Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Q_max）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ²=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Q_max （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Q_max than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.

ObjectiveTo observe the effect of Wuwei Fuzheng Yijing decoction on sperm DNA integrity in male infertility patients. MethodOne hundred male infertility patients with sperm DNA damage （spleen and kidney Qi deficiency and blood stasis） that met the inclusion criteria were randomly divided into an observation group （Wuwei Fuzheng Yijing decoction） and a control group （L-carnitine oral solution）， with 50 cases in each group. After 12 weeks of treatment， the DNA fragmentation index （DFI） and traditional Chinese medicine （TCM） syndrome score， progressive sperm motility （PR）， sperm survival rate， and sperm concentration of the two groups before and after treatment were observed and compared. ResultThe total effective rate of the observation group was 89.80% （44/49） higher than 62.50% （30/48） of the control group （P<0.05）. Compared with the conditions before treatment， the DFI and TCM syndrome score of the two groups were reduced after treatment， while the PR， sperm survival rate， and sperm concentration were increased （P<0.05）， and the observation group was superior to the control group in terms of the above indexes （P<0.05）. ConclusionWuwei Fuzheng Yijing decoction obviously repairs sperm DNA of male infertility patients and improves sperm quality， with high safety.

The cardiovascular patch, served as artificial graft materials to replace heart or vascular tissue defect, is still playing a key role in cardiovascular surgeries. The defects of traditional cardiovascular patch materials may determine its unsatisfactory long-term effect or fatal complications after surgery. Recent studies on many new materials (such as tissue engineered materials, three-dimensional printed materials, etc) are being developed. Patch materials have been widely used in clinical procedures of cardiovascular surgeries such as angioplasty, cardiac atrioventricular wall or atrioventricular septum repair, and valve replacement. The clinical demand for better cardiovascular patch materials is still urgent. However, the cardiovascular patch materials need to adapt to normal coagulation mechanism and durability, promote short-term endothelialization after surgery, and inhibit long-term postoperative intimal hyperplasia, its research and development process is relatively complicated. Understanding the characteristics of various cardiovascular patch materials and their application in cardiovascular surgeries is important for the selection of new clinical surgical materials and the development of cardiovascular patch materials.
Cardiac Surgical Procedures/methods* ; Tissue Engineering ; Heart Ventricles ; Heart Atria ; Treatment Outcome

Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.

Objective: To understand the epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in recent 5 years, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures. Methods: The two stage sampling method was used to survey 3 junior middle school schools randomly selected from Shunyi District, Beijing, in November 2013, December 2015 and November 2017. The number of students surveyed each year was 1 520, 1 404 and 1 467 respectively. Results: A total of 4 500 questionnaires were distributed and 4 391 questionnaires were valid, with an effective rate of 97.6%. The current smoking rate and the attempting smoking rate in Shunyi District junior high school students increased substantially, the difference was statistically significant(χ2=9.15, 11.54, P<0.01). The exposure rate of second-hand smoke among junior high school students in Shunyi District is increasing year by year. The current smoking rate and the attempting smoking rate of second-hand smoke at home and in public places were higher than those of non-exposed ones. The differences in the current smoking rates of junior high school students (χ2=25.86, 37.61, P<0.01) and the attempting smoking rate (χ2=49.51, 63-86, P<0.01) were statistically significant. The influence of Shunyi District junior high school students through different tobacco information access channels on the current smoking rate of junior high school students increased year by year. Different tobacco information access channels have significant difference in the influence of the junior middle school students’ attempting smoking rate(P<0.05). Conclusion The overall tobacco use of junior high school students in Shunyi District of Beijing is increasing by year. The exposure of second-hand smoke is not optimistic, and the supervision of tobacco information acquisition channels is urgent to be strengthened.

On October 3rd, 2017, one male patient, aged 27 years, was admitted to our hospital 6 hours after hydrothermal scald of torso, buttocks, and limbs. The total area of burn was about 60% total body surface area, and the depth was from deep partial-thickness burn to full-thickness burn. Immediately after admission, the patient was given symptomatic support treatments, such as anti-shock, fluid replacement, and anti-infection, etc. After being treated by debridement and xenogenic (porcine) skin grafting for 2 times, the wounds were healed well. On the 12th day of admission, linezolid was used to prevent infection according to the results of microbial culture and drug sensitivity test, since when the level of his blood lactate continued to increase. After 8 days, linezolid was discontinued and vitamin B1 was given orally for 1 week, and the level of lactic acid gradually decreased to normal in result. This case was used mainly to analyze whether linezolid could directly cause hyperlacticemia and its important mechanism, aiming at reminding clinicians of being alert to the risk of hyperlacticemia when using linezolid. If hyperlacticemia occurs, linezolid should be discontinued immediately and vitamin B1 should be taken orally to correct the high lactic acid value, and the treatment plan should be adjusted if necessary.

The commercial gene test is a kind of detection service different from genetic diagnosis in medical institutions.There is no specific legislation on gene discrimination and genetic information security related to it.This paper adopted the method of comparative study to sort out the related legal issues of commercial gene test,and put forward the regulation ideas and scheme.

Objective:To investigate the influence of chemotherapy on the phenotype of secreted protein, acidic and rich in cysteine (SPARC) in gastric cancer (GC). Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC patients. Among these patients, 54 with preoperative chemotherapy and 78 without preoperative chemotherapy were selected to analyze the effect of chemotherapy on SPARC phenotype by comparing the postoperative specimens of the two cohorts. Results:SPARC expression was higher in GC lesions than in the desmoplastic stroma surrounding the tumor cells and noncancerous tissues. High SPARC expression was related to invasion depth, lymph node metastasis, and TNM staging. SPARC expression was lower in patients with preoperative chemotherapy than in controls ( P<0.05). Gross type, histology, depth of invasion, lymph node metastasis, TNM staging, and SPARC phenotype correlated with the overall survival of the patients with preoperative chemotherapy. Further multivariate analysis suggested that lymph node metastasis, histology, and SPARC phenotype after chemotherapy were independent prognostic indicators of GC. Conclusion:SPARC expression was associated with invasion depth, lymph node metastasis, TNM staging and GC prognosis. Preoperative chemotherapy may change the phenotype of SPARC in GC patients.

BACKGROUND: Pressure overload can lead to the activation of reninangiotensin-aldosterone system, and then left ventricular remodeling occurs.Captopril can reverse this progress.OBJECTIVE: To observe the effect of captopril in reversing left ventricular remodeling in rats with pressure overload and to elucidate its possible mechanism.DESIGN: A randomized controlled trial.SETTING: Department of Integrated Traditional Chinese Medicine and Western Medicine, Nanjing General Hospital () Nanjing Military Area Command of Chinese PLA; Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine; Postdoctor Institute of Hebei Medical University.MATERIALS: The experiment was conducted in the Laboratory of Shanghai University of Traditional Chinese Medicine between January 1998 and October 1998. Totally 153 male Wistar rats were recruited.There were 5 experiments, 36 rats in each experiment except 9 rats in the fourth one.METHODS: A total of 36 Wistar male rats selected for each experiment were randomly divided into sham operation group, model group and captopril group. Rats in model group received modeling for 4 weeks, then gastric perfusion with 15 mL/kg of distilled water once per day for 4 consecutive weeks. Abdominal aorta of the rats in sham-operation group were separated without closure by sliver clip, then 4 weeks later the procedure was the same as that in model group. In captopril group, 4 weeks after modeling, the rats were performed gastric perfusion with diluted captopril of 100 mg/kg, once a day for 4 consecutive weeks.MAIN OUTCOME MEASURES: The effect of captopril on left ventricular mass index (LVMI), mRNA expression of collagen type Ⅰ and Ⅲ, content of plasma angiotensin Ⅱ (Ang Ⅱ ) and left ventricular tissue Ang Ⅱ,plasma atrial natriuretic factor (ANF), and serum aldosterone (ALD) level.RESULTS: Totally 153 rats entered the result analysis. During the test for detecting the absorbance (A) of collagen type Ⅰ, 3 rats in sham operation group and 3 in captopril group died, and 1 rat died in model group; finally 29 rats were involved. During the test for detecting the absorbance (A) of collagen type Ⅲ, 3 rats died in sham operation group, 4 rats diedin model group, and 2 rats died in captopril group; finally 27 rats were involved. All in sham operation group and captopril group was lower than that in model group [(2.24±0.12)/1 000, (2.67±0.40)/1 000, (3.15±0.47)/1 000, t=2.649,cantly lower in sham operation group and captopril group than in model group [(0.57±0.19, 0.86±0.25, 2.79±2.00), t=3.661, 3.170, P ＜ 0.01, 0.05].operation group and captopril group than in model group [(0.48±0.10,sion of mRNA of collagen type Ⅰ: It was significantly lower in sham operation group and captopril group than in model group [(79.1 ±18.6)%,plasma Ang Ⅱ content: It was significantly lower in sham-operation group and captopril group than in model group [(130.2±30.2),(137.6±39.5),was significantly lower in sham operation group and captopril group than in model group [(170.6±51.6), (202.5±64.2), (339.3±115.4) μg/L, t=4.623,P ＜ 0.01].type Ⅲ and mRNA expression in rats with pressure overload, suggesting its captopril on left ventricular remodeling might be related to decreasing circulating or local Ang Ⅱ level, plasma ANF and serum aldosterone as well as affecting the expression of collagen type Ⅰ and type Ⅲ mRNA.