Current practices in the harmonisation of autoantibodies test / 中华内科杂志

Standardisation and harmonisation of the detection of autoantibodies is important for the clinical application of autoantibodies. However, achieving complete standardisation is difficult and involves several challenges due to the complexity and particularity of autoantibody detection. Harmonisation is feasible and valued, but it involves all aspects and processes of autoantibody detection. Based on the consensus and practice of the clinical application of autoantibody detection in recent years, we discuss harmonisation in this review.

Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China / 中华医学杂志(英文版)

BACKGROUND@#Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).@*METHODS@#A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.@*RESULTS@#A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8-29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.@*CONCLUSIONS@#Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis / 中华医学杂志(英文版)

BACKGROUND@#Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.@*METHODS@#Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.@*RESULTS@#Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks.@*CONCLUSION@#This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Systematic Review on Effects of Acupuncture Combined with Lifestyle Modification on Essential Hypertension / 中国中医药信息杂志

Objective To evaluate the effects of acupuncture combined with lifestyle modification for essential hypertension by Meta-analysis. Methods Clinical randomized controlled trial literature about acupuncture combined with lifestyle modification for essential hypertension in CNKI, WanFang Data, CBM, VIP, PubMed, Embase, and Web of Science since establishment to February 20, 2017 were retrieved. Data extraction and quality assessment of studies were conducted by two researchers independently, and the Meta-analysis was performed by the software of RevMan5.3. Results 5 articles involving 467 patients were included. The results of Meta-analysis showed that acupuncture combined with lifestyle modification had more significant effect than lifestyle modification alone in lowing SBP [SMD=-1.52(-2.40,-0.64)], in lowing DBP [SMD=-1.02(-2.01,-0.03)], total effective rates [RR=1.27(1.13, 1.43)]. Conclusion Compared with lifestyle modification alone, acupuncture combined with lifestyle modification have significant effects for patients with essential hypertension, but because of the fewer studies included, bigger heterogeneity between studies and the lower quality of included studies still exist, the results should be further verified, and clinical applications should be treated with caution.

Investigation of the cognition and behavior on drug safety in Beijing middle school students / 北京大学学报(医学版)

Objective:To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education.Methods:A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools.Multi-stage proportionate stratified cluster sampling was adopted to enroll participants.In addition to demographic questions,the questionnaire included 17 questions assessing the cognition and behavior of safe drug use,prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education.Descriptive statistical methods were applied using the SAS 9.2 software.Results:Of the 4 220 students investigated,2 097(49.7％) were males and 2 123(50.3％) were females.The average age was (14.3 ± 1.7) years.2 030(48.1％) students were from downtown areas,1 511(35.8％) were from urban-rural linking areas and 679(16.1％) were from rural areas.Half (51.5％) of the respondents were junior high school students,and the others were from senior high schools (34.2％) and vocational high schools (14.3％).Most of the students (89.6％) lived off campus.The awareness rate of drug safety knowledge was 74.4％,the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156,P ＜0.001).Both the awareness rates and the drug safety behavior scores were statistically different among the students in different regions,different school types and different residence types (P ＜ 0.001).Multiple factors analysis demonstrated the correlation between the cognition degrees of both drug safety knowledge,behavior and the above factors.Of all the students,80.4％ agreed that any drug could have adverse drug reactions;40.5％ were aware that antibiotics couldn't kill viruses;as many as 49.6％ mistook aspirin as antibiotic;97.4％ would read drug instructions before taking them;Only 42.4％ put expired drugs into special recycling bins;49.8％ would deviate from the suggested dosage and frequency of their medication when they were sick with common diseases.Conclusion:Overall,the cognition of drug safety in Beijing middle school students is good,but problems still exist in medication adherence,the management of expired drugs and the antibiotics cognition,which need to be fixed through specific,pointed way of education.And more efforts should be made to improve the cognition in rural regions,vocational high schools and on campus students.

Expression of IL-17 and Syndecan-1 in Nasal Polyps and Their Correlation with Nasal Polyps / 华中科技大学学报（医学）（英德文版）

Nasal polyp (NP) is a common chronic inflammatory disease of the nasal cavity and sinuses.Although some authors have suggested that NP is related to inflammatory factors such as interleukin (IL)-1β,IL-5,IL-8,granulocyte-macrophage colony-stimulating factor (GM-CSF),tumor necrosis factor (TNF)-α,and IL-17,the mechanisms underlying the pathogenesis and progression of NP remain obscure.This study investigated the expression and distribution of IL-17 and syndecan-1 in NP,and explored the roles of these two molecules in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) and non-Eos CRSwNP.Real-time PCR and immunohistochemistry were used to detect the expression of IL-17 and syndecan-1 in samples [NP,unciform process (UP) from patients with CRS,and middle turbinate (MT) from healthy controls undergoing pituitary tumor surgery].The results showed that the expression levels of IL-17 and syndecan-1 were upregulated in both NP and UP tissues,but both factors were higher in NP tissues than in UP tissues.There was no significant difference in IL-17 levels between the Eos CRSwNP and non-Eos CRSwNP samples,and syndecan-1 levels were increased in the non-Eos CRSwNP tissues as compared with those in Eos CRSwNP tissues.In all of the groups,there was a close correlation between the expression of IL-17 and syndecan-1 in nasal mucosa epithelial cells,glandular epithelial cells,and inflammatory cells,suggesting that IL-17 and syndecan-1 may play a role,and interact with each other,in the pathogenesis ofnon-Eos CRSwNP.

Analysis on the disinfection quality in nurseries and kindergartens in Changning District of Shanghai from 2010 to 2014 / 上海预防医学

Objective To investigate the disinfection quality and provide scientific basis for the prevention and control of infectious diseases in nurseries and kindergartens in Changning District of Shanghai. Methods On-site investigation and sampling examination were used during the continuous monitoring of the effect of disinfection in nurseries and kindergartens in Changning District of Shanghai. Results The eligible rates of disinfection quality during 2010-2014 in the nurseries and kindergartens of Changning District in Shanghai were 98.07%,98.93%,99.09%,97.11% and 98.10% successively. The eligible rates of indoor air, surfaces of environmental objects, hands of staff, eating utensils, disinfection solution in use were 99.74%,99.67%,93.24%,99.06% and 98.09% respectively. Conclusion The sanitary disinfection quality in nurseries and kindergartens of Changning in Shanghai is satisfactory as a whole, however,there is still weakness in the disinfection quality of the hands of staff, disinfection solution in use and eating utensils.

Efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We conducted a multi-centered open clinical study on 165 BPH patients treated with Saw Palmetto Extract Capsules at a dose of 160 mg qd for 12 weeks. At the baseline and after 6 and 12 weeks of medication, we compared the International Prostate Symptom Scores (IPSS), prostate volume, postvoid residual urine volume, urinary flow rate, quality of life scores (QOL), and adverse events between the two groups of patients.</p><p><b>RESULTS</b>Compared with the baseline, both IPSS and QOL were improved after 6 weeks of medication, and at 12 weeks, significant improvement was found in IPSS, QOL, urinary flow rate, and postvoid residual urine. Mild stomachache occurred in 1 case, which necessitated no treatment.</p><p><b>CONCLUSION</b>Saw Palmetto Extract Capsules were safe and effective for the treatment of BPH.</p>

Dynamic Wnt5a expression in murine hair follicle cycle and its inhibitory effects on follicular

OBJECTIVE@#To analyze the dynamic expression of Wnt family member 5A (Wingless-type MMTV integration Wnt site family, member 5a) in murine hair cycle and its inhibitory effects on follicle in vivo.@*METHODS@#Situ hybridization in full-thickness skin was used to observe the change of mouse protein expression in different growth stages, and Ad-Wnt5a was injected after defeathering to observe the hair follicle growth in vivo.@*RESULTS@#The Wnt5a mRNA was expressed at birth, and was firstly increased then decreased along with the progress of the hair cycle. It reached the peak in advanced stage of growth cycle (P<0.05). Rhoa and β-catenin expression levels were significantly decreased in three groups. Rac2 expression was significantly up-regulated, and the expression level of Wnt5a, Shh and Frizzled2 was increased, but less significantly than group 2.@*CONCLUSIONS@#The expression of Wnt5a mRNA is consistent with change of murine follicle cycle, and has obvious inhibitory effects on the growth of hair follicle in vivo, indicating that it is antagonistic to Wnts pathway and interferes the growth of follicle together.

Epidemiological and clinical features of occult hepatitis B in HIV infection without antiretroviral treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate and analyze the differential prevalence, as well as the risk factors and clinical features, of occult hepatitis B virus (HBV) infection in the human immunodeficiency virus (HIV)-infected population without antiretroviral therapy (ART) as compared to the general (non-HIV-infected) population.</p><p><b>METHODS</b>Two-hundred-and-forty-eight individuals with confirmed HIV infection but ART naive (males: 220, females: 28; 15-82 years old) were enrolled in the study, along with 121 healthy individuals (confirmed HIV antibody-negative; males: 53, females: 68; 20-88 years old). HBV markers (hepatitis B surface antigen (HBsAg); hepatitis B e antigen (HBeAg); anti-HBs, anti-HBe and anti-hepatitis B core (HBc) antibodies) were detected by microparticle enzyme-linked immunosorbent assay (AxSYM immunology analyzer manufactured by Abbott Laboratories); all cases and controls were confirmed negative for hepatitis B surface antigen (HBsAg). Then, the HBV DNA level in serum was detected using nucleic acid amplification assay (COBAS AmpliPrep/COBAS TaqMan HBV test, version 2.0 manufactured by Roche). CD4+ T lymphocytes were measured by flow cytometry, and alanine aminotransferase (ALT, marker of liver function) was measured by enzymatic assay.</p><p><b>RESULTS</b>Twenty-four of the HIV cases (9.7%) and four of the healthy controls (3.3%) tested positive for HBV DNA; the amount of individuals with HBV DNA-positivity was significantly higher in the HIV-infected group (P = 0.035). Among the 24 cases of HBV DNA(+) HIV-infected individuals, the lowest HBV DNA load was < 20 IU/ml and the highest was 3.22 x 10s IU/ml; nine of the individuals (37.5%) had HBV DNA load > 100 IU/ml, four (16.7%) had 20-99 IU/ ml, and 11 (45.8%) had < 20 IU/ml. Among the total HIV-infected cases with HBV DNA-positivity, 7.3% (8/110) were anti-HBc(+)/anti-HBs(+), 20.8% (11/53) were anti-HBc(+)/anti-HBs(-), 14.3% (3/21) were anti-HBc(-)/anti-HBs(+), and 3.1% (2/64) were anti-HBc(-)/anti-HBs(-). The amount of individuals with HBV DNA-positivity in the anti-HBc(+)/anti-HBs(-) group was significantly different from those in the anti-HBc(+)/anti-HBs(+) group (P = 0.018) and the anti-HBc(-)/anti-HBs(-) group (P = 0.003). However, multiple comparison of HBV DNA loads detected between the four groups of HBV marker status revealed no significant difference (P = 0.805). Furthermore, statistical analysis provided no evidence to support that occult hepatitis B infection in HIV-infected individuals had any impact on CD4+ T lymphocytes count (Z = 1.902, P = 0.059) or ALT levels (Z =1.401, P = 0.161).</p><p><b>CONCLUSION</b>HIV-infected individuals who are ART naive and HBsAg(-) have a higher incidence of HBV DNA-positivity than individuals in the general (non-HIV-infected) population. In addition, the highest rate of occult hepatitis B among the HIV-infected cases occurred among individuals who were anti-HBc(+)/anti-HBs(-).</p>

Sixty-two severe and critical patients with 2009 influenza A (H1N1) in Shanghai, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pandemic influenza A (H1N1) emerged rapidly in China in May 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A (H1N1) disproportionately affects younger ages and causes generally mild disease. To characterize disease progress, comorbidities, and treatment outcomes among consecutive severe and critically ill patients in a hospital served as a reference center for the care of patients with H1N1 in Shanghai, China.</p><p><b>METHODS</b>A retrospective study on 62 severe and critically ill patients with 2009 influenza A (H1N1) was conducted in Shanghai Public Health Clinical Center. Demographic data, symptoms, comorbidities, disease progression, treatments, and clinical outcomes were collected for analysis.</p><p><b>RESULTS</b>Sixty-two severe or critically ill patients were admitted to the hospital with confirmed 2009 influenza A (H1N1) infection. The median age of the study cohort was 40 years old with a range from 18 years to 75 years, and 67.7% were males. All patients presented with fever and respiratory symptoms. At presentation, 34 patients (54.8%) had comorbidities such as smoking (29.0%), hypertension (29.0%) and hepatitis B virus infection (9.7%). The median time from symptom onset to hospital admission was 6 days (interquartile-range 3 - 14 days) and 23 critically ill patients were admitted to Intensive Care Unit after admission. All the patients received neuraminidase inhibitors (oseltaminir), while 60 patients (96.7%) were treated with antibiotics, and 39 (62.9%) with corticosteroids. Twenty-three critical cases received noninvasive mechanical ventilation on the first day of admission, and 3 of them ultimately required invasive ventilation. Four death reports (6.5%) were filed within the first 14 days from the onset of critical illness with the primary causes of severe acute respiratory distress syndrome, hypoxemia, or complications, secondary infection and sepsis, pyopneumothorax and stroke.</p><p><b>CONCLUSIONS</b>Severe illness from 2009 influenza A (H1N1) infection in Shanghai occurred among young individuals. Critical cases were associated with severe hypoxemia, multisystem organ failure, and a requirement for mechanical ventilation. Most patients had a good prognosis.</p>

Retroperitoneal laparoscopic radical nephrectomy in the treatment of renal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of retroperitoneal laparoscopic radical nephrectomy in the treatment of renal cancer.</p><p><b>METHODS</b>The clinical data of 53 cases who underwent retroperitoneal laparoscopic radical nephrectomy were analyzed retrospectively.</p><p><b>RESULTS</b>Fifty-two cases achieved successful retroperitoneal laparoscopic radical nephrectomy, a conversion to open surgery was required in one case because of severe adhesion. The operation time was 75 min to 220 min (mean, 125 min), the blood loss was 50 ml to 420 ml (mean, 120 ml), and the postoperative hospital stay was 6 d to 12 d. Complications occurred in 4 cases. Pathological examination showed that 47 cases were of renal clear cell carcinoma, 5 of chromophobe carcinoma, and 1 of cystic renal cell carcinoma. Follow-up for 1 month to 5 years showed no tumor recurrence and metastasis.</p><p><b>CONCLUSION</b>Retroperitoneal laparoscopic radical nephrectomy is a safe and effective treatment for patients with stage T1 - 2N0M0 renal cell carcinoma.</p>

Peg-interferon alfa-2a and highly active antiretroviral drug therapy on hepatitis C patients with AIDS / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect and side-effect of peg-interferon alfa-2a (PEG-IFN alfa-2a) and highly active antiretroviral therapy (HAART) for patients infected with hepatitis C virus (HCV) and co-infected with human immunodeficiency virus (HIV).</p><p><b>METHODS</b>Twenty-two patients with HCV/HIV co-infection received highly active antiretroviral therapy initially; after their CD4 lymphocyte counts rose to over 0.20x10(9)/L, they were separated into two groups: one group with CD4 lymphocytes over 0.35x10(9)/L (high group) and one group with CD4 lymphocytes below 0.35x10(9)/L (low group). Both groups were given 180 microg of PEG-IFN alfa-2a every week intramuscularly. HCV RNA and HIV RNA loads, blood cell and CD4 lymphocyte counts, and liver functions were routinely examined.</p><p><b>RESULTS</b>After 12, 24 and 48 weeks of PEG-IFN alfa-2a therapy, mean HCV RNA loads reduced 2.0650 log10 copies/ml (t=3.8733), 2.9146 log10 copies/ml (t=7.6741) and 2.4315 log10 copies/ml (t=5.8202) from the baseline at week 0 in the 13 patients in the high group, and reduced 1.1522 log10 copies/ml (t = 2.8937), 1.4189 log10 copies/ml (t=2.4422) and 1.1167 log10 (t=1.1261) in the 8 patients of the low group. However, there was no significant difference between the early viral response rate (EVR) and the end of treatment viral response rate (ETVR) of the two groups. In the high group, the white blood cell count was lower at 24 weeks than the base line (t=2.4700), and the blood platelet count was lower both at 24 and 48 weeks than the base line (t=2.3273 and t=3.6149).</p><p><b>CONCLUSIONS</b>PEG-IFN alfa-2a can effectively reduce HCV RNA loads in patients with HCV-/HIV co-infection, and the inhibition rate in patients with higher CD4 lymphocyte counts is better. The EVR and ETVR of the two groups of patients show similar results after the treatment. PEG-IFN alfa-2a can reduce the white blood cell counts and the blood platelet counts in the peripheral blood.</p>

Construction of small interfering RNA targeting heparanase gene and its inhibitory effect on the in-vasiveness of human malignant melanoma cell line A375 in vitro / 中华皮肤科杂志

Objective To construct the small interfering RNA (siRNA) targeting heparanase gene and its expressing vector,and to observe its interference effect on the expression of heparanase gene and inhibitory effect on the invasive potential of human malignant melanoma A375 cells.Methods Three siRNAs were designed.The recombinant plasmid pRNATU6.1/heparanase-siRNA was designed and constructed. A375 cells were cultured,and transfected with pRNATU6.1/heparanase-siRNA.The cells treated with lipo- fectamine or Opti-MEM served as the controls.Real-time fluorescence quantitative PCR and Western blot were performed to evaluate the expression of heparanase RNA and protein in these treated A375 cells.The in vitro invasive potential of treated A375 cells was assessed by Matrigel gel assay.Results The siRNA targeting heparanase gene was successfully cloned to the eukaryotic expressing vector pRNATU6.1.The expression levels of both heparanase RNA and protein decreased significantly in siRNA-transfected A375 cells than those in the control cells.The in vitro invasive potential of siRNA-transfected cells was also signifi- cantly inhibited as compared with that of the control cells (P