Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Investigation of the current situation of nipple-sparing mastectomy: a large multicenter study in China (CSBrs-003) / 中华医学杂志(英文版)

BACKGROUND@#Mastectomy techniques have been extended to nipple-sparing mastectomy (NSM). This study aimed to assess the actual application of NSM in China and identify the factors influencing postoperative complications.@*METHODS@#The clinical data of 615 patients (641 surgeries) undergoing NSM from January 1st, 2018 to December 31st, 2018 at 28 centers nationwide were retrospectively analyzed to obtain the rate of NSM and investigate factors related to NSM surgery.@*RESULTS@#The proportion of NSM surgery performed in this study was 2.67% (17/641). Malignant breast tumors accounted for the majority of NSM surgery (559/641, 87.2%). A total of 475 (77.3%) patients underwent NSM combined with reconstructive surgery. The rate of reconstruction decreased with age in our study, and implants were the most common option (344/641, 53.7%) in reconstruction. Radial incision was the most selected method regardless of reconstruction. However, for those who underwent reconstruction surgery, 18.4% (85/462) of cases also chose curvilinear incision, while in the simple NSM surgery group, more patients chose circumareolar incision (26/136, 19.1%). The tumor-to-nipple distance (TND) influenced postoperative complications (P = 0.004). There were no relationships between postoperative complications and tumor size, tumor location, histologic grade, molecular subtype, nipple discharge, and axillary lymph nodes.@*CONCLUSIONS@#NSM surgery is feasible and only TND influenced postoperative complications of NSM surgery. But the proportion of NSM surgery performed is still low in nationwide centers of China. The selection criteria for appropriate surgical methods are important for NSM in clinical practice. To optimize clinical applications of NSM, further multicenter prospective randomized controlled studies are needed.@*TRIAL REGISTRATION@#ChiCTR.org.cn, ChiCTR1900027423; http://www.chictr.org.cn/showprojen.aspx?proj=38739.

Effects of oxygen-enriched negative pressure wound therapy in improving wound microenvironment to tissue proliferation and vascularization / 医学研究生学报

ObjectiveIt is indefinited that oxygen-enriched negative pressure wound therapy, namely negative pressure wound therapy combined with topical oxygen therapy (NPWT+TOT), improve the effects of wound microenvironment in tissue proliferation and vascularization. The objective is to discuss effects of oxygen-enriched negative pressure wound therapy in improving wound microenvironment to tissue proliferation and vascularization.MethodsTo select sixty-four patients in the outpatient wound care center of the eastern theater general hospital from January to October, 2019, which were randomly divided into the experimental group (NPWT+TOT) and the control group (NPWT), 32 cases in each group. The patients were treated with oxygen-enriched negative pressure wound and negative pressure wound respectively for 2 weeks to observe the changes of wound temperature and PH before and during intervention. Bacterial culture and immunohistochemical staining which were made from wound secreta and wound bed tissues to observe bacterial culture results, tissue proliferation activity and microvascular density before intervention and 14 days after intervention. After the intervention, the patients were treated by standard wet therapy and followed up to wound healing or 3 months after the intervention to observe the wound healing rate and wound healing time.ResultsAfter two weeks' continuous intervention, wound temperature of patients increased and PH value decreased significantly between the experimental group and the control group. Meanwhile, the intervention group was more effective, and there were significant differences between the two groups (P<0.05). The positive rate of bacterial culture after intervention in the experimental group and the control group was 26.67% and 41.38% respectively, with no statistically significant difference (P=0.233). Compared with the control group, the increase of tissue activity and microvascular density in the experimental group was more significant (P<0.05). After three months' follow-up, the wound healing rate of the experimental group was increased by 12.5% compared with the control group, and the average wound healing time was shortened by 9.2 days.ConclusionOxygen-enriched negative pressure wound therapy can improve wound microenvironment, reduce the positive rate of wound bacterial culture, improve the proliferation activity of wound tissue and degree of vascularization, and promote wound healing.

Comparison of the effectabout improved negative pressure wound therapy with filling dressing for treating traumatic wounds / 医学研究生学报

Objective The purpose of this study is to use nano-silver dressing as filling dressing for negative pressure wound therapy, and to observe the effect of treating traumatic infected wounds, so as to provide a basis for optimizing negative pressure wound therapy technology. Methods Eighty patients with physical traumatic wounds were enrolled in the outpatient wound care center. They were randomly divided into the intervention group and the control group (n=40 in each group). In the intervention group, the filling dressing for negative pressure wound therapy used nano silver dressing. In the control group, the standard negative pressure wound therapy with normal saline gauze as filling dressing was adopted. All patients were treated with negative pressure for at least 14 days, and then were treated with moist wound therapy until followed up for wound healed. The wound volume reduction rate was the main outcome indicator 14 days after intervention in the two groups. The bacterial positive rate and the wound healing rate at the end of 3 months follow-up, and final healing time were the secondary outcome indicators. Results 36 cases in the control group and 40 cases in the intervention group completed the expected negative pressure wound therapy time and follow-up. The baseline data of the two groups had no difference. The wound volume reduction rate (70.95±20.73)% in the intervention group after 14 days of treatment was significantly higher than that in the control group (64.42±22.33)% (P< 0.05), and the bacterial positive rate (20%) was lower than that in the control group (44.44%)(P< 0.05). At the end of the follow-up, the healing rate of the intervention group (97.50%) was higher than that of the control group (66.67%)(P<0.001). The healing time of the intervention group（50.85±15.81d）was shorter than of the intervention group (62.58±16.18d)(P<0.05). Conclusion Improving the filling dressing for negative pressure wound therapy can effectively reduce the volume of traumatic wound and the positive rate of pathogenic bacteria, and help to control wound infection and improve wound healing outcomes.

Surgical exposures of the distal humeral fractures: An anatomical study of the anterior, posterior, medial and lateral approaches / 中华创伤杂志(英文版)

PURPOSE@#Exposure of the articular surface is the key to the successful treatment of intra-articular fractures of distal humerus. Anterior, posterior olecranon osteotomy as well as medial and lateral approaches are the four main approaches to the elbow. The aim of this study was to compare the exposure of distal articular surfaces of these surgical approaches.@*METHODS@#Twelve cadavers were used in this study. Each approach was performed on six elbows according to previously published procedures. After completion of each approach, the exposed articular surfaces were marked by inserting 0.5 mm K-wires along the margins. The elbow was then disarticulated and the exposed articular surfaces were painted. The distal humeral articular surfaces were then closely wrapped using a piece of fibre-glass screen net with meshes. The exposed articular surfaces and the total articular surfaces were calculated by counting the number of meshes, respectively.@*RESULTS@#The average percentages of the exposed articular surfaces for the anterior, posterior olecranon osteotomy, medial and lateral approaches were 45.7% ± 2.0%, 53.9% ± 7.1%, 20.6% ± 4.9% and 28.5% ± 6.3%, respectively.@*CONCLUSION@#The anterior and posterior approaches provide greater exposures of distal humeral articular surface than the medial and lateral ones in the treatment of distal humeral fractures.

Correlation between expression of 1 α -hydroxylase and hypocalcaemia in rats with severe pancreatitis

OBJECTIVE@#To investigate the essential biochemical indices like 1 -hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.@*METHODS@#A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.@*RESULTS@#Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3, 6, 12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3, 6, 12 hours after the operation (P<0.05). It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h, 12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976, P<0.001; r=0.948, P<0.001; r=0.742, P=0.001) and also positive correlation between the 1-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h, 3 h, 6 h and 12 h (r=0.935, P<0.001; r=0.952, P<0.001; r=0.917, P<0.001; r=0.874, P<0.001).@*CONCLUSIONS@#At the early stage of the kidney injury, the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.

Correlation between expression of 1 α -hydroxylase and hypocalcaemia in rats with severe pancreatitis

Objective: To investigate the essential biochemical indices like 1 -hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them. Methods: A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope. Results: Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3, 6, 12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3, 6, 12 hours after the operation (P<0.05). It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h, 12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976, P<0.001; r=0.948, P<0.001; r=0.742, P=0.001) and also positive correlation between the 1-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h, 3 h, 6 h and 12 h (r=0.935, P<0.001; r=0.952, P<0.001; r=0.917, P<0.001; r=0.874, P<0.001). Conclusions: At the early stage of the kidney injury, the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.

Effect of dihydroartemisinin combined irradiation on the apoptosis of human lung cancer GLC-82 cells and its mechanism study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of dihydroartemisinin (DHA) combined irradiation on the apoptosis of human lung cancer GLC-82 cells and to study its mechanism.</p><p><b>METHODS</b>The growth inhibition rate of GLC-82 cells acted by different concentrations DHA was detected using MTT assay at 24, 48, and 72 h, respectively. Clone forming test was used. With multi-target single-hit model, the radiosensitization effect was assessed by calculating sensitizing enhancement ratio (SER).The effect of DHA combined irradiation on the apoptosis of GLC-82 cell cycle distribution and apoptosis were measured by flow cytometry. The protein expression of p53, p21, Bcl-2, and Bax were detected by Western blot.</p><p><b>RESULTS</b>Different concentrations DHA (4, 8, 16, 32, 64, and 128 μg/mL) had cytotoxicity on GLC-82 cells. The IC50 for 24, 48, and 72 h was 38.25,20.58, and 10.36 μg/mL, respectively, in obvious dose- and time-dependent manner. The growth inhibition rate was more significantly increased than that of the blank control group (P < 0.01, P<0.05). DHA had sensitization enhancement effect on GLC-82 cells, with SER of 1.4. DHA combined irradiation could obviously change the structure of GLC-82 cells cell cycle and induce apoptosis (with the apoptosis rate of 21.5%), which was significantly different from that of the blank control group (P < 0.05). Western blot showed the expression of p53 and p21 protein could be increased by DHA combined irradiation, and the expression of Bcl-2 protein down-regulated (P <0.01, P <0. 05).</p><p><b>CONCLUSIONS</b>DHA had stronger cytotoxicity and radiosensitization on GLC-82 cells. Its mechanisms might lie in making the arrest of GLC-82 cells' growth at G0/G1 phase, decreasing the ratio of cells at S phase, restoring the function of p53, decreasing the expression of Bcl-2 protein, and inducing apoptosis in GLC-82 cells.</p>

TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Primary neuroendocrine tumor of the testis: clinicopathological study of 7 cases / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and treatment of primary neuroendocrine tumor (NET) of the testis.</p><p><b>METHODS</b>Using light microscopy and immunohistochemistry, we studied 7 cases of primary NET of the testis, reviewed relevant literature, and analyzed the clinical manifestations, histomorphologic and immunohistochemical characteristics, treatment and prognosis of the tumor.</p><p><b>RESULTS</b>The 7 male patients, at the mean age of 40.6 years, all presented with testicular painless masses, none accompanied with carcinoid syndrome. Histologically, the uniform tumor cells were arranged in trabecular, island, solid and/or flake structures and locally in a tubulo glandular pattern, round and polygonal in shape, with a small amount of lipid vacuoles in the eosinophilic cytoplasm. The cells had round nuclei with fine chromatin and rarely identified mitosis. Immunohistochemical staining showed that the tumor cells were positive for Syn, CgA, NSE and CK, with a Ki-67 positive rate of < 2%.</p><p><b>CONCLUSION</b>Primary NET of the testis is a rare and low-grade malignancy. Early diagnosis and surgical resection are essential for good prognosis. Immunohistochemistry helps its diagnosis and differential diagnosis from other metastatic neuroendocrine carcinoma, teratomas with carcinoid, seminoma, and Sertoli cell tumor.</p>

TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without recieiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

The effect of drainage in cavities on preventing from grade B and C of the pancreatic fistula after pancreaticoduodenectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the effect of drainage in cavities on preventing from grade B and C of the pancreatic fistula after pancreaticoduodenectomy (PD).</p><p><b>METHODS</b>From June 2008 to June 2010, the medical team had performed the operations of digestive tract reconstruction by the same way in 68 cases with PD. There were 43 male and 25 female patients, with a mean age of (64 ± 3) years. The patients were simply randomly divided into drainage in cavities group (DC, n = 32) and conventional drainage group (CD, n = 36) according to the different drainage way. The methods of drainage in cavities were composed of three aspects which include drainage in main pancreatic duct, drainage around cholecystojejunostomy anastomosis and peripancreatic drainage. The clinical parameters of the two groups were collected. The characteristics of the drainage juice which include color, volume and amylase value in the two groups were compared. The incidence and severity grading of pancreatic fistula between the two groups were evaluated.</p><p><b>RESULTS</b>The average of amylase value and the peripancreatic drainage flow were (1401 ± 8) U/L and (49 ± 5) ml in the DC group. Their average in the CD group were (2160 ± 13) U/L and (76 ± 4) ml. There was significant statistical difference in the peripancreatic drainage flow between the two groups (t = 2.597, P = 0.031). The amylase values of the drainage juice between the two groups were of no statistical difference (P > 0.05). According to the definition of pancreatic fistula by an international study group, the incidence of pancreatic fistula in the DC group was 25.0% (8/32) and the CD group 30.5% (11/36) (P > 0.05). The proportion of grades B and C of pancreatic fistula in the DC group had statistical difference compared with one of the CD group (χ(2) = 4.797, P = 0.029).</p><p><b>CONCLUSION</b>Drainage in cavities could significantly decrease and the occurring ratio of grade B and C of pancreatic fistula after PD.</p>

Comprehensive measures for improving the radical resection rate and safety of Bismuth-Corlette type III hilar cholangiocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the comprehensive measures for improving radical resection rate and safety of Bismuth-Corlette type III hilar cholangiocarcinoma.</p><p><b>METHODS</b>The clinical data of 15 patients with Bismuth-Corlette type III hilar cholangiocarcinoma who performed radical resection from June 2009 to December 2011 was analyzed retrospectively. There were 11 male and 4 female patients, aged from 45 to 74 years (mean 59 years). The preoperative evaluation were conducted by using magnetic resonance cholangiopancreatography (MRCP), dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System providing three-dimensional reconstruction of tumor, bile duct, hepatic artery and portal vein, which could help to chose the appropriate treatment modality. All patients were treated with selective hemi-hepatic vascular control of removal liver, hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy. The merits of each evaluation methods and measures of surgical treatment were analyzed thoroughly.</p><p><b>RESULTS</b>The preoperative evaluation modalities including the dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could clearly show the involvement of bile duct, hepatic artery and portal vein invaded by the tumor. The satisfactory postoperative recovery could be achieved by the remnant liver volume of > 40% after the hemi-hepatectomy combined with whole caudate lobe resection through the selective preoperative biliary drainage and hemihepatic vascular control. The mean complication was transient aggravated liver dysfunction. There was no death reported during perioperative period in the group.</p><p><b>CONCLUSIONS</b>The preoperative imaging evaluation modalities including MRCP, dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could do favor for the preoperative evaluation of invasion degree of hilar cholangiocarcinoma and the selection of appropriate surgical treatment. Hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy could be an alternative management of Bismuth-Corlette type III hilar cholangiocarcinoma.</p>

Immunohistochemistry using epidermal growth factor receptor mutation-specific antibodies of delE746-A750 and L858R in lung adenocarcinomas / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the immunohistochemical detection of epidermal growth factor receptor(EGFR) mutations using two EGFR mutation-specific monoclonal antibodies: delE746-A750 and L858R.</p><p><b>METHODS</b>A total of 175 paraffin-embedded lung adenocarcinoma tissue samples previously genotyped by directive DNA sequencing were subject to immunostaining using delE746-A750 and L858R antibodies.</p><p><b>RESULTS</b>There was no significant difference of mutation detection between DNA sequence analysis and delE746-A750 and/or L858R immunostaining (33.7% vs 30.9%, P > 0.05). The overall sensitivity, specificity, positive predictive value and negative predictive value of immunostaining using these two EGFR mutation-specific antibodies were 83.1%, 95.7%, 90.7% and 90.9%, respectively.</p><p><b>CONCLUSION</b>With high sensitivity and good specificity, immunohistochemistry using EGFR mutation-specific monoclonal antibodies is an adequate, easy and cost-effective prescreening method to detect EGFR mutations using paraffin-embedded tissue specimens of lung adenocarcinomas.</p>

Prognostic value of T lymphocytes infiltration in breast cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.</p><p><b>METHODS</b>Paraffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) .</p><p><b>RESULTS</b>Intraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.</p><p><b>CONCLUSIONS</b>In the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.</p>

Relevance of molecular alterations in histopathologic subtyping of lung adenocarcinoma based on 2011 International Multidisciplinary Lung Adenocarcinoma Classification / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the relevance of molecular alterations and histopathological subtypes of lung adenocarcinoma according to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification.</p><p><b>METHODS</b>Mutations of epidermal growth factor receptor (EGFR) 18-21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung adenocarcinoma which underwent complete tumor resection, were detected by immunohistochemistry, PCR-amplifying and gene sequencing. The relevance of the molecular alterations to histopathological subtypes based on the new classification and 2004 WHO classification were further characterized.</p><p><b>RESULTS</b>Mutations of EGFR were observed in 49.6% of lung adenocarcinomas, involving mainly E21 (52.4%, 55/105) and E19 (36.2%, 38/105). Mutations of KRAS were detected in 8% cases of adenocarcinoma, involving mainly codon 12 (15/17). EML4-ALK fusions were found in 6.1% of lung adenocarcinoma, the most common fusion mutation was type V1 (E13; A20) (7/13), followed by type V3a/b (E6a/b; A20) (4/13). Based on the new classification, 7/10 lepidic, 63.2% (48/76) papillary, and 5/8 micropapillary predominant adenocarcinomas harbored EGFR mutations. EGFR mutations showed significant difference among different histological subtypes (P = 0.008). KRAS mutations were most frequently found in invasive mucinous adenocarcinoma (1/2), followed by colloid predominant adenocarcinoma (3/7). There was significant difference of KRAS mutations among different histological subtypes (P = 0.003). EML4-ALK fusions were most frequently found in the solid predominant with mucin production subtype (15.4%, 6/39), followed by colloid predominant adenocarcinoma (1/7), and no significant difference of EML4-ALK fusions was found among different histological subtypes (P = 0.181). Significant TTF-1 overexpression was observed in adenocarcinomas harbored EGFR mutations (P = 0.008), and no or significantly lower level expression of TTF-1 was observed in adenocarcinomas harbored KRAS mutations (P = 0.000). However, there was no association between TTF-1 expression and EML4-ALK fusions (P = 0.274). Based on the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P = 0.000), rather than EGFR (P = 0.502), showed significant differences among different subtypes. According to both classification systems, the difference of "triple negative" adenocarcinomas was not significant among different subtypes (P = 0.684, P = 0.449, respectively).</p><p><b>CONCLUSIONS</b>The new classification, combined with TTF-1 immunomarker, can help to predict the molecular alterations of EGFR and KRAS genes, but can not indicate the EML4-ALK fusion in lung adenocarcinoma. Lepidic, papillary, and micropapillary predominant adenocarcinomas with TTF-1 expression are closely related to the presence of EGFR mutation, and invasive mucinous adenocarcinoma, while colloid predominant adenocarcinoma without TTF-1 expression is closely related to the presence of KRAS mutation.</p>

Pharmacokinetics of photosensitizer m-THPC in rat models of liver cancer via orthotropic implantation using Walker-256 / 中华外科杂志

<p><b>OBJECTIVE</b>To study the pharmacokinetics, distribution and excretion of m-THPC in rat models of liver cancer via orthotropic implantation using Walker-256.</p><p><b>METHODS</b>After an intravenous injection of m-THPC with 0.3 mg/kg, the concentrations of m-THPC in biological specimens were determined by a fluorescence method. The data obtained were processed with PK-GRAPH pharmacokinetic procedure.</p><p><b>RESULTS</b>The disposition of m-THPC in rat models of liver cancer Walker-256 was conformed to a two compartment model with T(1/2)α = 1.18 h, T(1/2)β = 22.57 h at the dose of 0.3 mg/kg.m-THPC was shown to be widely distributed to the various tissues. There was a highest drug accumulation in liver and liver cancer, and lowest in skin and muscle. Ratio of m-THPC concentration in the Walker-256 tumor compared to normal tissue reach the peak 24 h after m-THPC administration.</p><p><b>CONCLUSIONS</b>m-THPC is distributed widely and eliminated at a rapid rate in Walker-256 rats. Twenty four hours after m-THPC administration may be the best time for photodynamic therapy of liver cancer.</p>

Expression and clinical significance of kidney injury molecule-1 in renal epithelial neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression and clinical significance of kidney injury molecule-1 (KIM-1) in primary and metastatic renal epithelial neoplasms.</p><p><b>METHODS</b>A total of 136 cases of kidney neoplasms were retrospectively reviewed including 63 primary clear cell renal cell carcinomas (RCCs), 22 papillary RCCs, 13 chromophobe RCCs, 7 oncocytomas, 7 RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 24 metastatic clear cell RCCs. Immunostaining for KIM-1 and kidney-specific-protein (Ksp)-cadherin were performed and the relationship to tumor stage and grade in clear cell RCCs was investigated.</p><p><b>RESULTS</b>Expression of KIM-1 was detected in 77.8% (49/63) of clear cell RCCs, 90.9% (20/22) of papillary RCCs, 1/13 of chromophobe RCCs, 7/7 of RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 87.5%(21/24) of the metastatic RCCs, but not detected in 7 cases of oncocytomas. A diffuse expression of KIM-1 was more frequently observed in Furhman nuclear grade III/IV clear cell RCCs (P = 0.010). Ksp-cadherin expression was mainly observed in chromophobe RCCs and oncocytomas.</p><p><b>CONCLUSIONS</b>KIM-1 is a specific biomarker for injuried kidney proximal tubules and the corresponding neoplasms, and has a high specificity and sensitivity for primary or metastatic clear cell RCCs, papillary RCCs and RCCs associated with Xp11.2 translocation/TFE3 gene fusions. Combination of KIM-1 and Ksp-cadherin immunostaining can lead to a more precise histological classification of primary kidney epithelial neoplasms and improve the diagnostic accuracy of metastatic RCCs.</p>

Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.</p><p><b>METHODS</b>Nude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.</p><p><b>CONCLUSIONS</b>Treatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.</p>

Study on the relations between high risk human papillomavirus and cervical intraepithelial neoplasia in married women from Beijing / 中华流行病学杂志

Objective To investigate the prevalence and relationship between high risk human papillomavirus(HR-HPV)and cervical intraepithelial neoplasia(CIN)in married women from Beijing.Methods From March 2007 to September 2008,a total of 6185 married women were sampled,covering 137 communities in 12 districts.The samples were screened by high-risk HPV DNA test(HC2)and cytological test.For those participants with cytological test results≥ASCUS,pathological tests were performed.An interview was also carried out with the same questionnaire.Results from the tests were inputted into the database twice using EpiData 3.0,reviewed,analyzed,using SPSS 15.0.Results(1)The prevalence rates of HR-HPV and CIN were 9.9% and 6.0%,respectively for the age group 25 to 54.(2)The peak age groups for HR-HPV and CIN prevalence rates were 30 to 34 years old.(3)The prevalence rates of positive cytology(40.3%)and CIN (30.4%)in HR-HPV positive female population were significantly higher than that in HR-HPV negative group.(4)Data from unconditional logistic regression analysis showed that,when comparing with the normal subjects,the risk odds ratios of HR-HPV with low grade CIN and cervical cancer/high grade CIN were 8.385 and 97.416 and the attributable risk proportions with these groups were 88.1% and 99.0%,respectively.Conclusion HR-HPV infection seemed to be the main risk factor for CIN.Married women,from age group 30-34,were under the high risk group in both HR-HPV infection and CIN incidence.