Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism.@*METHODS@#MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts.@*RESULTS@#MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight.@*CONCLUSION@#LCA is capable of inhibiting the proliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Lenvatinib down-regulates IGF1R/Mek/Erk signaling pathway in the treatment of regorafenib-resistant hepatocellular carcinoma / 中华肿瘤杂志

Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.

Normative wideband absorbance measures in children: a cross-sectional study / 中华耳鼻咽喉头颈外科杂志

Objective: This study was to investigate the main characteristics and related factors of wideband absorbance (WBA) in children with normal hearing and to obtain age-specific reference range of WBA. Methods: 384 children between 0-12 years old (615 ears) who visited the Beijing Children's Hospital, Capital Medical University from October 2019 to February 2021 were enrolled, including 230 males (376 ears) and 154 females (239 ears), with totally 306 left ears and 309 right ears. Wideband tympanometry (WBT) was performed and normative WBA data were analyzed by SPSS 24.0 statistical software. Repeated measures and multivariate analysis of variance were applied to the data from 16 points at 1/3-octave frequencies (226, 324, 408, 500, 667, 841, 1 000, 1 297, 1 682, 2 000, 2 670, 3 364, 4 000, 5 339, 6 727 and 8 000 Hz) to evaluate the effects of frequency, age, external auditory canal pressures, gender and ear on WBA. Results: According to the WBT frequency-absorbance curve, the subjects were divided into seven groups: 1-month old group, 2-month old group, 3-month old group, 4-5 month old group, 6-24 month old group,>2-6 year old group and>6-12 year old group. The WBA of normal-hearing children underwent a series of developmental changes with age at both ambient pressure and tympanometric peak pressures. WBA results for 1-month group and 2-month old group exhibited a multipeaked pattern, with the peaks occurring around 2 000 and 4 897 Hz, and a notch around 3 886 Hz. WBA results for 3-month group and 4-5 month old group exhibited a single broad-peaked pattern, with the peak occurring between 2 000-4 757 Hz. The WBA of 1-month old group to 4-5 month old group decreased gradually at low frequency (226-408 Hz) and 6 727 Hz, and increased at middle to high frequency (2 670-4 000 Hz). The WBA of 6-24 month old group were significantly lower than that of 2-month old group to 4-5 month old group at all frequencies except 3 364 and 4 000 Hz. WBA results for 6-24 month old group,>2-6 year old group and>6-12 year old group exhibited a single-peaked pattern, and the peak frequency of WBA moved to the lower frequency successively. From 6-24 month old group to>6-12 year old group, the WBA gradually increased at low to middle frequencies (667-2 670 Hz) and 8 000 Hz, and decreased at middle to high frequencies (3 364-5 339 Hz). Among the 16 frequencies of all age groups, the difference between WBA under ambient pressure and tympanometric peak pressure were -0.09-0.06, and 43.75%-81.25% frequency points had statistically significant difference, which was mainly manifested in that WBA under ambient pressure were lower than that under tympanometric peak pressure at 226-1 682 Hz. There was no significant ear effect on all of the age groups. Similarly, there was no significant gender effect except for 3-month old group and 4-5 month old group. Conclusions: The WBA of normal-hearing children measured at ambient pressure and tympanometric peak pressure varied across the frequencies with age from 1 month to 12 years old, and different frequencies followed different change patterns (increase vs. decrease) in WBA. There was also significant external auditory canal pressures effect on all of the age groups. The establishment of age-specific reference range of WBA for 0-12 years old normal-hearing children in this study would be useful for clinical practice of determining normative data regarding WBT.

Study on the predictive significance of PLR, SII and RPR in ovarian endometriotic cyst / 中华妇产科杂志

Objective: To investigate the predictive value of platelet-to-lymphocyte ratio (PLR), red blood cell distribution width to platelet count ratio (RPR) and systemic immune inflammation index (SII) in the staging and postoperative recurrence of ovarian endometrial cysts. Methods: Retrospective analysis was made on the clinical data of patients who underwent laparoscopic surgery for ovarian cysts in the Affiliated Hospital of Qingdao University from January 2018 to January 2020. The patients with ovarian endometriosis cyst confirmed by pathology after surgery were the observation group (n=350), and the patients with other benign ovarian cyst were the control group (n=150). The preoperative platelet count, platelet distribution width, absolute number of neutrophils, lymphocyte absolute number, absolute number of monocytes, red blood cell distribution width, and serum cancer antigen 125 (CA125) of the patients in two groups were recorded, and PLR, neutrophil-to-lymphocyte ratio (NLR), RPR, SII, and systemic inflammation response index (SIRI) were calculated and analyzed. The general data of all patients and the follow-up data within 2 years after the operation of the observation group were statistically recorded to evaluate the diagnostic value of PLR, RPR and SII for ovarian endometrial cyst, and the predictive value of staging and recurrence within 2 years after the operation. Results: PLR, NLR, SII (median: 147.53, 1.86, and 488.70 respectively) and CA125 (median: 59.41 kU/L) in the observation group were significantly higher than those in the control group, while RPR (median: 0.16) was lower than that in the control group, with significant differences (all P<0.01). There was no significant difference in SIRI between the two groups (P>0.05). The PLR and SII (median: 122.73, 345.00) of the observation group at stage Ⅲ and Ⅳ were higher than those of patients at stage Ⅰ and Ⅱ, and the RPR was lower than that of patients with stage Ⅰ and Ⅱ, with significant differences (all P<0.001). The PLR, NLR, SII, SIRI (median: 179.63, 2.75, 762.96, and 1.06 respectively) and CA125 (median: 108.83 kU/L) in patients with recurrence were significantly higher than those in patients without recurrence 2 years after the operation, and the differences were statistically significant (all P<0.001). The area under curve (AUC) of CA125 in the diagnosis of ovarian endometriosis cyst was 0.951, the sensitivity was 85.7%, and the specificity was 93.0%, which were higher than those of PLR and SII; the AUC of PLR+SII+CA125 in the diagnosis of ovarian endometriosis cyst was 0.952. The AUC of RPR predicting the stage of ovarian endometriosis cyst was 0.713, higher than PLR and SII, lower than CA125; the AUC of RPR+SII+CA125 in predicting the stage of ovarian endometriotic cyst was 0.825, with sensitivity of 68.7% and specificity of 85.7%. The AUC predicted by SII for recurrence of ovarian endometriotic cyst within 2 years after the operation was 0.803, higher than NLR, PLR, SIRI and CA125; the AUC of PLR+SII+CA125, sensitivity, specificity was 0.813, 81.5% and 73.0%, higher than SII. Conclusion: PLR, RPR and SII are related to the staging of ovarian endometriotic cyst, and SII has a certain predictive value for the recurrence of ovarian endometriotic cyst after surgery.

Licochalcone A inhibits osteosarcoma proliferation by Akt/ERK signaling pathway / 中国药理学通报

Aim To investigate the effect of licochalcone A (LCA) on proliferation and apoptosis of osteosarcoma HOS and U2OS cells and to explore its possible molecular mechanism. Methods The HOS and U2OS cells were cultured in vitro. MTT assay was used to detect the proliferation of the cells after being treated with different concentrations of LCA at different intervention time. Then HOS and U2OS cells were treated with 0. 1% DMSO, or different concentrations of LCA (5, 10, 20 μmol/L), and flow cytometry was used to assess the cell apoptosis. The expression of apoptosis-related protein cleaved PARP1, Bcl-2, Bax, and Akt, ERK were detected by Western blot. The antitumor effect of LCA was detected on U2OS xenograft mice in vivo. Results LCA could inhibit the proliferation of HOS and U2OS cells in a time-and dose-dependent manner. Flow cytometry showed that LCA treatment could induce cell apoptosis. Western blot results showed that LCA could inhibit the phosphorylation of Akt and ERK, increase the expression of cleaved PARP1 and Bax, and decrease the expression of Bcl-2. In the tumor-bearing mouse models, LCA significantly decreased the tumor volume (P < 0. 05) and weight (P < 0. 01). Conclusions LCA could inhibit the proliferation of HOS and U2OS and induce apoptosis possibly by inhibiting the Akt/ERK signaling pathway.

Effects of miR-515-5p on the proliferation and metastasis of ovarian cancer cell A2780 by regulating the expression of chondroitin sulfate proteoglycan 4 and its mechanism / 解剖学报

Objective To investigate the targeted regulation of miR-515-5p on chondroitin sulfate proteoglycan 4 (CSPG4) and its effect on the proliferation and metastasis of ovarian cancer cell A2780. Methods The target genes of miR-515-5p were predicted by bioinformatics tools. Real-time PCR and Western blotting were used to detect the expression of miR-515-5p and CSPG4 in 65 cases ovarian cancer tissues and adjacent tissues. Ovarian cancer cells A2780 were divided into miR-NC group, miR-515-5p group, si-NC group, si-CSPG4 group, miR-515-5p + pcDNA group, miR-515-5p + pcDNA-CSPG4 group. MTT assay was used to detect cell proliferation. Transell was applied to detect cell migration and invasion, and Western blotting was selected to detect cyclinD1, P21, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. The double luciferase reporter gene experiment and Western blotting confirmed the regulation effect of miR-515-5p on CSPG4 gene. Results Bioinformatics analysis showed that CSPG4 was one of the potential target genes of miR-515-5p. Compared with the adjacent tissues, the expression of miR-515-5p was lower in ovarian cancer tissues, and the expression of CSPG4 was higher (P< 0. 05). Compared with the miR-NC group, the expression of cyclinD1, MMP-2 and MMP-9 protein was lower in A2780 cells of miR-515-5p group, the expression of P21 protein was higher, the cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the si-NC group, the expression of cyclinD1, MMP-2 and MMP-9 proteins were lower in A2780 cells in si-CSPG4 group, P21 protein was higher, cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the miR-515-5p + pcDNA group, the expression of cyclinD1, MMP-2 and MMP-9 proteins was higher in A2780 cells of miR-515-5p + pcDNA-CSPG4 group, the expression of P21 protein was lower, and the cell viability was higher, the number of cell migration and invasion was higher (P<0. 05). MiR-515-5p targeted and negatively regulated CSPG4 expression. Conclusion MiR-515-5p could inhibit the proliferation and metastasis of ovarian cancer cell A2780 by targeting CSPG4.

Efficacy and safety of a parylene-coated occluder for atrial septal defect: a prospective, multi-center, randomized controlled clinical trial / 中华医学杂志(英文版)

BACKGROUND@#Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD).@*METHODS@#One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.@*RESULTS@#At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P  0.05).@*CONCLUSIONS@#The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

Investigation on Demodex infections among university students in Kunming City / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Demodex infection among students in Kunming Medical University, and identify the factors affecting Demodex infections, so as to provide the evidence for the development of the strategy for the prevention of Demodex infections. Methods A total of 1 463 students from Grade 2014 who studied Medical Parasitology in Kunming Medical University were included in the survey. Demodex was examined in students’facial skin using the cellophane tape method, and the species was identified using microscopy. The students’gender, ethnicity, place of origin and skin type were captured using a questionnaire survey. Results The overall prevalence of Demodex infections was 19.07% (279/1 463) on the facial skin among the university students, and a higher prevalence was seen in girls (21.16%, 183/865) than in boys (16.05%, 96/598) (χ2 =5.965,P <0.05).TheprevalenceofDemodex infectionswas18.33%(66/360)amongminorethnicstudents,andnoethnicity-specific prevalence was seen (P > 0.05). Demodex folliculorum was the predominant species, with a prevalence of 50.54% (141/279), and mild infections were predominant among all infections (96.77%, 270/279), without severe infections seen. Multivariate nonconditional logistic regression analysis revealed that gender and roommates with Demodex infections were risk factors of Demodex infections, and the infection was not associated with ethnicity, place of origin or skin type. There were only 2.53% (37/1 463) of the subjects understanding the knowledge pertaining to the prevention and control of Demodex infection. Conclusions A relatively low prevalence of Demodex infection is detected in the facial skin of students from Kunming Medical University, and Demodex infection is associated with gender and roommates with Demodex infections. Health education pertaining to the prevention of Demodex infections is suggested to be intensified among university students.

The prognostic value of baseline serum free light chain in immunoglobulin light-chain cardiac amyloidosis / 中华血液学杂志

Objective: To analyze the prognostic value of baseline serum free light chain (sFLC) in immunoglobulin light-chain cardiac amyloidosis (AL-CA) . Methods: Thirty patients diagnosed with AL-CA from January 2012 to December 2016 at Beijing Chaoyang Hospital were included in this study to retrospectively evaluate the clinical data. The cut-off value of dFLC (involved sFLC minus uninvolved sFLC) was determined according to the receiver operator characteristic curve (ROC) and grouped, the prognoses of both groups were evaluated. Results: The onset age of all AL-CA patients was 57 years old. It occurred more commonly in men (21 cases, 70%) and the light chains of immunoglobulin composed mainly of type λ (22 cases, 73.3%) . Renal involvements occurred in 17 cases (56.7%) . The median value of difference between involved and uninvolved serum immunoglobulin free light chain levels (dFLC) was 162.9 (57.9-401.6) mg/L. More subjects in the high dFLC group had higher BNP (P=0.005) , and shorter median survival than those in the low dFLC group (15 months vs 47 months, P<0.001) . Similar results of median survival were observed when the patients were redivided by a new cut-off value of 180 mg/L for dFLC (high dFLC group: 22 months, low dFLC group: 40 months, P=0.001) , or a κ/λ ratio in which patients with κ type sFLC-ratio<3.79 and λ type sFLC-ratio≥0.06 were grouped into the low sFLC-ratio (37 months) , and the reverse the high sFLC-ratio ones (25 months, P=0.021) . In multivariate analysis, dFLC and New York Heart Association (NYHA) classification of cardiac function were two risk factors associated with all-cause mortality in patients, of them the hazard ratio for higher dFLC was 12.13 (95%CI 2.98-49.30, P<0.001) . Conclusion: Measurement of the sFLC level could implicate the prognosis of AL-CA.

Strategy and progress of chemotherapy for cervical cancer / 中国实用妇科与产科杂志

As the treatment methods develop,the prognosis of cervical cancer has been significantly improved.Surgery and radiotherapy are still the main treatments for cervical cancer,accompanied by chemotherapy.For young patients with cervical cancer,radiotherapy can result in the ovarian failure and lead to a series of menopausal symptoms.Radiotherapy can also cause a lot of other complications and affect the quality of life.Chemotherapy,especially adjuvant chemotherapy before and after surgery,is drawing more and more attention recently.Therefore we made a summary of the latest progress in the strategies for postoperative adjuvant chemotherapy and preoperative neoadjuvant chemotherapy for cervical cancer.

Ligustrazine regulates LPS-induced apoptosis and inflammatory response of osteoarthritis chondrocytes via inhibiting phosphorylation of NF-κB P65 / 中国免疫学杂志

Objective: To explore the effect of ligustrazine on the LPS-induced apoptosis and inflammatory response of osteoarthritis chondrocytes. Methods: Osteoarthritis model was induced by LPS. Chondrocytes were divided into four group: control group, ligustrazine ( 20 μmol/L) group, LPS ( 100 ng/ml) group and ligustrazine ( 20 μmol/L) +LPS ( 100 ng/ml) group. Apoptosis was measured by Hoechst33258 staining. The levels of nitric oxide ( NO), tumor necrosis factor α ( TNF-α) and interleukin ( IL) -6 were detected by ELISA. The protein levels of collagenⅡ, aggrecan, matrix metalloproteinase 13 ( MMP-13), NF-κB P65 and p-NF-κB P65 were tested by Western blot. Results: The LPS-induced abnormal cell morphology and decreased number of cells were ameliorated by ligustrazine ( 20 μmol/L). The apoptosis in LPS group was higher than control group ( P＜0. 05). The LPS-induced enhancive apoptosis was reduced by ligustrazine ( P＜0. 05). Compared with control group, the expression of collagenⅡ and aggrecan was alleviated with increased expression of MMP-13 ( P＜0. 05). The LPS-induced declined expression of collagenⅡ and aggrecan and elevated expression of MMP-13 was inhibited by ligustrazine ( P＜0. 05). The levels of NO, TNF-α and IL-6 in LPS group were higher than control group ( P＜0. 05). The levels of NO, TNF-α and IL-6 in LPS+ligustrazine group were lower than LPS group ( P＜0. 05). Compared with control group, the rate of pP65/P65 in LPPS group was enhanced ( P＜ 0. 05). The LPS-indiced increased rate of p-P65/P65 was decreased by ligustrazine ( P ＜0. 05). Conclusion: Ligustrazine alleviates the LPS-induced apoptosis and inflammatory response of osteoarthritis chondrocytes via inhibiting phosphorylation of NF-κB P65.

Recent advances in the neural regulation of feeding behavior in adult Drosophila / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The ability to maintain metabolic homeostasis is a key capability critical for the survival and well-being of animals living in constantly changing environments. Metabolic homeostasis depends on neuromodulators, such as biogenic amines, neuropeptides, and hormones, to signal changes in animals' internal metabolic status and to orchestrate their behaviors accordingly. An important example is the regulation of feeding behavior by conserved molecular and cellular mechanisms across the animal kingdom. Its relatively simple brain coupled with well-characterized genetics and behavioral paradigms makes the fruit fly Drosophila melanogaster an excellent model for investigating the neuromodulatory regulation of feeding behavior. In this review we discuss the neuromodulators and neural circuits that integrate the internal physiological status with external sensory cues and modulate feeding behavior in adult fruit flies. Studies show that various specific aspects of feeding behavior are subjected to unique neuromodulatory regulation, which permits fruit flies to maintain metabolic homeostasis effectively.

Application of iASSIST-assisted total knee arthroplasty in the treatment of genu varum or genu valgus / 中国组织工程研究

BACKGROUND: Compared with conventional total knee arthroplasty (TKA), for patients with genu varum or genu valgus, indications, prosthesis choice, surgical accuracy and perioperative management during TKA should be paid more attention. OBJECTIVE: To compare the clinical effectiveness of iASSIST-assisted TKA and traditional TKA in the treatment of genu varum or genu valgus. METHODS: Twenty-one patients with genu varum or genu valgus undergoing TKA were selected, and were then randomized into two groups: iASSIST-assisted TKA (group A) or traditional TKA (group B). The surgical accuracy was compared between two groups by measuring the knee valgus angle of patients, and the angle between prosthesis components on the coronal and sagittal planes. Besides, the intraoperative blood loss, operation time, postoperative drainage, restored alignment, postoperative complications, hospitalization time, as well as Visual Analogue Scale and American Knee Society scores were recorded to assess the clinical effectiveness. RESULTS AND CONCLUSION: (1) The deviation of hip-knee-ankle angle, frontal femoral component angle, frontal tibial component angle, lateral femoral component angle and lateral femoral component angle in the two groups was less than 3°, and the group A exhibited better corrective efficacy. (2) The operation time in the group A was significantly longer than that in the group B; the hospitalization time in the group was significantly shorter than that in the group B; the restored alignment in the group A was significantly superior to that in the group B;the postoperative drainage, as well as Visual Analogue Scale and American Knee Society scores at 1 day and 1 week postoperatively in the group B were significantly superior to those in the group A (all P < 0.05). There were no significant differences in the intraoperative blood loss, incidence of complications, as well as Visual Analogue Scale and American Knee Society scores at postoperative 2 weeks and 1 and 3 months between two groups (P > 0.05). (3) These results manifest that for the patients with genu varum or genu valgus, both iASSIST-assisted TKA and traditional TKA can obtain satisfactory surgical accuracy, and the former has advantage in restricting the alignment of lower limbs. However, the long-term efficacy needs to be explored in depth.

Precision evaluatation of personalized knee osteotomy instrument based on 3D printing technology for the total knee arthroplasty / 局解手术学杂志

Objective To construct a personalized knee osteotomy instrument(POI)based on 3D printing technology for the total knee arthroplasty(TKA)and to evaluate the precision of POI.Methods The full-length CT scanning and MRI scanning of the affected lower limbs were performed before operation respectively.The data fusion of CT scanning and MRI scanning were performed with the 3D anatomical data,and then the articular cartilage were reconstructed.The force lines were measured with virtual personalized osteotomy,and TKA prosthe-sis installation were calculated by CAD software.Based on CAD mimic,the registration surface of POI for femoral condyle and tibial plateau were designed by Boolean Subraction calculation technique.The shape and limit structure(LS)of POI were designed according to the regis-tration surface and the osteotomy surface.Finally,POI were fabricated by FDM 3D printing technology.Femoral condylar POI and tibial plat-eau POI were manufactured 15 cases in each group.The difference between design and actual values(DDA)of POI and LS size were meas-ured with the DDA of DML calculated.And the deviation of the TKA prosthesis angle from the design value was measured to verify the precision of the osteotomy of POI.Results There was no significant difference in the shape of POI and LS between design and actual values(P>0.05). Moreover,there was no significant difference of DMLs(P>0.05).Meanwhile,there was no significant difference of TKA prosthesis angle be-tween the design and postoperative values(P>0.05).Conclusion 3D printing technique can accurately construct the POI of TKA.POI can accurately register the articular surface and guide the osteotomy in TKA,which is conducive to the precision of TKA operation.

Isolation and identification of exosomes derived from bone marrow mesenchymal stem cells / 基础医学与临床

Objective To develop a method of isolation and identification of exosomes of bone marrow mesenchymal stem cells.Methods The mesenchymal stem cells were cultured by whole bone marrow adherence method.A new reagent -exosomes extraction kit was used to isolate and collecte exosomes.The exosomes were identified by elec-tron microscopy,particle size detection,flow cytometry and Western blot.Results The expression of CD45 on the surface of the third generation bone marrow mesenchymal stem cells was negative,and CD73 and CD105 were posi-tive;exosomes derived from bone marrow mesenchymal stem cells were round or oval,the size is non-uniform,the diameter is 30~100 nm,have a complete membrane structure,and containing low-density substances;Particle size detection particle diameter of the main peak was 61.25 nm, in which the diameter of particles was about 20-200 nm accounted for 72.4%;exosome expressed CD63 and CD81;The expression of CD9 and CD63 from cell cul-ture supernatants was positive.Conclusions The exosomes can be collected in the medium of mesenchymal stem cells.The exosomes derived from bone marrow mesenchymal stem cells can be identified by electron microscopy, particle size detection,flow cytometry and Western blot.

Primary culture and identification of mouse renal proximal tubular epithelial cells / 生理学报

The present study was aimed to establish a modified method for culturing mouse renal proximal tubular epithelial cells (TECs). Renal cortex was isolated from mouse kidney and scissored into pieces. TECs were separated by digesting scissored renal cortex in type II collagenase combined with strainer filtration, and then cultured in DMEM. The morphology of TECs was observed under inverted microscopy. The cell proliferative ability was assessed by flow cytometry, and cell viability was analyzed by CCK-8 assay. The purity of TECs was identified by immunofluorescence. Immunofluorescence observation showed that more than 95% cells were epithelial marker CK18 positive and more than 90% cells expressed renal proximal TECs marker proteins, Villin, AQP1, and SGLT2. The cells could be subcultured for about 5 times. The cell proliferative ability declined following the repeated passage. This study introduced a modified efficient method for culturing highly purified mouse renal proximal TECs.

Accurate osteotomy assisted by individualized navigation templates for the treatment of children cubitus varus / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the feasibility and accuracy of a new navigation template for osteotomy in cubitus varus based on computer assistant design and 3D printing technology.</p><p><b>METHODS</b>The preoperative CT images of 15 children with cubitus varus from June 2015 to June 2016 were collected. According to the above data, the individual osteotomy navigate template match the distal humerus was designed by the software and printed by the 3D printer. Accurate osteotomy was performed with the assistant of the navigate template in the operation. Internal fixation of the osteotomy site was performed with 2 Kirschner wires. After surgery, a long arm plaster was applied with 20° of elbow flexion. All the patients underwent radiographic and clinical evaluations before surgery and at the follow-up examination.</p><p><b>RESULTS</b>During the operation, the navigate template with the individual design of 3D printing technology matched the bony markers of distal humerus. Accurate and simple osteotomy were performed along the resected surface of the navigation template. None of the cases required any kinds of revision surgery or had any complaint of cosmetic appearance. Average union time was 6.7 weeks(ranged, 6 to 8 weeks). Twelve patients got an excellent result and 2 got a good result according to the criteria described by Bellemore. There were no cases with complications of infection or ulnar nerve palsy or joint stiffness.</p><p><b>CONCLUSIONS</b>With the help of 3D printing technology, the accurate osteotomy in cubitus varus assisted by individualized navigate template can be realized. This technology can restore normal anatomical structure of the elbow joint to the greatest extent. It is worthy of popularization and application.</p>

Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus (HIV) infection epidemics.</p><p><b>METHODS</b>A prospective cohort study of newly registered patients in tuberculosis (TB) dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis.</p><p><b>RESULTS</b>Of 19,103 newly registered pulmonary TB patients, 925 (4.8%) were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322 (1.7%) deaths that occurred during TB treatment, 85 (26%) of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio (aOR) 7.86]. Other significant mortality risk factors included presentation with miliary TB (aOR 4.10; 95% confidence interval: 2.14-7.88), ⋝35 years of age (aOR 3.04), non-Han ethnicity (aOR 1.67), and farming as an occupation (aOR 1.59). For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death (aOR 5.48). A low CD4 count (⋜200 cells/µL) (aOR 3.27) at the time of TB treatment initiation and a lack of antiretroviral therapy (ART) administration (aOR 3.78) were also correlated with an increased risk of death.</p><p><b>CONCLUSION</b>Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.</p>

Glycemic Variation in Tumor Patients with Total Parenteral Nutrition / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN) are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients.</p><p><b>METHODS</b>This retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG) values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG.</p><p><b>RESULTS</b>The clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%), rectal carcinoma (17.3%), colon carcinoma (CC, 14.7%), gastric carcinoma (29.8%), pancreatic carcinoma (11.5%), and duodenal carcinoma (DC, 4.8%). The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time.</p><p><b>CONCLUSIONS</b>When tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG values. The ClinicalTrials.gov ID is NCT02024321.</p>

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers / 癌症

<p><b>INTRODUCTION</b>Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients.</p><p><b>METHODS</b>All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed.</p><p><b>RESULTS</b>HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months.</p><p><b>CONCLUSION</b>Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.</p>