Study on the correlation between early three-dimensional gait analysis and clinical efficacy after robot-assisted total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy.@*METHODS@#Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation.@*RESULTS@#There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024).@*CONCLUSION@#The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.

Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats / 中西医结合学报

OBJECTIVE@#Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats.@*METHODS@#HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations.@*RESULTS@#In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).@*CONCLUSION@#This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

Pulmonary deportation of hydatidiform mole: a 12-year, single tertiary center experience in China / 中华医学杂志(英文版)

BACKGROUND@#Pulmonary deportation of hydatidiform mole is an exceedingly rare entity. The underlying mechanisms and proper management strategies remain unclear based on sporadic case reports over the past six decades. This study aimed to investigate the clinical features and rational treatment of patients with benign molar pregnancies with pulmonary deportation based on our experience.@*METHODS@#Medical records of 20 cases of hydatidiform mole with pulmonary deportation were retrospectively reviewed at Peking Union Medical College Hospital from November 2006 to May 2019. The detailed information of all patients was recorded and analyzed. Patients were divided into different groups according to their characteristics and Mann-Whitney U test was used to compare the duration to achieve a normal β-human chorionic gonadotrophin (β-hCG) level after the first evacuation among groups.@*RESULTS@#Initial pulmonary computed tomography scans showed suspected bilateral, left and right chest deportation of hydatidiform mole in 12, four, and four patients, respectively, with the maximum nodular diameter ranging from 0.6 to 1.2 cm. Ten patients achieved lesion resolution while the remaining ten patients achieved decreases in the size of their pulmonary lesions. The median duration to achieve a normal β-hCG level after the first evacuation was 15.5 (13.0, 21.9) weeks. There was no significant difference in the duration to achieve a normal β-hCG level after the first evacuation between two groups based on age (≥40 years vs. 0.5 cm vs. ≤0.5 cm: 13.0 [11.3, 17.2] weeks vs. 16.0 [14.5, 23.8] weeks, Z = 1.815, P = 0.070), and number of uterine evacuations (once vs. twice or three times: 15.0 [13.0, 16.3] weeks vs. 16.0 [12.8, 23.9] weeks, Z = 0.832, P = 0.405). The post-molar cohort was followed up for 17 to 139 months, and no gestational trophoblastic neoplasia was observed.@*CONCLUSIONS@#No surgeries other than uterine evacuation and no chemotherapy regimens are recommended for such patients if they achieve satisfactory decreases in the level of hCG and gradual decrease or disappearance of pulmonary deportation nodules. Patients should be informed about the necessity of long-term follow-up. More collaborative international studies on this exceedingly rare condition may guide decisions regarding optimal management strategies.

Effect and Mechanism of Modified Banxia Xiexintang on Depression During Perimenopause / 中国实验方剂学杂志

Objective::To observe the effect of modified Banxia Xiexintang on depression during perimenopause, in order to study itseffecton 5-hydroxytryptamine (5-HT) and proinflammatory factors. Method::One hundred and thirty-nine patients were randomly divided into control group (69 cases) and observation group (70 cases) by random number table.Patients in control group got tibolone tablets, 2.5 mg/time, 1 time/day, and paroxetine hydrochloride tablets, 20 mg/time, 1 time/day.In addition to the therapy in control group, patients in observation group were added with modified Banxia Xiexintang, 1 dose/day.The course of treatment was 8 weeks.And before and after treatment, Hamilton depression scale for-17 items (HAMD-17), Zung's self-rating depression scale (SDS), hamilton anxiety scale (HAMA), improvement Kupperman(KI), liver depression and spleen deficiency syndrome, menopause-specific quality of life questionnaire (MENQOL) and treatment emergent symptom scale (TESS) were scored, and levels of 5-HT, rain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected. Result::After treatment, scores of HAMD-17 and SDS in observation group were lower than those in control group (P<0.01). And the effect on trea depression in observation group was better than that in control group (Z=2.074, P<0.05). The degree of depression in observation group was ligher than that in control group (Z=2.157, P<0.05). And scores of HAMA, KI and liver depression and spleen deficiency syndrome were lower than those in control group (P<0.01). The severity of perimenopausal syndrome was ligher than that in control group (Z=2.046, P<0.05). And scores of vasomotor symptoms and psychological symptoms of MENQOL scale and the total scores were lower than those in control group (P<0.05). Levels of 5-HT and BDNF were higher than those in control group (P<0.01), while levels of IL-1β, TNF-α and TESS were lower than those in control group (P<0.01). Conclusion::In addition to theroutine western medicine, modified Banxia Xiexintang can alleviate the severity of depression, release the symptoms of depression, anxiety and perimenopausal syudrome(PMS), improve the quality of life, inhibit pro-inflammatory factors, and enhance the expressions of 5-HT and BDNF, with no adverse event.

Comparison of postoperative cognitive function in patients undergoing general anesthesia using sevofurane alone, sevofurane plus propofol and sevoflurane plus dexmedetomidine / 第二军医大学学报

Objective: To compare the postoperative cognitive function of patients undergoing general anesthesia using three strategies: sevoflurane alone, sevoflurane plus propofol, and sevoflurane plus dexmedetomidine. Methods: Ninety patients aged 18 to 65 years who were scheduled to undergo laparoscopic hysteromyomectomy were selected for this study. The American Society of Anesthesiologists (ASA) was classified as Grade I or Grade II. Ninety patients were divided into three groups by random number table: sevoflurane group, sevoflurane-propofol group and sevoflurane-dexmedetomidine group, with 30 patients in each group. The induction drugs of anesthesia were the same in the three groups. Sevoflurane group was maintained with 1-1.2 minimum alveolar concentration (MAC) sevoflurane; sevoflurane-propofol group was maintained with 0.5 MAC sevoflurane and target controlled infusion propofol (target blood concentration was 2-3 μg/mL); and sevoflurane-dexmedetomidine group was maintained with 0.5 MAC sevoflurane, intravenous pump loading dose of dexmedetomidine was 1 μg/kg (pump infusion for 10 min), and dexmedetomidine was continuously pumped at a dose of 0.2 μg/(kg · h) until 30 min before the end of the operation. Cognitive function was measured 1 d before operation and 7 d after operation, and plasma levels of inflammatory factors were measured before operation and 24 h after operation. Results: There were no significant differences in age, body mass index, preoperative score of mini-mental state examination scale, operation time or blood loss among the three groups (all P>0.05). The Hopkins visual learning test (HVLT1) and forward digit span test (FSDT) scores 7 d after operation (23.22 ± 4.75, 2.39 ± 0.69) were significantly higher in the sevoflurane-dexmedetomidine group than those in the sevoflurane group (21.00 ± 4.96, 2.17 ± 0.39), but lower than those in the sevoflurane-propofol group (24.89 ± 6.20, 2.84 ± 0.96), and the differences were statistically significant (all P<0.05). The plasma interleukin 6 (IL-6) level ([19.93 ± 10.04] pg/mL) in the sevoflurane-dexmedetomidine group was significantly lower than those in the sevoflurane group ([36.06 ± 17.03] pg/mL, P<0.05) and sevoflurane-propofol group ([39.99 ± 19.39] pg/mL, P<0.05). Conclusion: Compared with sevoflurane alone and sevoflurane plus propofol, patients with sevoflurane plus dexmedetomidine for general anesthesia have better postoperative cognitive function, which may be related to the low level of IL-6 after surgery.

Effect of micro-fracture and comminution of fat pad on meniscal tear healing under arthroscopy / 中国内镜杂志

Objective To analyze the curative effect of fossa intercondyloidea of micro-fracture and comminution of subcutaneous fat pad on meniscal tear healing under arthroscopy. Methods During the clinical operation, the samples of the micro-fracture and fat pad comminution were attracted to the outside of the joint. The source and properties of cells were identified based on preclinical medicine experiment in vitro. In clinical research, 75 cases of the simple meniscus injury were selected from January 2014 to January 2016 and divided into three groups refer to treatment: Group A, B and C. Different treatments were used in the three groups. Group A - micro-fracture group; Group B - fat pad group; Group C - blank group. All patients' conditions were assessed with Lysholm, VAS score and adverse event (Swelling, anterior knee pain). Results In the preclinical medicine experiment, cells released by micro fracture were fibroblast-like cells which tend to grow more rapidly in vortex shape. Cells released by comminution of fat pad contained a small amount of impurities and necrotic cells and are mostly similar to fibroblast in long spindle shape. Besides, the Human MSC Analysis Kit was used to authenticate two cells which were considered to be as BMSCs and IPFPSCs. In clinical research, all patients received an average of 10 (8 ～ 11) months follow-up visit. No severe complication, such as blood-vessel and nerve injury, infection occurred after operations in the patients followed. Before receiving the treatment, difference in Lysholm, VAS score and general condition of joint of Group A and B, C showed no statistical difference (P > 0.05). Compared with those before operation and after operation in both of four groups, the Lysholm and VAS score were improved (P < 0.05). Besides, there had significantly difference between group A and C, B and C after post treatment in Lysholm and VAS score (P < 0.05), however, group A and B did not. Compared group A and C, the early prevalence of adverse event of group B was higher, but last follow-up show no difference between three groups. Conclusion Combined with basic experimental and clinical studies, our research suggest that micro-fracture and comminution of fat pad have good effect on the repair of meniscus injuries. Nevertheless, it should be concerned that early prevalence of increased swelling amd anterior knee pain of comminution of fat pad.

Role of YAP in the proliferation of lung cancer A549 cells induced by lipopolysaccharide / 医学研究生学报

Objective Chronicinflammation is closely related to the occurrence and development of tumor , but the specific mechanism is still unknown .The aim of this study was to investigate the effect of lipopolysaccharide ( LPS) on the proliferation of lung adenocarcinoma A 549 cells and the role YAP in the process . Methods CCK-8 was used to detect the proliferation of A 549 cells stimulated by different concentrations of LPS .Western-blot ( WB) and immunofluorescence were used to detect the expression and local-ization of YAP protein, respectively.Inhibition rate of target protein and mRNA was measured by WB and RT-PCR respectively after inhibiting the expression of YAP by siRNA .After inhibiting the expression of YAP , the cell proliferation of A 549 stimulated with LPS was detected by CCK-8 again. Results After treatment with LPS for 72 h, the A values increased significantly (P<0.05) after treat-ment with 0.01, 0.1, and 1μg/mL compared with those treated with 0μg/mL LPS.The cell proliferation ability remained the strongest af-ter treatment with 0.1 μg/mL LPS.Western blot analysis showed that compared with 0μg/mL, all the LPS treated A549 cells could up-reg-ulate the expression of YAP protein ( P<0.05) at 48 h.Andthe 0.1μg/mL LPS was the most obvious .The results of RT-PCR showed that the expression of YAP mRNA in YAP siRNA1 group, YAP siRNA2 group and YAP siRNA3 group was significantly lower than that in blank group (P<0.05).Compared with NC siRNA group, the ex-pression of YAP mRNA in YAP siRNA1 group,YAP siRNA2 group and YAP siRNA3 group was significantly decreased (P<0.05).The result of Western blot was consistent with that of RT-PCR.YAP siRNA could significantly inhibit the expression of YAP protein in A549 cells.And the inhibition rate of YAP siRNA1 was the highest (P<0.05).Compared with the control group, A549 cells were sig-nificantly proliferated in LPS group at 24, 48 and 72 h (1.17±0.08 vs 1.47±0.08, 1.95±0.16 vs 2.35±0.07, 2.46±0.07 vs 3.01±0.08, P<0.05).Compared with LPS group, the proliferation of A549 cells in YAP siRNA+LPS group at 48 and 72 h (1.92±0.15, 2.38± 0.07) was significantly decreased (P<0.05). Conclusion Our work suggested that low concentration of LPS promoted the prolifera-tion of A549 cells by enhancing the expression of YAP , and these results would provide a new theoretical basis for the mechanism of LPS-induced proliferation of lung cancer cell .

Effect of adenovirus delivered tissue inhibitor of metalloproteinases 3 on the irradiation sensitivity of human papillomavirus positive cervical cancer cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of adenovirus-delivered tissue inhibitor of metalloprotein- ases-3 (Ad-TIMP-3) on the irradiation sensitivity of human papillomavirus (HPV)-positive cervical cancer cells.</p><p><b>METHODS</b>An adenovirus expressing TIMP-3 (Ad-TIMP-3), alone or in combination with irradiation,was used to treat HPV-positive cervical cancer cells HeLa-Luc and CaSki. The effects of Ad-TIMP-3 on the proliferation of HeLa-Luc and CaSki cells were detected with MTT assay. The effect of the combination of Ad-TIMP-3 and X-ray on the proliferation of cells were determined by clone formation assay. Twenty nude mice were equally randomly divided into four groups: normal control group,Ad-TIMP-3 group,X-ray group,and combination group. The size of tumor was measured separately,and tumor growth curves were drawn.</p><p><b>RESULTS</b>Ad-TIMP-3 significantly inhibited the proliferation of HPV-positive cervical cancer cells in a dose-dependent manner. Combination of Ad-TIMP-3 and X-ray significantly decreased the clones of HeLa-Luc and CaSki than Ad-TIMP-3 or X-ray alone (P<0.05). The tumor weights were (0.216±0.098), (0.276±0.073), and (0.044±0.043) g, respectively, in Ad-TIMP-3 group, X-ray group,and combination group, which were all significantly lower than that in normal control group [(0.534±0.218) g] (all P<0.05). In addition,the tumor weight in the combination group was significantly lower than that in Ad-TIMP-3 group and X-ray group (both P<0.05). The tumor inhibition rate was 59.60%, 48.30%, and 91.80% in X-ray group, Ad-TIMP-3 group and combination group, respectively.</p><p><b>CONCLUSIONS</b>Ad-TIMP-3 can effectively inhibit the proliferation of cervical cancer cells. When combined with X-ray,it can remarkably increase the irradiation sensitivity of HPV-positive cervical cancer cells,and thus suppress the tumorigenesis capability of these cells in vivo.</p>

Resources of Lycium species and related research progress / 中国中药杂志

Solanaceae Lycium speices are deciduous shrubs. In ancient Chinese medicine works, Lycium plants are described to work well in nourshing liver and kidney, enhancing eyesight, enriching blood, invigorating sex, reducing rheumatism and so on. More of their functions such as immunity improvement, anti-oxydation, anti-aging, anti-cancer, growth stumulation, hemopoiesis enhancing, incretion regulating, blood sugar reducing, bearing improvement and many other new functions are conformed in modern clinic researches. Lycium is also widely used in brewing, beverage and many other products. The world Lycium-related researches are mostly on Lycium species genesis and evolution, sexual evolution, active ingredient separation and pharmacological effects. The future research direction is indicated in this article, molecular evolution and systematics rather than traditional taxonomy will do better in explanation of present global distribution of Lycium species; comparative genomics research on Lycium will be a whole new way to deep gene resources exploration; relationship of genetic diversity and active ingredient variation on L. barbarum and L. chinense will lay theory basis for new germplasm development, breeding, cultivation and production regionalization.

Effects of acupuncture and embedding thread on central monoamine neurotransmitters in the depression model rat / 中国针灸

<p><b>OBJECTIVE</b>To compare therapeutic effects of acupuncture and embedding thread on depression and to probe the mechanism.</p><p><b>METHODS</b>Thirty-two adult SD rats, 16 females and 16 males, were randomly divided into a normal group, a model group, an acupuncture group and an embedding thread group, 8 rats in each group. Separated feeding, long-term unpredictable and middle stimulation stress were used for development of depression rat model. At the same time, the treatment groups were treated for 21 days. The changes of norepinephrine (NE), 5-hydoxytryptamine (5-HT) and dopamine (DA) contents in the brain were detected by high performance liquid chromatography-electrochemical detector.</p><p><b>RESULTS</b>Compared with the normal group, 5-HT, NE and DA contents in the hypothalamus and hippocampus decreased significantly in the model group (P < 0.05, P < 0.01); compared with the model group, the contents of the central monoamine neurotransmitters increased in both the acupuncture group and the embedding thread group, but the embedding thread group had more obvious action in improvement of 5-HT and DA levels in the hypothalamus and DA level in the hippocampus than the acupuncture group with no significant difference between the two groups.</p><p><b>CONCLUSION</b>Both acupuncture and embedding thread therapy are effective for the depression model rat. They play the therapeutic role through regulating central monoamine neurotransmitters.</p>

Apoptosis of multiple myeloma RPMI8226 cell line induced by matrine / 中国实验血液学杂志

This study was aimed to investigate the effect of matrine on multiple myeloma RPMI8226 cell line and its mechanism. The RPMI8226 cells were treated with various concentrations of matrine for 24 and 48 hours; the promoting-apoptosis effect of matrine on RPMI8226 cells was observed by morphology, Annexin-V analysis, DNA agarose gel electrophoresis, mitochondrial transmembrane potential detection, etc. The results indicated that after treatment of RPMI8226 cells with matrine, the typical morphology of cell apoptosis appeared, Annexin-V analysis showed positive, the typical ladder was observed in DNA agarose gel electrophoresis, and the mitochondrial transmembrane potential decreased. It is concluded that the matrine can effectively inhibite the RPM8226 cell growth and reduce cell viability in dose-and time-dependent manner. It is presumed that the matrine induces RPMI8226 cell apoptosis through mitochondrial signaling pathway.

Application of bone marrow biopsy imprint in evaluating cellularity / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the value of bone marrow biopsy imprint in evaluating cellularity.</p><p><b>METHODS</b>The bone marrow tissues were obtained by trephine biopsy from 272 patients, and then put on the slides to make the imprints. The imprints was stained by Wright-Giemsa method, and the bone marrow smears and imprints were examined simultaneously according to the bone marrow cellularity criteria.</p><p><b>RESULT</b>In bone marrow cellularity, four grades (distinct decrease, extreme decrease, distinct increase, and extreme increase) were significantly higher in bone marrow imprints than those in bone marrow smears (P <0.05), but there was no significantly differences between bone marrow imprints and sections (P >0.05). Using bone marrow sections as standard, in cellularily decreasing samples, the consistent rate of bone marrow imprints and smears were both high (84.4% and 97.9%), in the group of the normal and increased cellularity, the consistent rate of the bone marrow imprints (84.4% and 97.7%) was significantly higher than that in smears (60% and 64%, P<0.01). The sensitivity, specificity, Youden index, positive predictive value and positive likelihood rate of bone marrow imprints were all higher than those of the smears. Using the bone marrow sections as gold standard, in 124 cases with decreased cellularity in smears, the positive diagnosis rate for aplastic anemia and dyshaematopoiesis based on bone marrow imprints was 37.1% with a false positive rate of 7.3% which was lower than that of the bone marrow smears (false positive rate of 29.8%, P<0.01).</p><p><b>CONCLUSION</b>To evaluate bone marrow cellularity, bone marrow imprint is better than bone marrow smear. The combination of the two examinations can make the diagnosis more convenient and quicker.</p>

Fertility preservation in the management of gynecologic cancers / 中国医学科学院学报

Cancer treatment has improved the rate of survival associated with neoplasias, and cancer survivors are more and more interested in preserving fertility potential. This article focuses on new and innovative techniques as well as approaches to treat gynecologic cancers while minimizing the negative fertility effects of cancer treatment. In particular, the radical trachelectomy procedure in cervical cancer, hormonal treatment of early endometrial cancer, conservative surgical management of early-stage epithelial ovarian cancer, and novel assisted reproductive technologies for women with impaired ovarian function after cancer treatment are discussed.

Outcome of gestational trophoblastic neoplasia patients with residual lung tumor after completion of treatment / 中华妇产科杂志

0.05)between the recurrent rate[2.2%(10/463)]of the CR patients with lung metastasis and the progression rate of the 152 patients.Conclusions After normalization of ?-hCG titer,patients whose lung tumors remained unchanged even after several additional courses of chemotherapy should be considered as CR patients.Follow-ups should be strictly carried out on these patients,especially at around 6 months after the completion of treatment,and particularly for high-risk and drug-resistant choriocarcinoma patients.