ObjectiveTo study the effect and mechanism of Shentong Zhuyutang in treating intervertebral disc degeneration （IDD） in rats. MethodsIn the cell experiment， male rats were administrated with normal saline or low-， medium-， and high-dose （3.38， 6.75，13.5 g·kg^-1， respectively） Shentong Zhuyutang by gavage， respectively， and serum samples were collected after 7 days of continuous administration. Another 10 male rats were selected for the isolation of nucleus pulposus cells. The cell model of IDD was established by treatment with interleukin （IL）-1β. The modeled cells were then treated with Shentong Zhuyutang-containing serum and the ferroptosis inhibitor ferrostatin-1 （Fer-1）， respectively， to investigate the effects of Shentong Zhuyutang-containing serum on the proliferation and ferroptosis of nucleus pulposus cells. To study the role of silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2） in the regulation of ferroptosis in nucleus pulposus cells by Shentong Zhuyutang-containing serum， this study treated the cells with the SIRT1 inhibitor Ex 527 and the Nrf2 inhibitor ML385， respectively， in addition to the treatment with IL-1β and high-dose Shentong Zhuyutang-containing serum. The cell-counting kit-8 （CCK-8） assay and EdU staining were employed to measure the cell viability and proliferation， respectively. The Fe²⁺， glutathione （GSH）， and malondiadehyde （MDA） levels were measured by colorimetric assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family 4 （ACSL4）， Collagen Ⅱ， Aggrecan， SIRT1， and Nrf2. Immunofluorescence was used detect SIRT1 expression. In the animal experiment， male rats were treated with anulus puncture for the modeling of IDD. Rats were randomly assigned into sham operation， model， Shentong Zhuyutang-containing serum （13.5 g·kg^-1）， and positive control （nimesulide dispersible tablets， 0.18 mg·kg^-1） groups. Rats in the drug intervention groups were administrated with corresponding agents at 1 mL·kg^-1， and those in the sham operation and model groups were administrated with equal volumes of normal saline， once daily for 28 consecutive days. At the end of the last administration， the histopathological changes in the intervertebral discs of rats were observed by hematoxylin-eosin staining and scored by the Masuda method. Western blot was employed to determine the protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ in the nucleus pulposus tissue. ResultsCompared with the control group， the IL-1β group of nucleus pulposus cells showed elevated levels of Fe²⁺， MDA， and ACSL4 （P<0.05）， decreased cell viability， lowered GSH level， and down-regulated protein levels of GPX4， Collagen Ⅱ， and Aggrecan （P<0.05）. Shentong Zhuyutang-containing serum and Fer-1 reversed the effects of IL-1β on the viability and ferroptosis of nucleus pulposus cells and up-regulated the protein levels of Collagen Ⅱ and Aggrecan in nucleus pulposus cells （P<0.05）. Compared with the control group， the IL-1β group showcased down-regulated expression of Sirt1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the IL-1β group， the high-dose Shentong Zhuyutang-containing serum+IL-1β group showed up-regulated expression of SIRT1 and Nrf2 in nucleus pulposus cells （P<0.05）. Compared with the high-dose Shentong Zhuyutang-containing serum+IL-1β group， the ML385 group showed down-regulated protein levels of Nrf2 and GPX4， lowered GSH level， and elevated Fe²⁺ and MDA levels （P<0.05）. In addition， the Ex 527 group showed down-regulated protein levels of SIRT1， Nrf2， and GPX4 （P<0.05）. The results of the animal experiment showed that compared with the sham operation group， the model group had severe degeneration of the intervertebral disc tissue with increased pathological score， up-regulated protein level of ACSL4 （P<0.05）， and down-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. Compared with the model group， the Shentong Zhuyutang group showed alleviated IDD with declined pathological score， down-regulated protein level of ACSL4 （P<0.05）， and up-regulated protein levels of SIRT1， Nrf2， GPX4， and Collagen Ⅱ （P<0.05）. ConclusionShentong Zhuyutang may activate the SIRT1/Nrf2 signaling pathway to inhibit the ferroptosis of nucleus pulposus cells， thereby delaying the process of IDD in rats.

Objective:To explore the clinical manifestations and characteristics of serum adrenal cortex hormone spectrum in patients with adrenocortical hypercortisolism with different pathological types of adrenal adenoma.Methods:A retrospective analysis was conducted on 68 patients with adrenal Cushing's syndrome who underwent surgical treatment in the Department of Endocrinology and/or Urology, Peking University First Hospital from January 2018 to June 2022. Among them, 12 patients had obvious eosinophilic changes in pathology(eosinophilic group), and 56 patients had no obvious eosinophilic changes(non-eosinophilic group). Among eosinophilic group, one male and 11 females, age(49.83±9.87) years old, body mass index (BMI)(25.86±3.21) kg/m 2, systolic blood pressure (140.25±20.72)mmHg(1 mmHg=0.133 kPa), diastolic blood pressure(91.00±14.87)mmHg, 7 cases were overt Cushing's syndrome. Among non-eosinophilic group, 14 males and 32 females, age(52.91±10.82) years old, BMI (26.06 ± 3.57) kg/m 2; ystolic blood pressure (142.13±16.71) mmHg, diastolic blood pressure (83.63±11.41) mmHg; 16 cases of overt Cushing's syndrome. There was no statistically significant difference in the above indicators between the two groups ( P>0.05).In terms of laboratory tests, 0: 00 cortisol levels in the eosinophilic group and non-eosinophilic groups were 14.95(5.93, 23.2) ng/dl and 6.69(4.07, 11.35) ng/dl ( P=0.044), the cortisol levels after 1mg dexamethasone inhibition test were 20.19(11.29, 26.92) ng/dl and 5.94(2.68, 12.90) ng/dl ( P=0.005), and 8: 00, 16: 00, and 0: 00, ACTH levels were 2.08 (1.02, 2.90) pg/ml and 8.37(2.30, 11.67) pg/ml ( P=0.006), 1.22(1.00, 3.20) pg/ml, and 4.22(1.80, 6.33) pg/ml ( P=0.012), 0.65 (0, 2.63) pg/ml, and 2.76(1.44, 5.57) pg/ml( P=0.023), serum triglyceride were 1.92(1.31, 2.50) mmol/L and 1.31(1.04, 1.80) mmol/L ( P=0.026), and the differences were statistically significant. In terms of target organ damage, there were 6 cases and 10 cases ( P=0.017) in the eosinophilic group and non eosinophilic group with ventricular wall hypertrophy, 1 case and 0 cases( P=0.030) in the aortic dissection group, and 4 cases and 5 cases ( P=0.024) with four or more types of target organ damage, respectively, with statistically significant differences. Two groups of preoperative serum adrenal cortex hormone profiles were detected by liquid chromatography tandem mass spectrometry. The differences in adrenal cortex hormone profiles and hormone ratios between the two groups were compared. Age, gender, and statistically significant indicators were included in a multivariate logistic regression model to analyze the correlation between each indicator and eosinophilic changes. Results:Adrenal cortical hormone profile of the two groups showed that the serum estrone levels in the eosinophilic group and non-eosinophilic group were 20.27(13.49, 39.81) pg/ml and 12.59(8.08, 21.18) pg/ml ( P=0.034), and 11-hydroxyandrostenedione levels were 692.34(536.19, 1 049.66) pg/ml and 1 157.60(710.78, 1 539.30) pg/ml( P=0.026), with statistically significant differences; There were no statistically significant difference in the expression levels of other hormones ( P>0.05). In terms of hormone ratio, the estradiol/testosterone ratios in the eosinophilic and non eosinophilic groups were 0.14(0.08, 0.62) and 0.04(0.01, 0.09)( P=0.008), the estrone/androstenedione ratios were 0.06(0.05, 0.12) and 0.04(0.03, 0.06)( P=0.007), the 11-hydroxyandrostenedione/androstenedione ratios were 2.26(1.30, 2.69) and 4.03(2.48, 5.25)( P=0.008), the estriol/estrone ratios were 0.10(0.03, 0.29) and 0.25(0.12, 0.51)( P=0.016), the estriol/estradiol were 0.22(0.03, 0.30) and 0.33(0.12, 0.73)( P=0.032), and the differences were statistically significant. The results of multivariate analysis showed that estrone ( OR=1.04, 95% CI 1.01-1.07, P=0.009) and estrone/androstenedione ( OR=25 008 670.29, 95% CI 8.45-74 015 852 572 024.10, P=0.025) were independently associated with eosinophilic pathology. Conclusions:Adrenocortical hypercortisolism patients with eosinophilic pathology have higher levels of serum cortisol secretion, more pronounced inhibition of the hypothalamic pituitary adrenal axis, more significant metabolic disorders and target organ damage, and higher production of estrone.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Power supply plays a key role in ensuring animal robots to obtain effective stimulation. To extending the stimulating time, there is a need to apply photovoltaic cells and monitor their parameter variations, which can help operators to obtain the optimal stimulation strategy. In this paper, an online monitoring system of photovoltaic cells for animal robot stimulators was presented. It was composed of battery information sampling circuit, multi-channel neural signal generator, power module and human-computer interaction interface. When the signal generator was working, remote navigation control of animal robot could be achieved, and the battery voltage, current, temperature and electricity information was collected through the battery information sampling circuit and displayed on the human-computer interaction system in real time. If there was any abnormal status, alarm would be activated. The battery parameters were obtained by charging and discharging test. The battery life under different light intensity and the stimulation effect of neural signal generator were tested. Results showed that the sampling errors of battery voltage, current and electric quantity were less than 15 mV, 5 mA and 6 mAh, respectively. Compared with the system without photovoltaic cells, the battery life was extended by 148% at the light intensity of 78 320 lx, solving the battery life problem to some extent. When animal robot was stimulated with this system, left and right turns could be controlled to complete with the success rate more than 80%. It will help researchers to optimize animal robot control strategies through the parameters obtained in this system.
Animals ; Humans ; Robotics ; Electric Power Supplies ; Electricity ; User-Computer Interface

Objective:To investigate the effect of programmed death receptor (PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer.Methods:Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected. At the same time, all of the above-mentioned hepatitis B virus (HBV) patients were treated with nucleos(t)ide analogues. Patients clinical diagnostic data, laboratory test results, tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety, therapeutic anti-tumor effect, HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy, high viral load treatment condition, and HBV reactivation safety issues. Statistical analysis was performed by non-parametric rank sum test.Results:Therapeutic anti-tumor effect and safety profile were good in patients. The complete remission rate was reached 27.6%. Adverse reactions were mostly mild, and the incidence of serious adverse reactions was low. After 12 weeks of follow-up, HBV DNA and hepatitis B surface antigen (HBsAg) was quantitatively decreased ( P < 0.05). HBV DNA and HBsAg were decreased more significantly in patients with progressive disease (PD), stable disease (SD) and partial response (PR) ( P < 0.05). Five patients with HBV DNA ≥ 10 4 IU/ml had responded well to the tumor treatment without serious adverse reactions. One patient had a slight increase in HBV DNA and alanine aminotransferase, while there was no HBV reactivation and correlated liver damage. Conclusion:Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile. PD-1 treatment has a certain effect on HBV. Compared with non-responders, patients with tumor response have better antiviral treatment efficacy. The safety of treatment in patients with high viral load is manageable, and there are no safety issues related to HBV reactivation.

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Curriculum integration has become the core content of the current medical education reform.With the rapid development of information technology,how to reflect the teaching and learning effects and to further improve them,is one of the difficulties in the reform of the integrated curriculum.In view of the problems of single form of assessment model,separate classroom teaching and extracurricular teaching evaluation,low utilization of network and electronic teaching resources,we make full use of network methods to carry out reform on the current formative teaching evaluation system.With the purpose of formative assessment and evaluation,the "Blackboard network teaching system" of the curriculum has been built,and the evaluation indexes of classroom teaching and extracurricular teaching have been established.And at the same time,the formative assessment index has been enriched and perfected in a diversified form,and the formative assessment model adapted to the integrated curriculum is preliminarily explored.

Objective To analyze the typical imaging features of various internal biliary fistulas by multislice spiral CT (MSCT),and the diagnostic value.Methods the data of 56 cases of internal biliary fistula in Wuxi No.2 Affiliated Hospital of Nanjing Medical University from January 2011 to March 2018 were analyzed retrospectively.All cases were examined by MSCT plain scan and enhanced examination.The imaging features of various biliary fistula were analyzed and studied.Results Among 56 cases of biliary fistula,39 cases were gallbladder duodenum fistula,and the diagnostic sensitivity was 87.2％ (34/39).The total coincidence rate was 85.7％ (48/56).21 cases were fistula formation,and 11 cases of narrow neck syndrome.Gallbladder bile duct fistula,liver-gallbladder fistula,bile duct and duodenal fistula of 6 cases were showed.In 4 cases of complex gallbladder fistulas,3 cases showed fistula clearly including 2 cases of fistula and a "clover" sign.In the indirect CT signs of 56 cases of internal biliary fistula,the common imaging features:atrophy of gallbladder or incarceration,stone incarceration of biliary tract,gallbladder or choledochal duct and cavity viscera.Conclusion MSCT scan can not only distinguish the type of biliary fistula and the structure of fistula,but also display the fistula,shape,atrophy of gallbladder,gallbladder and bile duct gas,stone and surrounding conditions,which have important guiding significance for the formulation of the operation scheme.

Objective To investigate the imaging features of computed tomography (CT) examination of subacute gallbladder perforation.Methods The retrospective cross-sectional study was conducted.The clinical data of 24 patients with subacute gallbladder perforation who were admitted to the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University between January 2013 and January 2018 were collected.Patients underwent abdominal plain scan and enhanced scan in the arterial phase and portal venous phase of CT,and received percutaneous cholecystostomy,cholecystectomy,choledocholithotomy,T-tube drainage according to their conditions.Observation indicators and evaluation criteria:(1) CT examination situations."Barrier lake sign" is defined as presence of obvious or occult crevasse in the discontinuous gallbladder wall,with interrupt line seen in the portal venous phase and without crevasse enhancement.There is patchy effusion circled by annular wall around crevasse of gallbladder,shape like barrier lake,appearing as oval,semicircle,circular sector,triangle,etc.Annular wall consists of abscess wall,liver margin or both of them.With smooth inner wall of the abscess and irregular outer wall,abscess wall may be complicated with inflammatory exudation and strip shadow,showing intense enhancement in the venous phase.(2) Treatment and follow-up situations.Follow-up using outpatient examination and telephone interview to detect complications after discharge up to January 2018.Measurement data with skewed distribution were represented as M (range).Results (1) CT examination situations.① Completion status and primary diseases:of 24 patients,2 underwent abdominal plain scan,22 underwent abdominal plain scan combined with enhanced scan in the arterial phase and portal venous phase.The primary disease of all the 24 patients was biliary stone,including 18 located in gallbladder cavity,4 located at gallbladder neck and 2 combined with gallbladder stones and common bile duct stones.The maximum diameter was 2.0 cm (range,0.3-2.5 cm)in the 24 patients.② Crevasse of subacute gallbladder perforation:perforations were detected at the bottom of gallbladder in 11 patients,at body of gallbladder in 7 patients (1 with multiple perforations),at gallbladder neck in 1 patient,at bottom and body of gallbladder in 2 patients,and perforation spot was unable to judge in 3 patients.The maximum diameter of occult crevasses was ＜0.2 cm in 2 patients and maximum diameter of crevasses was 0.5 cm (range,0.2-1.0 cm) in other 22 with defined perforation spot.③ Imaging manifestations of "barrier lake sign":24 patients had manifestation of "barrier lake sign".Annular wall consisted of abscess wall,liver margin or both of them was found in 15,3,6 patients respectively.Gallbladder was partially or totally wrapped by abscess in 21 and 3 patients respectively.④ Gallbladder situation:of 24 patients,23 and 1 had gall bladder volume increased significantly and decreased slightly,with a maximum diameter of 10.0 cm (range,6.0-13.0 cm) and thickness of hydropic gallbladder wall as 0.5 cm (range,0.3-1.3 cm).⑤ Other effusion signs:24 patients had increased fat interval density around gallbladder,partly showing cord-like and line-like changes.(2) Treatment and follow-up situations:of 24 patients,10 underwent laparoscopic cholecystectomy,6 underwent open cholecystectomy,4 underwent cholecystectomy + choledocholithotomy + T-tube drainage,1 was converted to open cholecystectomy + choledocholithotomy + T-tube drainage after laparoscopic exploration,3 underwent cholecystectomy at 2 months after percutaneous cholecystostomy combined with anti-inflammatory treatment.Of 24 patients,22 were followed up for 6-31 months with a median time of 11 months.During the follow-up,2 patients were detected residual stones at fossa for gallbladder and end of the common bile duct,2 were detected cholangitis with stones,1 died of tumor,and other 17 survived well without recurrence of calculus or other complications.Conclusion The "barrier lake sign" is a typical feature of CT examination of subacute gallbladder perforation,which provides timely and accurately differential diagnosis and clinical treatment.

Objective To investigate whether MT1-MMP is involved in the inhibition effect of curcumin on the proliferation and invasion of breast cancer cell and the mechanism . Methods Firstly, MCF-7 cell lines transfected by MT1-MMP eukaryotic expression vector was established. We divided all cells into 3 groups,including null vector transfection group, non-transfected and transfected group with different concentrations of curcumin. The expression of MT1-MMP protein, the proliferation and invasion ability were respectively analyzed by western blot, transwell method, and cell counting kit-8 (CCK-8). Results The expression of MT1-MMP was inhibited by curcumin. Transwell and CCK-8 experiment indicated the proliferation and invasion abilities of MT1-MMP transfected MCF-7 cells were inhibited by curcumin in a concentration dependent manner. Conclusion The inhibition value of curcumin on proliferation and invasion is probably due to its ability to inhibit the expression of MT1-MMP.