Comparison of milk protein concentrate, micellar casein, and whey protein isolate in loading astaxanthin after the treatment of ultrasound-assisted pH shifting.

Milk proteins can be used as encapsulation walls to increase the bioavailability of active compounds because they can bind hydrophobic, hydrophilic, and charged compounds. The objective of this study was to investigate the effects of astaxanthin (ASTA) encapsulation and the functional properties of milk protein and ASTA nanocomposites by an ultrasound-assisted pH-shifting treatment of different milk proteins, including milk protein concentrate (MPC), micellar casein (MCC), and whey protein isolate (WPI). The ultrasound-assisted pH-shifting treatment of milk protein helped to improve the encapsulation rate of ASTA. Therein, MCC showed great improvement of encapsulating ASTA after co-treatment with the raised encapsulated rate of 5.11%, followed by WPI and MPC. Furthermore, the nanocomposites of ASTA with milk protein exhibit improved bioavailability, antioxidant capacity, and storage stability. By comparison, MCC-encapsulated ASTA has the best storage stability, followed by MPC, and WPI-encapsulated ASTA has the least stability over a 28-d storage period. The results of intrinsic fluorescence and surface hydrophobicity showed that milk protein underwent fluorescence quenching after binding to ASTA, which was due to the hydrophobic sites of the protein being occupied by ASTA. In general, the nanocomposites of milk protein and ASTA fabricated by using an ultrasound-assisted pH-shifting treatment have the potential to be better nano-delivery systems for ASTA in functional foods, especially MCC, which showed excellent performance in encapsulation after treatment technique.

[Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases].

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

[Application of entropy weight TOPSIS comprehensive method in the evaluation of students' physical health level].

Objective: To comprehensively evaluate the physical health level of students of different school-age segments in four regions of Anhui province using the entropy weight approximation ideal solution ranking method (TOPSIS), and to provide a scientific method and basis for conducting school health work evaluation. Methods: Using the physical fitness survey data of four regions in Anhui province, the entropy weight method was used to draw the weights of various indicators for different school-age segments of men and women. Then, the TOPSIS method was used to evaluate the school-age segments of men and women in the four regions. Finally, the physical health level of students in four regions was classified according to the results of entropy weight TOPSIS and the rank sum ratio method. Results: A total of 10 127 students were included in this study, with an average age of (11.85±3.82) years, including 5 050 males (49.8%) and 5 072 urban students (50.1%). The results of the entropy weight method showed that the weight of body mass index of boys was similar to that of girls in each school-age segment. According to the TOPSIS and rank sum ratio analysis, the physical health level of students in the four regions of Anhui province was different. The physical health score of Suzhou was 0.617 4 points, which was classified as the best grade. The scores of Hefei and Wuhu were 0.556 3 and 0.411 2, which were classified as middle. Jiju City scored 0.381 9 points, which was classified as poor. Conclusion: TOPSIS combined with rank sum ratio can reflect the level of students' physical health, which can be applied to the evaluation of students' physical health and provide a basis for monitoring students' physical health.

[Analysis of surgical treatment of severe angular kyphosis with keeping the spinal cord length constant in osteotomy area].

Objective: To explore the surgical methods and clinical outcomes of severe angular kyphosis with the length of the spinal cord constant in the osteotomy area. Methods: Clinical data from 20 patients with severe angular kyphosis who underwent surgical treatment from January 2017 to December 2020 in the Department of Spinal Surgery,Hangzhou Xiaoshan District Hospital of Traditional Chinese Medicine were retrospectively analyzed. There were 11 males and 9 females, aged (28.5±8.9) years (range:17 to 46 years).There were 15 cases with congenital angular kyphosis,5 cases with tuberculous angular kyphosis.The angle of kyphosis was (107.1±12.9)° (range:93.2° to 131.4°).Frankel classification:2 cases with grade B,4 cases with grade C,3 cases with grade D.The kyphotic vertex is located at the T9 to T12 segments.Pedicle screws were placed in 3 or 4 adjacent segments at the proximal and distal kyphosis apex of the patients using a surgical navigation system.Piezosurgery combined with a grinding drill was used to complete the osteotomy in the apical vertebral region.Titanium mesh or artificial vertebral body was implanted,and the osteotomy surface was closed using this as the fulcrum to complete osteotomy.Spinal X-ray examination was performed before surgery,immediately after surgery and at the last follow-up,and sagittal and coronal Cobb angle,sagittal and coronary balance parameters,anterior vertebral height,posterior vertebral height,and spinal cord length were measured.Pulmonary function,visual analogue scale (VAS),and Oswestry's disability index (ODI) were collected and estimated before and after treatment.The analysis of variance of repeated measurement data was used for each evaluation index before and after treatment,and the t test was used for pairwise comparison. Results: All patients successfully completed surgery,with artificial vertebral body in 11 cases and double titanium mesh in 9 cases.The follow-up time was (28.2±2.3) months (range:26 to 31 months).Sagittal vertical axis improved from (46.9±13.7)mm(range:21.7 to 75.7 mm) before surgery to (10.7±5.5)mm (range:3.6 to 28.1 mm) after surgery,and (11.0±5.7)mm(range:3.6 to 29.3 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The mean kyphotic Cobb angle was corrected from (107.1±12.9) ° (range:93.2 ° to 131.4°) before surgery to (30.6±8.5) ° (range:20.0 ° to 47.8 °) after surgery (all P<0.01),and (32.1±8.7) ° (range:18.2 ° to 50.8°) at the last follow-up,the differences were statistically significant compared to before surgery(all P<0.01).The anterior vertebral height improved from (14.2±2.9)mm(range:11.04 to 23.6 mm) before surgery to (45.3±7.5)mm(range:29.4 to 56.5 mm) after surgery,and (44.3±6.8)mm(range:29.6 to 56.0 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The posterior vertebral height was improved from (51.8±5.3)mm (range:43.1 to 61.4 mm)before surgery to (57.6±4.7)mm (range:45.7 to 64.1 mm)after surgery,and (56.3±5.0) mm (range:49.7 to 68.5 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The spinal cord length of the osteotomy segment was (73.1±12.0)mm (range:56.8 to 98.4 mm) before surgery and (74.8±12.8)mm (range:53.5 to 100.2 mm) after surgery and (75.2±13.7)mm (range:53.9 to 102.4 mm) at the last follow-up,the difference was not statistically significant among them(F=0.144,P=0.866).The ODI and VAS scores improved significantly after surgery and at the last follow-up,and the differences were statistically significant (all P<0.01). Conclusion: The posterior vertebral column resection technique combined with titanium mesh or an artificial vertebral body implant for the treatment of severe angular kyphosis can significantly improve the kyphosis,neurological function,and life quality of patients without affecting the length of the spinal cord.

[Standardized implementation of multi-disciplinary treatment to improve the overall efficacy of pancreatic cancer].

The incidence and mortality of pancreatic cancer are increasing year by year worldwide, but the effect of prevention and treatment is not ideal. The standardized implementation of multi-disciplinary treatment (MDT) can make the diagnosis of pancreatic cancer more clear and more accurate clinical staging, surgical resection rate can be improved and the ratio of adjuvant chemotherapy and other comprehensive treatment can be improved, the treatment mode of pancreatic cancer can be optimized, combined with individual differences of patients, and to develop a comprehensive and personalized treatment plan. The standardized development of MDT is simple, fast and economical, and has the optimal health economic value.

[Impacts of glycemic variability on the relationship between time in range and estimated glycated hemoglobin in patients with type 1 diabetes mellitus].

Objective: This study is to investigate the relationship between time in range (TIR) and glucose management indicator (GMI), and the impact of glycemic variability (GV) on their relationship in patients with type 1 diabetes mellitus (T1DM). Methods: The CGM data were collected from a multicenter randomized clinical trial of adults (≥18 years old) with T1DM, including 83 T1DM patients, respectively from the Third Affiliated Hospital of Sun Yat-sen University (72 cases), Drum Tower Hospital Affiliated to Nanjing University School of Medicine (2 cases), and the First Affiliated Hospital of University of Science and Technology of China (9 cases). All subjects wore the iProTM2 system for 14 days at baseline (0-2 weeks), 3 months (12-14 weeks), and 6 months (24-26 weeks). Data derived from iProTM2 sensor was used to calculate CGM parameters. Correlation between TIR and GMI was explored according to different stratification of glycemic variability assessed by glucose coefficient of variation (CV). Predicted TIR in the fixed GMI value was calculated via the linear regression equations performed in the respective interquartile group of CV. Results: From November 2017 to June 2021, a total of 233 CGM data were collected with 83 collected from baseline, 80 from the 3-month follow-up, 70 from the 6-month follow-up. Patients including 27 males had a median (Q1, Q3) age of 30.69 (25.22, 38.43) years, with a diabetes duration of 10.05(4.46, 13.92) years. The median (Q1, Q3) and effective wearing time of available CGM data was 13.92 (13.02, 14.00) days and 91.61% (84.96%, 95.94%), and the value of TIR, GMI and CV was 60.34%±13.03%, 7.14%±0.61% and 41.01%±7.64%, respectively. There was a strong negative correlation between TIR and GMI (r=-0.822, P<0.001). Multiple linear regression analysis showed that the predictive value of TIR calculated from a given GMI was 8.352% higher when CV was up to standard (36%) than that when CV was down to standard. Based on the multiple linear regression equations generated from quartiles of CV, the predicted TIR value was decreased across the ascending quartiles with 69.98 % in the lowest quartile of CV (≤35.91%), 64.57 % in 25th-50th quartile of CV (35.91%75th quartile, CV>45.86%) when GMI was set as 7%. Conclusions: There is a strong correlation between TIR and GMI in adult patients with T1DM in patients with type 1 diabetes mellitus. CV influenced the relationship between TIR and GMI.

[New understanding and research opportunities of metabolically healthy obesity].

The paradox of obesity and metabolically healthy obesity are being challenged. More and more studies have disputed the potential mechanism and prognostic value of metabolically healthy obesity. The study of metabolically healthy obesity is helpful to clarify the potential causes of obesity paradox and the potential mechanism of different degrees of obesity harm to the population. From the perspective of evidence-based medicine, combined with the relevant literature at home and abroad, this study reviewed the new understanding of metabolically healthy obesity, lifestyle factors, the impact of fat factors on metabolically healthy obesity, and the new opportunities of metabolically healthy obesity research, in order to explore whether metabolically healthy obesity can maintain and gradually reduce weight for a long time, so as to improve cardiovascular disease In order to achieve the purpose of primary prevention of related diseases.

[Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma].

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

Physicochemical and functional properties of goat milk whey protein and casein obtained during different lactation stages.

During lactation, goat milk contains colostrum, transitional milk, mature milk, and end milk. The protein present in goat milk during different lactation periods has different characteristics. This study aimed to characterize the protein profile of goat milk samples obtained at different lactation stages and to identify changes in the physicochemical and functional properties of whey protein and casein from goat milk collected at 1, 3, 15, 100, and 200 d after calving. The results demonstrated that the lactation period had a great influence on the physicochemical and functional properties of goat milk whey protein and casein, especially the protein properties of colostrum on the first day after delivery. The denaturation temperature, hydrophobicity, and turbidity of whey protein were significantly higher on the first day postpartum than at other lactation periods. Correspondingly, the colostrum whey protein also had better functional properties, such as emulsification, oil holding capacity, and foaming properties on the first day postpartum than at other lactation periods. For casein, the turbidity, particle size, water holding capacity, and foaming properties on the first day after delivery were significantly higher than those at other lactation periods, whereas the denaturation temperature, oil holding capacity, and emulsification followed the opposite trend. For both whey protein and casein, the 2 indicators of emulsifying properties, namely, emulsifying activity index and the emulsion stability, also followed an opposite trend relative to lactation stage, whereas the changes in foaming capacity with the lactation period were completely consistent with the change of foaming stability. These findings could provide useful information for the use of goat milk whey protein and casein obtained during different lactation stages in the dairy industry.

[Long-term survival should be regarded as the ultimate goal of pancreatic cancer surgery].

The incidence and mortality of pancreatic cancer are increasing year by year worldwide, but the prevention and treatment effect is far from satisfactory. Surgical resection remains the main treatment for pancreatic cancer, but the advantages and disadvantages of surgery are clear. How to avoid the disadvantages and maximize the advantages of surgery to optimize the benefits of patients contributes the main criteria for judging whether the operation for pancreatic cancer is successful or not. In order to achieve the success of pancreatic cancer surgery, perioperative attention must be paid to the comprehensive factors including tumor, host and surgical team, especially to fully understand the limitation of TNM staging,and to emphasize the individualized comprehensive diagnosis and treatment protocol under the guidance of standardized multidisciplinary team (MDT) mode, with long-term survival as the ultimate goal of being a qualified surgical oncologist.

[Analysis of clinical features of cervical precancerous lesions in postmenopausal women].

Objective: To analyze the characteristics of high-grade squamous intraepithelial lesion (HSIL) diagnosed by cervical tissue sampling in postmenopausal women. Methods: A retrospective study was performed on 2 013 patients with HSIL diagnosed by cervical tissue sampling under colposcopy and treated by cervical conization at the First Affiliated Hospital of Zhengzhou University from June 2017 to November 2018, to compare the difference of patients' clinical features, HPV test, liquid-based thin-layer cytology (TCT), performance of colposcopy and biopsy pathology, pathology after cervical conization between 439 postmenopausal patients and 1 574 pre-menopausal patients. Results: (1) Clinical features: the proportion of contact bleeding showed no significant difference between postmenopausal patients and pre-menopausal patients [4.3% (19/439) vs 6.4% (101/1 574); χ²=2.672, P=0.102]. Among the patients with contact bleeding, the proportion of cervical cancer after cervical cone resection was significantly higher in postmenopausal patients compared with pre-menopausal patients [10/19 vs 22.8% (23/101); χ²=7.157, P=0.007]. Among the patients found by routine screening, the proportion of cervical cancer after cervical cone resection was significantly higher in postmenopausal patients compared with pre-menopausal patients [9.0% (38/420) vs 4.3% (63/1 473); χ²=14.726, P<0.01]. The proportion of smooth cervix was higher in postmenopausal patients compared with pre-menopausal patients [63.6% (279/439) vs 35.5% (558/1 574); χ²=111.601, P<0.01]. (2) High-risk HPV infection: there was no significant difference in the high-risk HPV positive rate between the postmenopausal group and the pre-menopausal group [92.0% (404/439) vs 94.4% (1 486/1 574); χ²=3.394, P=0.065]; the HPV 16 infection was the most common type, but there was no significant difference in the HPV 16 infection rate between the two groups [65.8% (289/439) vs 68.0% (1 070/1 574); χ²=0.722, P=0.395]. (3) TCT test: TCT test results included negative for intraepithelial lesion and malignancy (NILM), atypical squamous cell of undetermined signification (ASCUS), atypical squamous cells cannot exclude high-grade lesion (ASC-H), low grade squamous intraepithelial lesion (LSIL), HSIL, compared with the different results of TCT examination, there were not statistically significant difference between postmenopausal and pre-menopausal patients (all P>0.05). (4) The performance of colposcopy: the proportion of insufficient colposcopy and the proportion of cervical type Ⅲ conversion area were higher in postmenopausal patients compared with pre-menopausal patients [87.5% (384/439) vs 32.5% (511/1 574), P<0.01; 80.0% (351/439) vs 21.9% (344/1 574), P<0.01]. The proportion and positive rate of endocervical curettage (ECC) in postmenopausal patients were higher than those in pre-menopausal patients [35.3% (155/439) vs 20.4% (322/1 574), P<0.01; 67.7% (105/155) vs 53.1% (171/322), P=0.003]. The proportion of lesions involving the vaginal wall was higher in postmenopausal patients compared with pre-menopausal patients [5.9% (26/439) vs 1.0% (16/1 574); χ²=40.443, P<0.01]. There was a positive correlation between vaginal wall lesions and cervical lesions in postmenopausal patients (r=0.660, P<0.01). (5) Postoperative pathology: the positive rate of margin and the proportion of pathological escalation after cervical conization were significantly higher in postmenopausal patients compared with pre-menopausal patients [14.6% (64/439) vs 4.8% (75/1 574), 10.9% (48/439) vs 5.5% (86/1 574); P<0.01]. Conclusions: Colposcopy in postmenopausal women is often inadequate, and the cervix is mostly type Ⅲ transformation zone. The lesion in postmenopausal women is more likely to involve the cervical canal and vaginal wall. Clinical attention should be paid to cervical tube curettage and comprehensive examination of the vaginal wall. The high rate of positive margins and a high proportion of pathological upgrading after cervical conization in postmenopausal patients requires further active intervention.

[Healthy life expectancy for registered residents in 2017 in Shanghai Jing'an Districts].

Objective: To estimate the healthy life expectancy (HALE) of registered residents in Jing'an District, Shanghai City. Methods: From June to August in 2017, 14 districts (towns) were selected as the research sites, and 4 159 registered residents were selected as the subjects. The health status data of subjects were collected by using the self-rated health scale, and the health rate of subjects was obtained by using the CHOPIT model. The health rate of residents under 18 years old was replaced by the parameters of 18-year-old group, and Sullivan method was used to calculate the HALE of registered residents in Jing'an District, Shanghai City. Results: The age of 4 159 subjects was (56.46±15.19) years old, ranging from 18 to 98 years old. There were 1 768 males (42.5%). The overall health rate of subjects was 74.96%, of which the health rates of male and female were 76.87% and 72.45% respectively. With the increase of age, the health rate decreased (Z=265.51, P<0.001), and the health rate of male was higher than that of female (χ²=2 154.54, P<0.001). The HALE of the 0-year-old group was 64.29 years old, in which the male and female were 66.25 and 63.57 years old respectively. Among the 18-year-old group, the HALE was 48.18 years old, with 49.07 years old for male and 47.46 years old for female. The HALE of male was higher than that of female in all age groups. With the increase of age, the HALE decreased gradually. Conclusion: There are significant sex and age differences in HALE in Jing'an District, Shanghai City. The health issue of female and older people should be given more attention.

[Inflammatory myofibroblastic tumors of the urinary bladder: a clinicopathological study of ten cases].

0bjective To investigate the clinicopathological features,immunohistochemical phenotypes, molecular genetic alterations,diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Methods: Ten cases of IMT of the urinary bladder (three cases at Ningbo Diagnostic Pathology Center from September 2011 to December 2020, five in-house diagnosed cases and two consultation cases at Shanghai Rui Jin Hospital from June 2011 to December 2020) were collected retrospectively. The clinicopathologic features and immunophenotypic profiles were studied by light microscopy and immunohistochemistry (EnVision method). The translocation of ALK gene was detected by fluorescence in situ hybridization (FISH). Results: Of the 10 patients, eight were male and two were female. The patients' age range was 16 to 62 years (median 36 years).The main clinical presentation was hematuria and urinary irritation. Three cases were located at the dome of the urinary bladder, four cases were in the left lateral wall and the remaining three cases were in the right lateral wall. The tumor size ranged from 1.5 cm to 8.5 cm. In eight cases, the tumors were mainly submucosal, and in some cases extending to the muscular layer of the urinary bladder. In two cases, the tumors were mainly located in the muscular layer and focally extended to the submucosa and adventitia. Histologically, four cases had the nodular fasciitis-like pattern, three cases had fibrohistiocytoma-like pattern, two cases had mixed histologic patterns and the remaining case showed leiomyosarcoma-like histologic features. Immunohistochemically, the tumor cells expressed SMA (10/10),calponin (9/10),desmin (6/10) and CKpan (9/10). Cytoplasmic staining for ALK1 and ALK (5A4) was detected in 7 of 10 cases and 8 of 10 cases, respectively. Nuclear and cytoplasmic staining for ALK (D5F3) was detected in 7 of 10 cases. Among eight cases with material available for FISH analysis, ALK rearrangement was present in five cases. Follow-up data were available in eight patients and none had local recurrence nor distant metastasis. Conclusion: IMT of the urinary bladder is an uncommon mesenchymal neoplasm with intermediate malignant potential.It has special clinicopathologic features, and a minority of cases have local tumor recurrence.

Age-Related Changes of Material Mechanics and Bone Material Parameters of Rat Skulls.

ABSTRACT: Objective To study the relationship between material mechanics and bone material parameters of rat skulls and their correlation with age by examination of the parameters. Methods Forty-eight healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52 and 104 week groups according to their age. Each group had six rats. The right cranium was compressed by KD Ⅱ-0.2 microcomputer controlled electronic universal testing machine, and material mechanics parameters （ultimate load, compression strength and compression modulus） were measured, then the skull slices were cut off and scanned by Micro-CT system to detect bone material parameters （skull thickness, bone mineral density, bone volume, and trabecular thickness）. Results The differences in ultimate load, compression strength and compression modulus among all groups had statistical significance （P<0.05）, and were positively correlated with age within 26 weeks （P<0.05）. The differences in skull thickness, bone mineral density, bone volume and trabecular thickness among all groups had statistical significance （P<0.05）, and were positively correlated with age within 52 weeks （P<0.05）. All material mechanics parameters were positively correlated with bone material parameters （P<0.05）. Conclusion There is a positive correlation between bone material parameters （skull thickness, bone mineral density, bone volume, trabecular thickness）, material mechanics parameter （skull ultimate load, compression strength, compression modulus） and age in a certain range, which can be used to infer age.

The histone deacetylase inhibitor chidamide induces intermittent viraemia in HIV-infected patients on suppressive antiretroviral therapy.

OBJECTIVES: To evaluate the safety and efficacy of chidamide to reverse HIV-1 latency in vivo and to compare the effects of four clinically tested histone deacetylase (HDAC) inhibitors on non-histone proteins in vitro. METHODS: Participants received chidamide orally at 10 mg twice weekly for 4 weeks while maintaining baseline antiretroviral therapy. The primary outcome was plasma viral rebound during chidamide dosing and the secondary outcomes were safety, pharmacokinetic and pharmacodynamic profiles, changes in cell-associated HIV-1 RNA and HIV-1 DNA, and immune parameters. Western blotting was used to compare the in vitro effects of the four HDAC inhibitors on HSP90, NF-κB and AP-1. RESULTS: Seven aviraemic participants completed eight oral doses of chidamide, and only grade 1 adverse events were observed. Cyclic increases in histone acetylation were also detected. All participants showed robust and repeated plasma viral rebound (peak viraemia 147-3850 copies/mL), as well as increased cell-associated HIV-1 RNA, during chidamide treatment. Furthermore, we identified an enhanced HIV-1-specific cellular immune response and a modest 37.7% (95% CI: 12.7-62.8%, P = 0.028) reduction in cell-associated HIV-1 DNA. Compared with the other three HDAC inhibitors, chidamide had minimal cytotoxicity in vitro at clinically relevant concentrations and showed mechanistically superior effects on non-histone proteins, including HSP90, NF-κB and AP-1. CONCLUSIONS: Chidamide safely and vigorously disrupts HIV-1 latency in vivo, which makes it a promising latency-reversing agent.

Change in the structural and functional properties of goat milk protein due to pH and heat.

This study was carried out to investigate the effects of pH and heat on the structure and function of milk proteins by comparing goat milk treated under different pH and temperature conditions. The results showed that pH had a significant effect on the thermal stability of goat milk proteins, and the proteins were least thermally stable at pH 7.7. Except for the pH 6.9 goat milk, the surface hydrophobicities of the milk proteins at various pH values reached their maxima at 85°C. The particle size, zeta potential, and content of regular secondary structure also decreased significantly at 85°C, and the turbidity of milk proteins under alkaline pH conditions was lower than that under acidic conditions. It was concluded that alkaline conditions resulted in better emulsion stability and oil-holding capacity, and acidic conditions offered better foaming ability, foam stability, and water-holding capacity for goat milk protein during heat processing. It can also be seen that 85°C was the key temperature for milk proteins after changing the pH of the milk. This paper provides a theoretical basis for optimizing the processing conditions for goat milk and the applications of goat milk proteins.

[Diagnosis, treatment and prognosis evaluation of pancreatic cancer by microRNA].

Pancreatic cancer, with the characteristics of insidious onset, easy metastasis, chemotherapy resistance and poor prognosis, is a common malignant tumor of the digestive system. Early diagnosis and treatment of pancreatic cancer is one of the major problems in modern medicine, and there is an urgent need to find new diagnostic, prognostic biomarkers and therapeutic targets. MicroRNA (miRNA) is a small non-coding RNA which can regulate the expression of various genes. miRNAs have wide abnormal expressions in pancreatic cancer, and are closely related to the occurrence and development of pancreatic cancer. Thereby, miRNAs have the potential to become new diagnostic, prognostic and predictive biomarkers and therapeutic targets of pancreatic cancer. Many studies have initially shown that miRNAs have the application value in the diagnosis, treatment and prognosis evaluation of pancreatic cancer, but there are still some difficulties in the practical application and promotion. The mechanisms of miRNAs in pancreatic cancer remain to be further studied.

[The relationship between the index of lymph node metastasis and the prognosis of pancreatic cancer patients after R0 resection].

Objective: To investigate the prognostic values of three different staging schemes including the number of lymph node metastasis (N stage), lymph node ratio (LNR) and log odd of positive lymph nodes (LODDS) in pancreatic cancer patients after R0 resection. Methods: The clinical and pathological data of 307 pancreatic cancer patients who underwent R0 resection at Cancer Hospital of Chinese Academy of Medical Sciences from January 2010 to December 2018 were retrospectively analyzed. Kaplan-Meier and Cox proportional hazard regression models were used to analyze the independent prognostic factors. The area under the receiver operator characteristic curve (AUC) was used to compare the prognostic efficacy of different lymph node staging systems. Results: The median survival was 24.0 months, 1-year, 3-year, and 5-year survival rates were 72.0%, 35.5% and 24.0%, respectively. Multivariate analysis showed that CA199, differentiation, T stage, adjuvant therapy, N stage, LNR stage, and LODDS stage were independent prognostic factors for pancreatic cancer patients after R0 resection (P<0.05). The AUC values of the 1-year survival rate for N stage, LNR stage, and LODDS stage were 0.591, 0.592 and 0.609, respectively. The AUC values of the 3-year survival rate for N stage, LNR stage, and LODDS stage were 0.585, 0.588 and 0.593, respectively. The AUC values of the 5-year survival rate for N stage, LNR stage, and LODDS stage were 0.554, 0.557 and 0.589, respectively. The AUC values of the LODDS stage were the highest while the N stage were the lowest, but there was no significant difference among these three systems (P>0.05). For all patients, the LODDS staging system was slightly better than the N and LNR staging systems, but the difference was not statistically significant (P>0.05). For patients with N0 stage, the LODDS staging system showed better prediction performance than the N stage and LNR staging systems (P<0.05). Conclusions: The N stage, LNR stage, and LODDS stage are independent prognostic factors for pancreatic cancer patients after R0 resection. For patients without lymph node metastasis, LODDS staging system is superior to N and LNR staging systems in predicting prognosis.

[Learning curve analysis of 73 cases of central pancreatectomy].

Objective: To explore the learning curve of central pancreatectomy (CP) and provide an excellent reference for surgeons to get the point of this operation. Methods: Clinical data of 73 patients who underwent CP in the same operation team from January 2006 to January 2018 were collected and retrospectively analyzed by the moving average method (MAM) and the cumulative sum method (CUSUM). Data was analyzed by statistical package for social science (SPSS) software. Results: According to the MAM and CUSUM curves, the learning process of CP could be divided into two stages. At the first stage (n=1-11), the median operation time was 340 minutes and the median intraoperative hemorrhage was 400 ml. In the second stage (n=12-73), the median operation time was 213 minutes and the median intraoperative hemorrhage was 100 ml. The difference was statistically significant (P<0.001). There were no significant differences between the two stages of patients in terms of other aspects (P>0.05). Conclusions: CP can be mastered after 11 cases of exercises. In the first 11 operations, surgeons should get familiar with the operation process, respond actively to emergencies and accumulate experience to gain this surgical technique fast.

[Clinicopathological features of de novo CD5-positive diffuse large B-cell lymphoma].

Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,ß2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.