Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Effects of extramedullary disease on patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.

Cloning and functional analysis of IPI gene from Fritillaria unibracteata Hsiao et K. C. Hsia / 药学学报

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

Application of whole-process management mode based on "Internet + nursing service" in the management of children with concealed penis / 中国实用护理杂志

Objective:To explore the effect of whole-process management mode based on "Internet + nursing service" in the management of children with concealed penis.Methods:This study adopted a quasi-experimental research method. A total of 383 children with concealed penis who were hospitalized in the Third Department of Urology of Hunan Provincial People′s Hospital from January 2018 to August 2021 were convenient selected. According to the sequence of admission, 195 children admitted from January 2018 to May 2020 were set as the control group, and 188 children admitted from June 2020 to August 2021 were set as the observation group. The control group was received conventional treatment and nursing, but the observation group was received whole-process management mode based on "Internet + nursing service". The length of hospitalization, incidence of complications after discharge, anxiety of the children′s parents and satisfaction of the doctors, the specialist & nurse sharing and the children′s parents were compared between the two groups.Results:Finally, 186 and 193 children were included in the observation group and the control group, respectively After the intervention, in the observation group, the length of hospitalization, anxiety score of the children′s parents, difference of anxiety score of the children′s parents, satisfaction content of the doctors, satisfaction effect of the doctors, satisfaction content of the specialist & nurse sharing, satisfaction effect of the specialist & nurse sharing, satisfaction content of the children′s parents and satisfaction effect of the children′s parents were (4.30 ± 1.35) d, (35.08 ± 3.17) points, (19.14 ± 4.35) points,(4.57 ± 0.54) points, (4.71 ± 0.49) points, (4.75 ± 0.50) points, (5.00 ± 0.00) points, (4.60 ± 0.49) points, (4.65 ± 0.49) points; in the control group, the scores were (5.50 ± 1.41) d, (44.79 ± 3.30) points, (9.22 ± 3.67) points, (3.71 ± 0.49) points, (4.00 ± 0.58) points, (3.50 ± 0.58) points, (3.25 ± 0.50) points, (3.54 ± 0.59) points, (3.64 ± 0.67) points. The differences between the two groups were statistically significant ( t values were -23.94-29.19, all P<0.05). The complication rates of the observation group and the control group were not statistically significant ( χ2=0.64, P>0.05). Conclusions:The whole-process management mode based on "Internet + nursing service" is beneficial to shorten the length of hospitalization, relieve the degree to anxiety of the children′s parents, improve the satisfaction of the doctors, the specialist & nurse sharing and the children′s parents, and accelerate the rehabilitation of children, which is worthy of clinical promotion.

Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and β-catenin / 中国针灸

OBJECTIVES@#To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients.@*METHODS@#Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups.@*RESULTS@#Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group.@*CONCLUSIONS@#In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.

Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

How adverse and benevolent childhood experiences influence depression and suicidal ideation in Chinese undergraduates: a latent class analysis

BACKGROUND@#There has been minimal research on the role of benevolent childhood experiences (BCEs) and how such events may offer protection from the insidious effects of adverse childhood experiences (ACEs) or later in life.@*OBJECTIVES@#This research aims to learn how BCEs and ACEs interact to affect adolescents' psychological distress.@*METHODS@#Cross-sectional survey was conducted in three cities (Xuzhou, Nanjing, and Wuhan) in China from March 2021 to May 2021. Latent class analysis (LCA) was used to classify the patterns of ACEs and BCEs. We adopted hierarchical multivariable regression to examine the influences of ACEs and BCEs on depression and suicidal ideation.@*RESULTS@#To explore the relationship between childhood experience and suicidal ideation and depression, LCA revealed three patterns of ACEs: (1) emotional abuse (10.57%); (2) high ACEs (0.55%); and (3) low ACEs classes (88.88%). Adolescents with emotional abuse (depression: OR = 3.82, 95%CI = 2.80-5.22, P < 0.001; suicidal ideation: OR = 5.766, 95%CI = 3.97-8.38, P < 0.001) and high ACEs class (suicidal ideation: OR = 5.93, 95%CI = 1.19-29.66, P < 0.05) had an increased risk of psychological distress (reference: low ACEs). LCA revealed four patterns of BCEs: (1) relationship support (14.54%); (2) low BCEs (4.85%); (3) high BCEs (55.34%); and (4) high quality of life classes (25.28%). Adolescents with a high quality of life (depression: OR = 0.09, 95%CI = 0.05-0.16, P < 0.001; suicidal ideation: OR = 0.22, 95%CI = 0.12-0.40, P < 0.001) and high BCEs (depression: OR = 0.05, 95%CI = 0.03-0.09, P < 0.001; suicidal ideation: OR = 0.15, 95%CI = 0.09-0.26, P < 0.001) protected the mental health of adolescents (reference: low BCEs).@*CONCLUSIONS@#High ACEs and emotional abuse classes were significantly associated with poorer mental health symptoms, including suicidal ideation and depression. In contrast, high BCEs and high quality of life classes were associated with better mental health. These findings point out that it is more necessary to identify and support victims of ACEs, and it is urgent to increase BCEs in early childhood.

Comparison of the long-term outcomes of focused ultrasound ablation surgery for uterine fibroids and myomectomy / 中华妇产科杂志

Objective:To compare the long-term outcomes after focused ultrasound ablation surgery (FUAS) versus myomectomy for uterine fibroids.Methods:A retrospective study was conducted on women who were treated by FUAS or myomectomy for uterine fibroids at First Medical Center of Chinese PLA General Hospital from January 2007 to January 2015. Regular follow-up was conducted to evaluate the symptoms relief, symptoms recurrence, the need for re-interventions and complications of the two groups.Results:The effective rates were 95.7% (730/763) and 95.5% (1 151/1 205) in women who were treated by FUAS and myomectomy, no statistical difference was seen between the two groups ( χ2 =0.027, P=0.869). The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in FUAS group were 1.8%, 6.8%, 11.9%, 15.2% and 15.9%, respectively; and the cumulative re-intervention rates were 0.7%, 4.1%, 6.8%, 9.9% and 11.0%, respectively. The cumulative rates of symptoms recurrence at 1 year, 3 years, 5 years, 8 years and 10 years of follow-up in myomectomy group were 1.8%, 5.9%, 10.6%, 14.2% and 14.9%, respectively; and the cumulative re-intervention rates were 0.9%, 4.5%, 7.8%, 10.3% and 11.4%, respectively. No statistical differences were seen between the two groups (all P>0.05). There were no significant differences in the effective rate, symptoms recurrence rate and re-intervention rate between the two groups in patients with intermural fibroids; but the effective rate of FUAS (95.9%, 235/245) was higher than that of myomectomy (89.1%, 115/129), the symptoms recurrence rate (11.9%, 28/235) was lower than that of myomectomy (27.8%, 32/115), and the re-intervention rate (7.7%, 18/235) was lower than that of myomectomy (17.4%, 20/115) in patients with submucosal fibroids, there were significant different (all P<0.05). The effective rate of FUAS (91.0%, 132/145) was lower than that of myomectomy (97.0%, 322/332), the symptoms recurrence rate (32.6%, 43/132) was higher than that of myomectomy (9.9%, 32/322), and the re-intervention rate (22.0%, 29/132) was higher than that of myomectomy group (6.2%, 20/132) in patients with subserosal fibroids, there were significant different (all P<0.01). The incidences of total [1.8% (14/763) vs 21.9% (264/1 205)], minor and moderate adverse events were lower in FUAS group than myomectomy group (all P<0.001). Conclusion:Satisfaction with long-term outcomes after FUAS treatment or myomectomy for uterine fibroids is comparable.

Expression profile and clinical significance of miRNA in children with autism spectrum disorder / 中国医师杂志

Objective:The purpose of this study was to analyze the expression profile of miRNAs in children with autism spectrum disorders (ASD), and to discuss the clinical significance of differentially expressed miRNAs.Methods:MiRNA microarray was used to analyze the expression of miRNA in peripheral blood of 3 pairs of ASD patients-healthy controls; 17 pairs of ASD patients-healthy controls were used to verify the differentially expressed miRNA; Receiver operating characteristic (ROC) curve was used to analyze the differential expression the value of miRNA in the diagnosis of ASD.Results:A total of 32 differentially expressed genes were screened by 3 pairs of miRNA microarray including 12 up-regulated miRNAs and 20 down-regulated miRNAs. miRNA verification of 20 differentially expressed miRNAs showed miR-15a-5p, miR-27a-3p , miR-142-3p and miR-142-5p were significantly down-regulated in children with ASD, with statistically significant difference (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) of the above four miRNAs diagnosing ASD were all greater than 0.70, with sensitivities 94.12%, 100%, 100%, and 82.35%, respectively. Conclusions:The expression of miR-142-3p, miR-27a-3p/miR-15a-5p, and miR-142-5p is down-regulated in the peripheral blood of ASD patients, and has the potential as biomarkers for early screening of ASD.

Effect of hierarchical and phased teaching method on the teaching of neurosurgery interns / 中华医学教育探索杂志

Objective:To explore the teaching effect of hierarchical and phased teaching method on the teaching of neurosurgery interns.Methods:Thirty-five interns of the Department of Neurosurgery of The First People's Hospital of Liangshan Yi Autonomous Prefecture from July 2019 to March 2020 were selected as the control group, and received the traditional clinical teaching method. Another 34 interns from June 2020 to February 2021 were selected as the research group, and adopted the hierarchical and phased teaching method. The graduation examination results were compared, and the scores of mini-clinical evaluation exercise (Mini-CEX) scale before and after practice and the recognition of teaching methods by interns were compared. SPSS 24.0 was used for t test and chi-square test. Results:The results of theoretical knowledge of neurosurgery [(90.15±4.47) points], operation skills [(91.12±3.68) points] and clinical case analysis ability [(87.32±5.41) points] in the study group were higher than those in the control group [(85.26±5.19) points, (86.14±5.25) points and (80.94±4.26) points], and the differences were statistically significant ( P<0.001). The scores of Mini-CEX scale in the two groups after internship were both higher than those before internship ( P<0.001), which in the study group after internship were higher than those in the control group ( P<0.001). The recognition of the teaching method in improving the learning interest and enthusiasm, strengthening the ability to master knowledge, improving the ability to analyze and deal with clinical problems, improving the ability to combine theoretical knowledge with practice and improving the clinical thinking ability of interns in the study group were higher than those in the control group ( P<0.05). Conclusion:In the clinical teaching of neurosurgery interns, the application of hierarchical and phased teaching method can significantly improve the comprehensive assessment ability and professional quality of interns, and can also improve their recognition of this teaching method.

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Application value of imaging examination in the diagnosis of Muller-Weiss disease / 中国骨伤

OBJECTIVE@#To analyze radiological characteristics of Muller-Weiss disease, evaluate the clinical value of the imaging examination in diagnosis of Muller-Weiss disease.@*METHODS@#The imaging data of 26 patients with Muller-Weiss disease were collected from September 2015 to August 2020, including 7 males and 19 females, aged 43 to 68 years old with an average of (52.7±4.6) years old. In the X-ray examination observed the shape and position of the navicular bone. The talar-first metatarsal angle(TFM) was measured on the weight-bearing anteroposterior radiograph. The arch angle and angle between mid-axis of talus and mid-axis of the first metatarsal(Meary angle) were measured on the weight-bearing lateral radiographs. The morphology, density, adjacent joint space and position of the navicular bone were evaluated by computed tomography(CT), and magnetic resonance imaging(MRI) was used to observe the shape, signal, cartilage and surrounding soft tissue changes of the navicular bone.@*RESULTS@#Among 26 patients, 21 cases were unilateral and 5 cases were bilateral;X-ray examination showed that the lateral part of navicular bone of foot was compressed and flattened, showing"comma like"or"drop like", navicular moved to the medial side, partial fragmentation of bone, peripheral articular hyperplasia, uneven density and narrowing of relationship gap. According to Meary angle and deformity degree of the affected foot on the lateral X-ray of the load-bearing foot, Maceira staging was performed. There were 0 cases in stageⅠ, 2 cases in stage Ⅱ, 11 cases in stage Ⅲ, 9 cases in stage Ⅳand 4 cases in stage Ⅴ. CT examination showed bone fragmentation, medial displacement of navicular bone and formation of the talocalcaneal joint. MRI examination showed the irregular shape and uneven signal of navicular bone, narrowing of joint space, talocalcaneal joint surface hyperplasia and cartilage destruction, tarsal joint effusion and swelling of surrounding soft tissue.@*CONCLUSION@#Muller-Weiss disease has specific imaging manifestation, and an accurate diagnosis can be made based on the patient's age, gender, and clinincal history. Preoperative imaging examination can stage the disease, help clinicians to formulate better surgical plans, and postoperative imaging examination can better evaluate the surgical effect.

Comparison between Ultrasonography and CT in Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ2=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ 2=82.26,P<0.001;χ2=114.01,P<0.001;χ2=82.26,P<0.001) and accuracy (χ2=20.27,P<0.001;χ2=15.56,P<0.001;χ2=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ2=17.01,P<0.001;χ2=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.

Experimental study on the correlation between microcirculation and contrast-enhanced ultrasonography after crush injury of limbs / 中华超声影像学杂志

Objective:To explore the microcirculation formation mechanism of contrast-enhanced ultrasonography imaging performance in rabbits with limb muscle crush injury.Methods:Seventy-two New Zealand white rabbits were randomly divided into two groups. A limb muscle crush injury model was created by airing a balloon cuff device with a force of 40 kPa. Contrast-enhanced ultrasonography parameters were detected in the first group.In vivo microcirculation parameters were detected in the second group. Fine blood vessel diameter and blood flow velocity were calculated before extrusion and 0.5 h, 2 h, 6 h, 24 h, and 3 days after decompression.Results:Totally six animals died before the end of the experiment (3 rabbits in ultrasonic imaging and microcirculation detection groups, respectively). Compared with the uninjured muscle, the reperfusion of the injured muscle showed early and high enhancement in contrast-enhanced ultrasonography images. The peak intensity and area under the curve were significantly higher than those of the control subgroup at each time point after decompression(all P<0.05), and reached the peak at 24 h after decompression. The time-intensity curve showed a trend of rapid elevation and gradual drop. In the microcirculation group, compared with the control group, fine artery and vein diameters in the experimental group were wider and the blood flow velocity was slower, especially in the fine veins(all P<0.05). At each time point after decompression, there was a statistical difference between the control subgroup and the control subgroup, and the change reached the peak at 24 h after decompression. The blood flow state showed that the arterioles were dominated by linear flow and linear grain flow at each time point after decompression, and linear grain flow, grain flow and grain pendulum flow were observed in the fine veins. Blood flow stagnation and adhesion of white blood cells and white microthrombus were also observed in the fine veins. Correlation analysis showed that the peak intensity and area under the curve were positively correlated with the inner diameter of arterioles and veins( r=0.84, 0.94; r=0.85, 0.94; all P<0.05), and negatively correlated with the flow velocity of arterioles and veins( r=-0.94, -0.96; r=-0.93, -0.96; all P<0.05). Conclusions:In vivo microcirculation detection can reflect changes in muscle microvascular diameter and blood flow velocity, which have a correlation with quantitative ultrasound imaging parameters.

Elimination of hepatitis B virus infection in children: experience and challenge in China / 中华医学杂志(英文版)

Chronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to 2 × 105 U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.

Research progress of robotic bronchoscopy system and prospect of the combination with artificial intelligence / 中国胸心血管外科临床杂志

@#The robotic bronchoscopy system is a new technology for lung lesion location, biopsy and interventional therapy. Its safety and effectiveness have been clinically proven. Based on many advanced technologies carried by the robotic bronchoscopy system, it is more intelligent, convenient and stable when clinicians perform bronchoscopy operations. It has higher accuracy and diagnostic rates, and less complications than bronchoscopy with the assistance of magnetic navigation and ordinary bronchoscopy. This article gave a review of the progress of robotic bronchoscopy systems, and a prospect of the combination with artificial intelligence.

Role of IL-6/STAT3 signaling pathway in high-risk human papillomavirus associated cervical cancer cells / 中国医师杂志

Objective:To investigate the role and mechanism of interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway in proliferation, invasion and apoptosis of cervical cancer cells infected by high-risk human papillomavirus (HPV).Methods:HPV-18 positive HeLa cells cultured in vitro were divided into control group (normal cultured), IL-6 group (stimulated with 50 ng/ml IL-6 for 24 h) and IL-6 + AG490 group (stimulated with 50 ng/ml IL-6 and 100 μmol/L STAT3 signaling pathway inhibitor AG490 for 24 h). Methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell survival rate. The ability of cell clone formation was detected by plate clone formation assay. The cell invasion was detected by transwell chamber assay. The cell apoptosis was detected by flow cytometry. Western blot was used to detect the protein expression levels of STAT3, phosphorylation of (p)-STAT3, B-cell lymphoma-2 gene (Bcl-2), CyclinD1 and matrix metalloproteinase-9 (MMP-9). Results:Compared with those in the control group, the cell survival rate, clone formation rate, number of invasive cells and the protein expression levels of p-STAT3, Bcl-2, CyclinD1 and MMP-9 in IL-6 group were significantly higher, while the apoptosis rate was significantly lower ( P<0.05); at the same time, compared with those in IL-6 group, the cell survival rate, clone formation rate, the number of invasive cells and the protein expression levels of p-STAT3, Bcl-2, CyclinD1 and MMP-9 in IL-6 + AG490 group were significantly lower, while the apoptosis rate was significantly higher ( P<0.05). Conclusions:IL-6/STAT3 signaling pathway plays an important role in the malignant progression of high-risk HPV infected cervical cancer cells, and its mechanism may be related to the up-regulation of CyclinD1, MMP-9, Bcl-2 protein expressions.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Value of Contrast-enhanced Ultrasound Parameters in Evaluating K-W Nodule Formation in Diabetic Nephropathy / 中国医学科学院学报

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(

Research progress in biosynthesis of podophyllotoxin and its derivatives / 生物工程学报

Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and Sinopodophyllum hexandrum. Etoposide and teniposide are produced semisynthetically from PTOX and used clinically to treat several forms of cancer. As a typical representative of new drug discovery from natural products, the production of PTOX solely depends on extraction from plants, resulting in severe contradiction between supply and demand. With the advantages of unconstrained resources and eco-friendly reaction conditions, biosynthesis method has become a trend in the production of PTOX and its derivatives. In this review, we summarize the research progress of PTOX biosynthesis in plants and expound the functions of the key enzymes as well as their subcellular location. The synthetic biology for production of PTOX intermediates in a tobacco chassis is also introduced. Finally, the heterologous expression and biotransformation of PTOX in microorganisms is summarized, which sets the foundation for the efficient microbial production of PTOX using cell factories.