Survival benefits of para-aortic lymphadenectomy in colorectal cancer with clinically suspected para-aortic lymph node metastasis: a meta-analysis and systematic review.

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.

Application of immune checkpoint inhibitors in immunotherapy for gastric cancer.

Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.

In recent years, with the application of immunotherapy, clinical efficacy in gastric cancer has been effectively improved. At present, it is encouraging that immunotherapy combined with chemotherapy has become the first choice for the treatment of patients with advanced gastric cancer. However, researchers remain committed to exploring the efficacy of immunotherapy in combination with various therapies. Equally important, the identification of biomarkers can facilitate the selection of patients suitable for immunotherapy. This article summarizes important immunotherapy clinical trials and discusses therapeutic combinations and biomarkers being explored.

Contactless multiscale measurement of cardiac motion using biomedical radar sensor.

Introduction: A contactless multiscale cardiac motion measurement method is proposed using impulse radio ultra-wideband (IR-UWB) radar at a center frequency of 7.29 GHz. Motivation: Electrocardiograph (ECG), heart sound, and ultrasound are traditional state-of-the-art heartbeat signal measurement methods. These methods suffer from defects in contact and the existence of a blind information segment during the cardiogram measurement. Methods: Experiments and analyses were conducted using coarse-to-fine scale. Anteroposterior and along-the-arc measurements were taken from five healthy male subjects (aged 25-43) when lying down or prone. In every measurement, 10 seconds of breath-holding data were recorded with a radar 55 cm away from the body surface, while the ECG was monitored simultaneously as a reference. Results: Cardiac motion detection from the front was superior to that from the back in amplitude. In terms of radar detection angles, the best cardiac motion information was observed at a detection angle of 120°. Finally, in terms of cardiac motion cycles, all the ECG information, as well as short segments of cardiac motion details named blind ECGs segments, were detected. Significance: A contactless and multiscale cardiac motion detection method is proposed with no blind detection of segments during the entire cardiac cycle. This paves the way for a potentially significant method of fast and accurate cardiac disease assessment and diagnosis that exhibits promising application prospects in contactless online cardiac monitoring and in-home healthcare.

The Expression of PPAR Pathway-Related Genes Can Better Predict the Prognosis of Patients with Colon Adenocarcinoma.

The postoperative survival time and quality of life of patients with colon adenocarcinoma (COAD) varies widely. In order to make accurate decisions after surgery, clinicians need to distinguish patients with different prognostic trends. However, we still lack effective methods to predict the prognosis of COAD patients. Accumulated evidences indicated that the inhibition of peroxisome proliferator-activated receptors (PPARs) and a portion of their target genes were associated with the development of COAD. Our study found that the expression of several PPAR pathway-related genes were linked to the prognosis of COAD patients. Therefore, we developed a scoring system (named PPAR-Riskscore) that can predict patients' outcomes. PPAR-Riskscore was constructed by univariate Cox regression based on the expression of 4 genes (NR1D1, ILK, TNFRSF1A, and REN) in tumor tissues. Compared to typical TNM grading systems, PPAR-Riskscore has better predictive accuracy and sensitivity. The reliability of the system was tested on six external validation datasets. Furthermore, PPAR-Riskscore was able to evaluate the immune cell infiltration and chemotherapy sensitivity of each tumor sample. We also combined PPAR-Riskscore and clinical features to create a nomogram with greater clinical utility. The nomogram can help clinicians make precise treatment decisions regarding the possible long-term survival of patients after surgery.

Key Signaling Events for Committing Mouse Pluripotent Stem Cells to the Germline Fate.

The process of germline development carries genetic information and preparatory totipotency across generations. The last decade has witnessed remarkable successes in the generation of germline cells from mouse pluripotent stem cells, especially induced germline cells with the capacity for producing viable offspring, suggesting clinical applications of induced germline cells in humans. However, to date, the culture systems for germline induction with accurate sex-specific meiosis and epigenetic reprogramming have not been well-established. In this study, we primarily focus on the mouse model to discuss key signaling events for germline induction. We review mechanisms of competent regulators on primordial germ cell induction and discuss current achievements and difficulties in inducing sex-specific germline development. Furthermore, we review the developmental identities of mouse embryonic stem cells and epiblast stem cells under certain defined culture conditions as it relates to the differentiation process of becoming germline cells.

Morphological characterization of adult mouse Leydig cells in culture.

The morphology and function of Leydig cells are changed during the development, mature and senility of Leydig cells along the life span of males. This study was to observe the growth morphology of adult mouse Leydig cells in culture, aiming to provide a reference for furthermore understanding of the biological function of Leydig cells by in vitro model. Testes of two-month-old mice were decapsulated and then the Leydig cells were isolated by collagenase digestion and were cultured in DMEM/F12 supplemented with 10% FBS. The Leydig cells were identified by HSD3B staining and RT-PCR. After 48-h Leydig cell culture, both the nucleus and the cytoplasm were very clear under the optical microscope. The nucleus was big and round and the cytoplasm was filled with abundant lipid drops with a strong refractivity. After 5-day culture, Leydig cells were fully elongated in spindle, triangular, polygonal, oval or irregular shapes. Some cells grew in aggregation, and some cells grew independently. Leydig cells in aggregation elongated many cellular tentacles for intercellular connections, which formed an epithelium-like appearance. After HSD3B staining, the individual Leydig cells were stained with different extents, demonstrated that the heterogeneity of HSD3B activity in individual Leydig cells in primary culture. RT-PCR results showed that Leydig cells in culture after 5 days could express Leydig cell-specific transcriptions, HSD3B6, CYP17A1 and StAR. These results showed the morphological characterization of adult mouse Leydig cells in culture, which will lay a foundation to elucidate the relationship between the morphology and function of Leydig cells.

Effects of low molecular weight heparin on clot rate and activated clotting time: an in vitro study.

BACKGROUND: Due to lack of point-of-care testing, the use of low-molecular-weight heparin (LMWH) therapy in some special patients is restricted. This study was designed to explore the effects of LMWH on clot rate (CR) and activated clotting time (ACT), and to search for an appropriate method for bedside monitoring of anticoagulant activity of LMWH. METHODS: Thirty-two healthy volunteers were selected from the staff of Beijing Tongren Hospital. CR and ACT were measured with different reagents (glass beads, diatomite, kaolin and magnetic bar) on blood samples spiked with increasing concentrations of LMWH (dalteparin, 0.2-1.8 IU/ml). Correlations between concentrations of LMWH and values of CR and ACT were analysed based on the data obtained and regression analysis was performed to establish a regression equation. RESULTS: With the increase in doses of dalteparin, CR values reduced gradually. The values of CR of four reagents (glass beads, diatomite, kaolin and magnetic bar) were 20.4-4.5 IU/min, 27.4-6.9 IU/min, 27.5-7.9 IU/min and 7.8-0.1 IU/min respectively and an linear relationship was observed between the CR values and dalteparin concentrations (P < 0.05). The values of ACT were 173-615 seconds, 130-270 seconds, 123-226 seconds, 337-1411 seconds respectively, which showed a linear regression between the ACT values and dalteparin concentrations (P < 0.01). Differences in slope of the regression curves of ACT were observed with all the reagents tested (glass beads 248.2 s/IU, diatomite 74.8 s/IU, kaolin 58.2 s/IU and magnetic bar 1112.2 s/IU, P < 0.01). While the minimum concentration of dalteparin was 0.2 IU/ml, 0.4 IU/ml, 1.4 IU/ml and 0.2 IU/ml separately, the ACT values of the four coagulants (glass beads, diatomite, kaolin and magnetic bar) were beyond the normal limit and showed a noticeable increase respectively (P < 0.01). CONCLUSIONS: This study showed that there was an excellent linear relationship between the CR and ACT values and dalteparin concentrations for all the four reagents (glass beads, diatomite, kaolin and magnetic bar) in vitro. The sensitivity of different coagulation reagents to LMWH different. Choosing a suitable reagent, both CR and ACT were possible to be used as a convenient bedside test for LMWH.

[Progress in exploring genes for high fertility in ewes].

Fecundity trait in sheep is regulated by some major genes. Among them, BMPR-IB, BMP-15, and GDF-9 are most distinguishing. The mutant FecB of BMPR-IB has multiplicative effects on ovulation. GDF-9's mutants FecGH, FecI, and BMP-15's mutants FecXI, FecXH, FecXG, FecXB, FecXL, and FecXR increase ovulation rate in the heterozygote but result in sterile phenotypes in the homozygote, while GDF-9's mutant, FecGE, only increases ovulation rate in the homozygote. In addition, Woodlands and Lacaune are known as inheritable major genes. Woodlands gene is an X-linked maternally imprinted gene, and Lacaune is similar to FecB with a multiplicative effect on ovulation rate. The size of the effect of one copy of a mutation on ovulation rate ranges from an extra 0.4 ovulations for the woodlands mutation to an extra 1.5 ovulations for the BMPR-IB and Lacaune mutation. Investigation into these genes will not only help to select breeds with high fertility, but also give a chance to further elucidate the mechanism involved in the phenomenon. This review summaries the source, location, phenotype, and mechanism of the major genes in all breeds of sheep.

[Sensitivity of new reagents for laboratory monitoring of low molecular weight heparin: an in vitro study].

OBJECTIVE: To explore the sensitivity of new activated clotting time (ACT) reagent for laboratory monitoring of low molecular weight heparin (LMWH). METHODS: Blood samples were collected from 30 healthy volunteers and different doses of LMWH (dalteparin) added. The dalteparin concentration of final blood samples was 0.1 - 1.8 U/ml. ACT and clot rate (CR) were measured with traditional reagent kaolin and new reagent magbar. Linear regression analysis was performed and a regression equation established between different dalteparin concentrations and their corresponding ACT and CR values. RESULTS: With rising dalteparin concentrations, the ACT values became gradually extended and the CR values were gradually reduced by both kaolin and magbar. Analysis of dose-response curves was obtained in vitro. And an excellent linear relationship was observed between the ACT and dalteparin concentrations for two reagents (P < 0.01). An exponential relationship was observed between the CR and dalteparin concentrations (P < 0.01). Differences in slope of regression curves of ACT were observed with the tested reagents (magbar 1097.6 s/U vs kaolin 59.3 s/U, P < 0.01). CONCLUSION: This in vitro study has shown that the sensitivity of new ACT test reagent (magbar) is good for laboratory monitoring of dalteparin. The new reagent magbar may be used for bedside monitoring of anticoagulant activity of LMWH.

In vitro anticoagulation monitoring of low-molecular-weight heparin.

BACKGROUND: Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time. METHODS: A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. RESULTS: The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant. CONCLUSIONS: The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-IIa activities.

[Expression of TGFbeta1 and its type I receptors ALK1 and ALK5 mRNA in brain arteriovenous malformation].

OBJECTIVE: To explore the expression of transforming growth factor beta1 (TGFbeta1) and its type I receptors activin-like kinase 1 (ALK1) and ALK5 mRNA in the development of brain arteriovenous malformation (BAVM). METHODS: The mRNA expressions of TGFbeta1, ALK1and ALK5 were detected with semiquantitative RT-PCR in patients with BAVM. RESULTS: The expressions of TGFbeta1 and ALK5 mRNA increased significantly in BAVM, and their relative expression quantity were 0.777-/+0.047 and 0.585-/+0.074, respectively. However, ALK1 mRNA expression declined significantlies with a relative expression of 0.173-/+0.044 in comparison with the control group (0.720-/+0.098, P<0.01). CONCLUSION: The balance of TGFbeta1 and its type I receptors ALK1 and ALK5 mRNA expressions may play important role in the development of BAVM.

[Two incompatible plasmids coexpress the human endostatin and predigested human plasminogen kringle 5 in E. coli].

OBJECTIVE: To construct the recombinant plasmid pET28a/hES and coexpress the human endostatin (hES) and predigested human plasminogen kringle 5 (predhPK-5) in E. coli. METHODS: The mRNA was extracted from human liver tissue, and the endostatin gene was amplified by RT-PCR, which then was cloned into pET-28a(+). Under screening pressure by ampicillin and kanamycin simultaneously, E. coli BL21 (DE3) was cotransformed with pET28a/hES and pGEX-1lambdaT/predhPK-5 and induced with IPTG to express the recombinant proteins. The stability of cotransformants existing in E. coli was measured through two aspects in the serial culture time and passage number of bacterium. RESULTS: The two incompatible plasmids could be coexisted under the pressure of two antibiotics (ampicillin and kanamycin). After induced with IPTG, both human endostation and predhPK-5 gene were coexpressed, and the recombinant proteins comprised about 20% and 21% of total cell proteins, respectively. The two incompatible plasmids could still be maintained in over 75% E. coli cells for at least 16 hours or after 120 passages under the pressure of two antibiotics. CONCLUSION: The two incompatible plasmids pET28a/hES and pGEX-1lambda T/predhPK-5 may coexpress the recombinant proteins in E. coli. A new method for coexpression of proteins in E. coli containing two incompatible plasmids is proved to be feasible.

[One-stage operation of ventriculo-peritoneal shunt and cranioplasty: analysis of 54 cases].

OBJECTIVE: To study the application of one-stage operation of ventriculo-peritoneal shunt and cranioplasty for hydrocephalus complicated by skull defect. METHOD: The clinical records of 54 patients with hydrocephalus complicated by skull defect treated with one-stage operation of ventriculo-peritoneal shunt and cranioplasty were reviewed in comparison with those of 30 patients receiving two-stage operations. RESULT: The clinical outcome of the patients receiving the two surgical procedures did not differ significantly, but two patients undergoing one-stage operation required replacement of the shunt pump due to elevation of intracranial pressure. Implementation of one-stage operations shortened the length of hospital stay and reduced the expense of patients. CONCLUSION: Hydrocephalus in combination with skull defect can be treated generally with one-stage operations and care must be taken in choosing adequate shunt tube according to the intracranial pressure measured preoperatively.

Study on a non-contact life parameter detection system using millimeter wave.

OBJECTIVE: To study the basic principle and design method of a non-contact life detection system using 36 GHz millimeter wave. METHOD: Continuous wave radar techniques and signal processing techniques including zero intermediate frequency, frequency domain accumulation and adaptive noise cancellation were used in the system. RESULT: When the radiated power was about a milliwatt (mW) and detection range was up to 3 meters, the experimental results showed that this system can well detect the heartbeat and respiration signals from human subjects through common clothes and quilts. CONCLUSION: The system is feasible and effective due to its high detection sensitivity, small antenna, simple structure, easy miniaturization and safety to the human subject. It can be used for long-term continuous monitoring, especially suitable for the astronauts.

[Development of an analysis system for X-ray cephalometry by Windows platform].

Here in this paper introduced is an analysis system for X-ray cephalometry developed through Windows platform,which includes three parts: data input, cephalometry analysis & calculation, and display & printing of diagnostic results. It has been applied in orthodontic department of Stomatological Hospital of the Fourth Military Medical University, and it is quite convenient for doctors' cephalometry diagnosis.

[Research on the hyperthermia-therapy performances of invasive microwave antennas].

The paper introduces four kinds of 2450 MHz antennas including noninsulted (bare), insulated-open-tip (I.O.T.), dipole-type and sleeve invasive microwave ones. The comparison between the antennas' hyperthermia performances in the muscle tissue phantom made by specific absorption rate (SAR) shows that the sleeve antenna is the best. It has a bigger heating range and a changeless shape and is independent of the inserting depth.