Objective To explore the effect of low-dose cyclophosphamide(CTX)on apoptosis of implanted human lung carcinoma in nude mice.Methods BALB/c nude mice bearing lung carcinoma were randomized into several groups,each receiving different dose of CTX respectively.We investigated antitumor effect and toxicity of CTX.At the end of experiment,tumors were resected for immunohistochemical staining.Nuclear factor ?B(NF-?B P65)was detected and apoptosis was measured by TUNEL.Morphological changes of tumor cells were observed.Results The volume of tumors was much smaller in mice receiving continuous low-dose CTX than that receiving maximally tolerated dose of CTX and normal saline(control group).The apoptotic index was increased and NF-?B P65 decreased in the mice receiving low-dose of CTX.Conclusion The continuous low-dose of CTX inhibits the growth of implanted tumor and increases tumor cell apoptosis,which may be due to the down-regulation of nuclear factor ?B.

Objective To evaluate the expression of alpha-methylacyl-coenzyme-A racemase (AMACR,P504s) with immunohistochemical staining in diagnosis of prostate carcinoma. Methods A total of 133 specimens were taken from the patients (mean age,71 years),including 46 cases of prostate carcinoma (PCa) (1 case of stage A,19 cases of stage B,14 cases of stage C,12 cases of stage D;4 cases of gradeⅠ,14 cases of gradeⅡ,28 cases of grade Ⅲ),53 cases of benign prostate hyperplasia (BPH),13 cases of prostate intraepithelial tumor (PIN),9 cases of normal prostate,6 cases of prostatitis,3 cases of metastatic prostate cancer.Two sections of each specimen were made,with 1 stained by hematoxylin and eosin,and the other stained immunohistochemically by a rabbit monoclonal antibody to AMACR (P504s).AMACR staining expression was characterized as negative (score,1), weak (positive) (2), moderate (3) or strong (4). Results In 46 cases of PCa,AMACR staining expression was negative in 2 cases,weak in 1,moderate in 25 and strong in 18,with a mean staining intensity of 3.28 [95% confidence interval (CI), 3.07-3.50]. In 53 cases of BPH, the staining expression was negative in 47 cases, weak in 6, with a mean intensity of 1.11 (95% CI, 1.02-1.20).In 13 cases of PIN, the staining expression was negative in 12, weak in 1, with a mean intensity of 1.08 (95% CI, 0.91-1.24).The score of PCa group was significantly different from those of the latter 2 groups (P

Objective To investigate the clinical features of patients with bronchiectasis of different types.Methods One hundred and twenty two patients with bronchiectasis at stable stage were recruited from January 2014 to July 2015.The patients were typed as cystic bronchiectasis (n =45) or non-cystic bronchiectasis (n =77) by high resolution CT (HRCT),expectoration bronchiectasis (n =80) or dry brochiectasis (n =42) by clinical symptoms,bacterial colonization (n =42) or non-bacterial colonization (n =80) by sputum culture.The modified British Medical Research Council (mMRC) dyspnea scale,Leicester Cough Questionnaire (LCQ),St George's Respiratory Questionnaire (SGRQ) and pulmonary function test were used to assess the clinical features,and the episodes of exacerbations and hospitalization,and mortality during 1-year follow-up were documented.Results mMRC dyspnea scale (1.90 ± 0.94 vs.2.90±1.09,t=-5.040),LCQ (16.20±4.60 vs.11.20±2.20,t=8.114),SGRQ (36.80±13.10 vs.52.06±22.10,t=-4.780),FEV1％ pred (68.45 ±26.50 vs.52.22 ±20.60,t=3.458),FVC％ pred (72.20 ±26.32 vs.63.10 ±21.42,t =2.058),FEV1/FVC (75.14 ±20.52 vs.58.12 ± 19.82,t =4.546),diffusing capacity of the lung for carbon monoxide (DLCO) (76.24 ± 28.40 vs.54.32 ± 21.20,t =4.400),episodes of exacerbations (Z =-8.272) and hospitalization during 1-year follow-up [6(14.29％) vs.29(36.25％),x2 =6.495] in patients with dry bronchiectasis were significantly better than those in patients with expectoration bronchiectasis (all P ＜ 0.05).mMRC dyspnea scale (3.20 ± 2.10vs.2.10±1.40,t=3.131),LCQ (10.12±2.63vs.16.22 ±3.22,t=11.365),SGRQ (54.80± 18.12 vs.34.06 ± 12.10,t =6.839) and FEV1％ pred (46.52 ± 22.55 vs.58.22 ± 24.62,t=-2.611),FVC％ pred (60.24± 18.22 vs.70.10±24.20,t =-2.547),FEV1/FVC (62.54± 19.02vs.73.12 ±18.42,t=-3.025),DLCO (62.24 ±22.40 vs.74.52 ±26.26,t=-2.627),episodes of exacerbations (Z =10.213) and hospitalizations during 1-year follow-up [21 (46.67 ％) vs.14 (18.18％),x2 =1 1.260] in patients with cystic bronchiectasis were significantly more severe than those in patients with non-cystic bronchiectasis (all P ＜ 0.05).mMRC dyspnea scale (2.38 ± 1.45 vs.1.92 ± 1.14,t =2.175),LCQ (12.82 ±2.12 vs.16.20 ±3.96,t =-6.140),SGRQ (54.22±21.50 vs.41.20 ± 14.60,t =3.521) and FEV1 ％ pred (54.20 ± 21.60 vs.66.45 ± 28.24,t =-2.668),FVC％ pred (63.10 ±24.32 vs.73.46 ±25.30,t =-2.177),FEV1/FVC (62.22 ±20.80 vs.72.14 ±24.36,t =-2.243),DLCO (58.52 ± 20.42 vs.69.22 ± 25.60,t =-2.344),episodes of exacerbation (Z =19.352) and hospitalization during 1-year follow-up [19 (45.24％) vs.16 (20.00％),x2 =8.575] in patients with bacterial colonization bronchiectasis were significantly more severe than those in patients with non-bacterial colonization bronchiectasis (all P ＜ 0.05).However,there was no significant difference in mortality during 1-year follow-up (all P ＞ 0.05) among patients with different types of bronchiectasis.Conclusion Patients with cystic,bacterial colonization and expectoration types of bronchiectasis seem to have more severe symptoms,more episodes of exacerbations and hospitalizations than those of non-cystic,non-bacteria colonization and dry types of bronchiectasis.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

WHO Guideline on Country Pharmaceutical Pricing Policies,published in 2020,outlines 10 commonly used pricing methods internationally.However,due to the unique composition of costs for traditional Chinese medicine(TCM),directly applying pricing methods designed for chemical and biological drugs may lead to discrepancies.Currently,in China,drug pricing primarily in-volves internal reference pricing,tender negotiation pricing,promoting the use of quality-assured generic and biosimilar drugs,and centralized procurement.It systematically analyzes various pricing methods and identifies their applicability and underlying reasons concerning the pricing of TCMwithin the medical insurance system.The method of value-based pricing and increasing price transparency has advantages for the pricing regulation of traditional Chinese medicine under medical insurance.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.