. At the same time， the modeling rats were randomly divided into 7 groups， including the model group， benzbromarone group（positive drug， 0.02 g·kg^-1）， Tongfengshu tablets group（9 g·kg^-1）， Tongfengshu granules group（9 g·kg^-1）， SFB granules group（3.6 g·kg^-1）， Plantaginis Semen granules group（3.6 g·kg^-1）， and new formula group（SFB replacing Plantaginis Semen in Tongfengshu granules， 9 g·kg^-1）， with 10 rats in each group. Each treatment group was orally administered with the corresponding drugs according to body weight， while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days. After 14 days of synchronous administration and modeling， changes in gait， ankle joint swelling and mechanical pain threshold in rats were observed， and serum uric acid， creatinine， urea nitrogen and xanthine oxidase（XOD） were measured. Enzyme-linked immunosorbent assay（ELSIA） was used to detect the levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β and IL-6 in rat serum， hematoxylin-eosin（HE） staining was used to observe the pathological changes in the liver， kidney and ankle joints of rats， Western blot was used to detect the expression levels of uric acid transporter 1（URAT1）， glucose transporter 9 （GLUT9）， organic anion transporter 1（OAT1）， adenosine triphosphate（ATP） binding cassette transporter G2（ABCG2）， and liver XOD proteins. ResultThrough network pharmacology analysis， Plantaginis Semen was selected as a candidate control herb， and Tongfengshu tablets was used as a compound compatibility environment to explore the efficacy of SFB in reducing blood uric acid levels and treating GA. Animal experiments showed that compared with the blank group， the gait score and joint swelling degree of the model group were significantly increased， and the mechanical pain threshold was significantly decreased（P<0.01）. Compared with the model group， the gait score， joint swelling degree and mechanical pain threshold of rats in each medication group were improved to varying degrees. Biochemical indicators showed that compared with the blank group， the serum uric acid， creatinine， urea nitrogen and XOD levels of the model group were significantly increased（P<0.01）. Compared with the model group， the serum uric acid and XOD levels of rats in each treatment group were significantly decreased（P<0.01）. ELISA results showed that compared with the blank group， the levels of serum TNF-α， IL-1β and IL-6 in the model group were significantly increased（P<0.01）. Compared with the model group， the levels of TNF-α， IL-1β and IL-6 in the benzbromarone group， Tongfengshu tablets group， Tongfengshu granules group and new formula group were significantly reduced（P<0.05，P<0.01）. Western blot results showed that compared with the blank group， the expression levels of URAT1 and GLUT9 proteins in renal tissue and OXD protein in liver tissue of the model group were significantly increased， while the expression levels of renal OAT1 and ABCG2 were significantly decreased（P<0.01）. Compared with the model group， the expression levels of renal URAT1 and GLUT9 in the SFB granules group， Tongfengshu granules group and new formula group were significantly decreased， while the expression levels of renal OAT1 and ABCG2 were significantly increased， and the expression of XOD protein in liver tissue was significantly decreased（P<0.05， P<0.01）. Pathological analysis showed that focal infiltration of neutrophils， cell necrosis and nuclear fragmentation were observed in the liver tissue of the model group， sodium urate deposition crystals and tubular dilation appeared in renal tissue， synovial hyperplasia and inflammatory cell infiltration appeared in ankle joint. Compared with the model group， the abnormal degrees of liver， kidney and ankle joint tissue of rats in each treatment group were alleviated. ConclusionThe new formula of SFB replacing Plantaginis Semen has the same effect in the treatment of HUA combined with GA. This study proposes a new strategy to investigate the efficacy of new resources of Chinese medicine in a compound compatibility environment， which can provide a new demonstration for the research and development of new resources of Chinese medicine.

Among the current curricula of medical teaching in China, most courses focus on the integrated teaching of a single organ-system combination, while there are relatively a few integrated courses that focus on the multiple dimensions between different organs and systems and between medical sciences and social sciences. In 2016, Chongqing Medical University started to cooperate with University of Leicester to establish the clinical medicine major and introduced the course of Integration for Clinical Application (ICA) that had been run well in University of Leicester for years. With reference to the education goal of our university, the curriculum group adopted a series of actions for the localization of this course from the aspects of teaching objectives, contents, teaching model, education resources, and quality of faculty. After the completion of the first round of this course, the passing rate reached 86.96%(100/115) in the quantified evaluation of accomplishment, which was higher than the passing rate of other courses introduced from University of Leicester. The quantitative expert assessment of this course also ranked among the top courses in our university, and student assessment showed that the ability indicators were improved by 25.00%- 38.00%. The above data show that good results have been achieved for the curriculum localization of ICA.

Objective To investigate the equivalent conversion of head injury criterion(HIC)under anterior-posterior(AP)and lateral-medial(LM)craniocerebral impact for mild craniocerebral injury in rats using motor evoked potential(MEP)and β-amyloid precursor protein(β-APP)immunohistochemistry(IHC).Methods Sixty healthy adult male SD rats were randomly divided into 0 m control group,0.5 m-AP and 0.5 m-LM injury groups,and 1 m-AP and 1 m-LM injury groups(12 rats in each group).The control group did not undergo any impact injury experiment.After the impact injury experiment,the injury and control groups were subjected to excessive anesthesia to produce β-APP immunohistochemical stained slices,and the percentage of positive area and integral optical density(IOD)in the brainstem pyramidal tract area of the slices were determined.The MEP groups were divided in the same manner as the IHC groups and the MEP amplitudes of the MEP and control groups were measured after the impact injury experiment.Results With an increase in the degree of injury,the decrease in MEP amplitude,percentage of positive areas,and IOD in the injury groups significantly increased.When the degree of injury was low,the sensitivity of IHC was higher than that of MEP.When the degree of injury was the same,the HIC in the LM direction was lower than that in the AP direction.When the HIC was the same,the degree of injury in the LM direction was greater than that in the AP direction.Conclusions The joint evaluation of MEP and β-APP can provide experimental references for the study of HIC equivalent conversion in AP-LM craniocerebral impact injury.

Objective:To evaluate the clinical application of water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation for critical patients.Methods:This study was a randomized controlled trial. Eighty patients who needed indwelling nasobenteric tube were selected from June 2021 to April 2022 in the Department of Critical Care Medicine, Xiangya Hospital, Central South University. They were divided into control group ( n=40) and experimental group ( n=40) by systemic randomization. For the patients in the experimental group, the intubation was performed by water-filling with "four-eyes" sign under the guidance of ultrasound. For the control group, the traditional method was applicated under the guidance of ultrasound. Using abdominal X-ray as the gold standard of successful pylorus posterior catheterization, the result of catheterization, time of operation, efficiency of positioning in the two groups were analyzed and compared. Results:In the experimental group, 38 cases were successfully intubated, 2 were failed; in the control group, 27 cases were successfully intubated, 13 were failed, and all the failed cases in the control group were then successfully intubated again by using method of the experimental group. The success rate of tube placement in the experimental group was 95.0% (38/40), which was higher than 67.5% (27/40) in the control group ( χ2 = 9.93, P<0.05). The average time of operation in the experimental group was (45.2 ± 14.2) min, which was significantly lower than (70.2 ± 17.7) min in the control group, the difference was significantly different ( t=-5.51, P<0.05). The specificity, sensitivity, positive predictive value, negative predictive value and diagnostic rate of nasal-jejunum intubation positioning in the experimental group were 100.0% respectively, higher than 38.4%, 77.7%, 72.4%, 45.4%, 65.0% in the control group; the false positive rate, false negative rate in the experimental group were both 0, lower than 22.2%, 61.5% in the control group, with statistically significant differences( χ2 values were 4.69- 16.97, all P<0.05). Conclusions:Water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation was a new method which can shorten the operation time and increase the success rate for intubation. It has relatively high positioning accuracy and possess valuable clinical application.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

OBJECTIVE: To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC). METHODS: A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO₂), oxygen consumption (VO₂) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups. RESULTS: Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO₂ and SV were significantly increased [DO₂ (mL×min^-1×m^-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L^-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ² = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ² = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO₂ factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042]. CONCLUSIONS dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.
Adult ; Humans ; Prospective Studies ; Ventricular Pressure ; Sepsis/complications* ; Shock, Septic/drug therapy* ; Cardiomyopathies/etiology* ; Prognosis

OBJECTIVE To establish the fingerprint of Shenfukang Ⅱ capsule(SC-Ⅱ), and to screen out its indicative compounds for quality control combined with chemometrics methods and network pharmacology. METHODS The HPLC fingerprint of 10 batches of SC-Ⅱ was established, and similarity evaluation was analyzed by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 A Edition) to determine common peaks; common peaks were identified through standard comparison. Chemometrics methods was used to evaluate quality of 10 batches of SC-Ⅱ, and network pharmacology was used to screen out core targets and pathways of SC-Ⅱ. Combined with the above results, indicative compounds for quality control of SC-Ⅱ were screened out. RESULTS A total of 37 common peaks were obtained in the HPLC fingerprint, the similarity of samples was greater than 0.97. Twenty compounds were identified as morroniside, loganin, paeoniflorin and et al. The samples were divided into two categories by chemical pattern recognition, salvianolic acid B, morroniside, salvianolic acid A and paeoniflorin were differential marker compounds for SC-Ⅱ. Network pharmacology predicted that active compounds such as salvianolic acid B, paeoniflorin and morroniside might exert pharmacological effects through 45 core targets and 15 main pathways. The research preliminary preliminarily predicted that morroniside, paeoniflorin and salvianolic acid B were quality control index components for SC-II. CONCLUSION The established HPLC fingerprint method is simple and good repeatability. The quality control indicative compounds of SC-Ⅱ can provide a basis for its quality control.

Objective:To evaluate the role of N-methyl-D-aspartate receptors (NMDA receptors) in sevoflurane anesthesia-caused necroptosis in hippocampal neurons of aged mice.Methods:Ninety clean-grade healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were divided into 3 groups ( n=30 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and sevoflurane anesthesia plus NMDA receptor antagonist memantine hydrochloride group (group S+ M). Mice inhaled 3% sevoflurane for 2 h for 3 consecutive days in S group and S+ M group, and memantine hydrochloride 20 mg/kg was intraperitoneally injected at 1 h before each inhalation of sevoflurane in S+ M group.Mice only inhaled pure oxygen for 2 h in group C. Ten mice of each group were selected on 1 day before anesthesia and 3 and 7 days after anesthesia to perform Morris water maze test.The mice were sacrificed immediately after Morris water maze test, and hippocampus was removed for microscopic examination of pathological changes (with a light microscope) and for determination of the necroptosis rate of neurons and cytoplasmic free calcium concentration([Ca 2+ ] i)(by flow cytometry), and expression of NMDA receptor subtypes GluN2A, GluN2B and receptor-interacting protein kinase 1 (RIP1) (by Western blot). Results:Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were increased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was up-regulated( P<0.05), and the pathologic changes were accentuated in S group and S+ M group.Compared with group S, the escape latency was significantly shortened, and the frequency of crossing the original platform was increased, and the [Ca 2+ ] i and neuronal necroptosis rate in the hippocampus were decreased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was down-regulated ( P<0.05), and the pathologic changes were attenuated in group S+ M. Conclusions:NMDA receptors are involved in the process of cognitive dysfunction induced by sevoflurane anesthesia in aged mice, and the mechanism may be related to the promotion of necrptosis in hippocampal neurons.

Objective:To evaluate the role of RhoA/ROCK2 signaling pathway in multiple exposures to sevoflurane-induced long-term cognitive impairment in neonatal rats.Methods:Sixty SPF healthy neonatal Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple exposures to sevoflurane group (group S) and RhoA/ROCK2 signaling pathway inhibitor Y-27632 group (group Y). Group S and group Y inhaled 3% sevoflurane for 2 h at days 6, 7 and 8 after birth.In group Y, Y-27632 5 mg/kg was intraperitoneally injected before sevoflurane anesthesia.The spontaneous activity was evaluated by open field test on day 35 after birth.The cognitive function was detected by Morris water maze test at day 36 after birth.The rats were sacrificed after Morris water maze test, and the hippocampal tissues were isolated for determination of the apoptosis rate of hippocampal neurons and cytoplasmic calcium concentration ([Ca 2+ ] i) (by flow cytometry) and expression of phosphorylated RhoA (p-RhoA), ROCK2 and cleaved-caspase-3 (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no significant difference in movement speed, distance and time of stay in the open field center in the open field test among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal neurons and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological injury to hippocampal neurons was found in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, the apoptosis rate of hippocampal neurons and [Ca 2+ ] i were decreased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was down-regulated ( P<0.05), and the pathological injury to hippocampal neurons was attenuated in group Y. Conclusions:The mechanism by which multiple exposures to sevoflurane induces long-term cognitive impairment is related to activation of RhoA/Rock2 signaling pathway and induction of apoptosis rate of hippocampal neurons in neonatal rats.

OBJECTIVE To develop an HPLC method for the simultaneous dete rmination of morroniside ，loganin，paeoniflorin， salvianolic acid B and icariin in Shenfukang Ⅱ capsule. METHODS The determination was performed on Agilent 5 TC-C18 column with mobile phase consisted of acetonitrile- 0.1％ phosphate acid （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃，and detection wavelength was set at 240 nm. The sample size was 10 μL. RESULTS The linear range of morroniside，loganin，paeoniflorin，salvianolic acid B and icariin were 4.80-240.00，4.84-242.00，7.00-350.00，4.72-236.00 and 5.18-259.00 μg/mL（r≥0.999 8），respectively. RSDs of precision ，stability and reproducibility tests were all lower than 3％（n＝6）. Average recoveries were 97.22％-101.36％ with the RSDs of 1.19％-2.43％（n＝6）. The contents of above 5 components in 5 batches of samples were 2.019 3-2.360 0，1.624 2-1.847 1，5.637 7-6.828 0，5.015 9-5.717 0 and 1.208 8-1.754 6 mg/g，respectively. CONCLUSIONS The method is simple ，accurate and reproducible. It can improve the quality control level of Shenfukang Ⅱ capsule.