[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Correlation analysis of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and central cervical lymph node metastasis of papillary thyroid microcarcinoma].

Objective: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and central lymph node metastasis (CLNM) in patients with cN0 papillary thyroid microcarcinoma (PTMC). Methods: The clinicopathological data of PTMC patients confirmed by surgery and pathology in the 81st Military Hospital of People's Liberation Army from 2016 to 2019 were collected, and the relationship between preoperative NLR, PLR levels and postoperative PTMC CLNM were analyzed. Logistic regression analysis was used for multivariate analysis. Receiver operating characteristic (ROC) curve was used to determine the cutoff value of NLR and PLR. The interaction relative excess risk was used to analyze the relationship between NLR, PLR and CLNM. Results: Among 220 patients with cN0 stage PTMC, 92 were CLNM. The ROC curve showed that when the cutoff value of NLR was 2.5 and the cutoff value of PLR was 175, the highest Youden index was 0.318 and 0.264, respectively. NLR and PLR were both related to CLNM (P<0.05). The tumor long diameter, multifocality, NLR≥2.5 and PLR≥175 were independent impact factors of CLNM (P<0.05). The results of the interaction showed that the relative excess risk of the interaction was 5.531 (95%CI: 0.160, 10.901, P=0.016), the attribution ratio was 0.512 (95%CI: 0.230, 0.794, P=0.009), and the synergy index was 2.294 (95%CI: 1.492, 4.579, P=0.022), suggested that NLR and PLR had an interactive effect, and these two synergistically promoted CLNM. Conclusions: NLR and PLR are independent risk factors for cN0 stage PTMC CLNM. When NLR≥2.5 and PLR≥175, preventive central lymph node dissection should be routinely performed.

Characterization of bacterial microbiota diversity in Tibetan pigs fed with green forage in Linzhi of the Tibet autonomous region.

The acute shortage of forage resources is a serious problem for Tibetan pigs in the Tibet region, and the composition of feed can change the structure of the intestinal flora. This study first reported the effect of Alfalfa and Chenopodium glaucum feeding on the microbial diversity in Tibetan pigs, contributing to the forage exploitation of Tibetan pigs in the Tibet region.

[A study of bacterial distribution and drug resistance in skin and soft tissue infection].

Objective: To investigate pathogenic bacteria and drug resistance in the patients with skin and soft tissue infection in order to provide the scientific evidences for clinical reasonable use of antibiotics. Methods: A retrospective analysis was performed on patients with skin and soft tissue infections in Department of Dermatology, Peking University Third Hospital from January 2012 to December 2017. Pus, secretions, skin lesions, urine, throat swabs, and alveolar lavage fluid were collected for bacterial culture, bacterial species were identified by VITEK2 Compact system and BD-Bruker MALDI Biotyper system. Drug resistance was detected by K-B agar diffusion method recommended by CLSI. Results: A total of 392 strains of bacteria were isolated from 327 patients distributed in 21 genus and 56 species, of which 225 were gram-positive cocci (57.40%), 114 were gram-negative rods (29.08%), 46 were gram-positive rods (11.73%), and 7 were gram-negative cocci (1.79%). The top 3 bacteria were Staphylococcus aureus 91(23.21%), Staphylococcus epidermidis 42 (10.71%), and Pseudomonas aeruginosa 24 (6.12%). Staphylococcus had a high rate of resistance to penicillin and erythromycin (>50%). Gram-negative rods were resistant to ampicillin (86.1%), and also had certain resistance to most second-generation and some third-generation cephalosporin (about 50%). There was no significant change in the drug resistance rate of MRSA compared to MSSA. Only the resistance rate to tetracycline was statistically different (P<0.05). Conclusion: The emergence of drug-resistant strains is an important factor leading to refractory infections. There are a wide range of pathogenic bacteria species among the skin and soft tissue infection patients, and antimicrobial drugs should be chosen wisely according to drug sensitivity.

Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses.

Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses.

The necessity of strength evaluation in assessment of clinical outcome after shoulder surgery : follow-up data from patients with complex proximal humerus fractures treated by locking plate fixation.

In order to minimize the bias of Constant score we modified the allocation of strength subscore. One hundred and two patients with 3- and 4-part proximal humerus fractures were treated using locking plate fixation and followed up for > 1 year. The clinical outcomes were assessed by DASH score abbreviated Constant score (AbbCS strength item excluded) modified Constant score (ModCS with 12-pound strength) and original Constant score (CS with 25-pound strength). The satisfaction rate was determined for each scoring instrument. Compared to CS the satisfaction rate was significantly higher in DASH score AbbCS and ModCS (all p < 0.001) but the latter 3 groups did not show significant difference. ROC analysis showed that a > 7-pound shoulder strength was present in patients with satisfied outcome assessed by DASH score. In conclusion strength evaluation is necessary for the assessment of shoulder function but the over-allocated strength should be modified in Constant score.

The influence of continuous glucose monitoring of high-risk neonate on guiding perinatal complications and one-year follow-up results.

OBJECTIVE: To investigate the value of micro blood glucose monitoring of high risk neonate on guiding perinatal complications and one-year follow-up results. PATIENTS AND METHODS: A total of 268 cases that were diagnosed as high-risk neonates by our Obstetrics Department from June 2010 to June 2014 were enrolled. After measuring their micro blood glucose instantly, 6h, 12h, 24h, 1d, 2d and 3d after delivery, divided them into two groups: hypoglycemic group (n = 54) and normal group (n = 214). And then the differences of perinatal complications and their one-year follow-up results were compared. RESULTS: The occurrence of perinatal complications in hypoglycemic group was significantly higher than that in normal group (p < 0.05); the faster the hypoglycemia occurred, the longer the duration was, and the severer the complications were. Hypoglycemia often occurred prior to the complications. The mental development index (MDI) and the physical development index (PDI) of hypoglycemic group were significantly lower than those in the normal group and differences were statistically significant (p < 0.05). CONCLUSIONS: Continuous blood glucose monitoring of high-risk neonate was of great significance in guiding perinatal complications at one-year follow-up.

Anti-nephrolithic potential of catechin in melamine-related urolithiasis via the inhibition of ROS, apoptosis, phospho-p38, and osteopontin in male Sprague-Dawley rats.

The addition of melamine to infant formula may cause urolithiasis in humans and animals. This study examined the effects of catechin, an antioxidant, on melamine-cyanuric acid mixture (MCM)-induced crystallization in vitro and in vivo. In an in vitro study, crystal formation induced by an MCM was evaluated in media under various pH conditions and with catechin co-treatment. In an in vivo study, rats were administered an MCM (400 mg/kg, 1:1, via oral feeding tube) for four weeks and co-treated with catechin, after which crystal formation was observed. Oxidative stress biomarkers and nephrotoxicity were measured. Apoptotic cells were examined using the TUNEL assay. Phospho-p38 and osteopontin were evaluated via immunohistochemistry and Western blotting. MCM-induced crystal formation was pH-dependent in conditioned media, and catechin reduced the overall number of crystals. In the in vivo study, catechin suppressed MCM-induced protein expression and apoptosis in rats. Catechin consistently reduced the MCM-mediated production of renal malondialdehyde (MDA) and urinary 8-isoprostane (8-IP) in MCM-treated rats. The activities of antioxidant enzymes such as superoxide dismutase (SOD) were enhanced by catechin. Catechin consistently and significantly reduced levels of renal crystals and nephrotoxicity. Our findings suggest that catechin exhibits anti-nephrolithic potential by chemically inhibiting the formation of crystals and by inhibiting reactive oxygen species, apoptosis, phospho-P38, and osteopontin signaling in rats.

Expression and hypoxia adaptation analysis of the EPO gene in different tissues of plateau Tibetan pigs.

This study aimed to observe the expression characteristics of the erythropoietin (EPO) gene in different tissues of Tibetan pigs and to explore the adaptation to hypoxic environments. The cDNA in heart, liver, lung, kidney, muscle, brain, and fat of Tibetan pigs was used as the template. Through the number of cycles of the polymerase chain reaction (PCR), annealing temperature, and system optimization, a stable and specific semi-quantitative PCR system was established. The EPO gene in different tissues of Tibetan pigs was detected using this system. The results showed that the EPO gene was expressed in heart, liver, lung, kidney, muscle, brain, and fat of the pigs. There were obvious differences in the expression in each tissue, and the expression sequence was as follows: kidney > muscle > lung > brain > liver > heart > fat. The results showed that the EPO gene was expressed in various tissues of Tibetan pigs. There were obvious differences in expression and each tissue may play a different regulatory role in the adaptation to hypoxia.

Histological characteristics of induced membranes in subcutaneous, intramuscular sites and bone defect.

BACKGROUND: The induced membrane technique was proposed as a treatment of large segmental bone defects. The influence of the surrounding tissues on its characteristics remains unknown. It is therefore not known which kind of plastic surgery procedure (muscular or facio-cutaneous flap) would optimize bone osteointegration within a bone defect reconstructed using the induced-membrane technique. HYPOTHESIS: We hypothesized that membrane characteristics could be influenced by the soft-tissue environment either subcutaneous or muscular. OBJECTIVE: To evaluate the histological characteristics of poly-methylmethacrylate (PMMA) induced membranes in intramuscular, subcutaneous and bony environment (radius defects) at 2 steps: spacer implantation; secondary bone graft and its subsequent osteintegration after spacer removal. METHODS: PMMA-induced membranes were obtained in the three sites of 15 rabbits. Subsequent new bone formation was studied in the same environments in 24 other rabbits. Six weeks after the initial implantation, PMMA spacers were replaced with iliac autografts. Animals were euthanized at 2, 4, and 8 weeks postoperatively. Tissue samples were harvested and stained with hematoxylin and eosin. The histological characteristics of the membrane (thickness and microvessel density) and the newly-formed bone (cortical thickness) were quantitatively analyzed. RESULTS: The membranes in the subcutaneous sites developed quicker, were thicker and had the lowest microvessel density (P<0.01). The membranes in the intramuscular sites developed later and were thinner (P<0.01). The membranes in the osseous defects had the greatest microvessel density (P<0.01). After bone grafting, induced membranes became thinner and their microvessel density decreased substantially, but maintained better in osseous site. The newly-formed bone that developed in the radius defects, had the thickest cortices (P<0.01). CONCLUSIONS: The evolution of membranes induced in the intramuscular and subcutaneous environments was close to that of the bone defect model, although bone formation appeared weaker.

Evolution of testis-specific kinases TSSK1B and TSSK2 in primates.

The testis-specific serine/threonine protein kinases TSSK1 and TSSK2 are known to be essential for male fertility, in mice. The enzymes are present in elongating spermatids, and targeted deletion of the two genes Tssk1 and Tssk2 results in dysregulation of spermiogenesis. The mouse genes are genetically closely linked, forming a Tssk1-Tssk2 tandem. In human, TSSK1 is present in the form of a pseudogene, TSSK1A, which is linked to an intact TSSK2 gene, and in the form of an intact gene, TSSK1B, which is not genetically linked to TSSK2. Studies on conservation of genes and gene function between mouse and human are relevant, to be able to use mouse models for studies on human infertility, and to evaluate possible targets for non-hormonal contraception targeting the male. Therefore, we have performed a detailed analysis of the evolution of genes encoding TSSK1 and TSSK2 among mammals, in particular among primates. This study includes functional analysis of replacement mutation K27R in TSSK2, which is frequently observed among humans. In primates, the kinase domains of TSSK1B and TSSK2 have evolved under negative selection, reflecting the importance to maintain their kinase activity. Positive selection was observed for the C-terminal domain of TSSK1B, which indicates that TSSK1B and TSSK2 may perform at least partly differential functions.

Design of shared instruments to utilize simulated gravities generated by a large-gradient, high-field superconducting magnet.

A high-field superconducting magnet can provide both high-magnetic fields and large-field gradients, which can be used as a special environment for research or practical applications in materials processing, life science studies, physical and chemical reactions, etc. To make full use of a superconducting magnet, shared instruments (the operating platform, sample holders, temperature controller, and observation system) must be prepared as prerequisites. This paper introduces the design of a set of sample holders and a temperature controller in detail with an emphasis on validating the performance of the force and temperature sensors in the high-magnetic field.

Crack propagation of single crystal beta-Sn during in situ TEM straining.

In situ tensile process of single-crystal Sn was investigated by transmission electron microscopy (TEM). Despite the traditional wedge microcrack, a new tetragonal microcrack was observed during crack propagation in the single-crystal Sn. During in situ tensile straining, the dislocation dipoles formed at the front of the wedge microcrack tip, the coalescence of which is the source of microvoids at the crack tip, and then the wedge microcrack propagated deeply by aggregation of discontinuous microvoids. The tetragonal microcrack propagated by the intersection along two vertical slip planes. Moreover, the series of high-resolution images showed that Sn islands formed at the center of the frontier crack plane due to the anisotropic self-diffusion of Sn atoms along different crystallographic planes.

Sural nerve grafting in robotic laparoscopic radical prostatectomy: interim report.

BACKGROUND AND PURPOSE: Sural nerve grafting for patients undergoing prostatectomy has been previously reported using open and minimally invasive methods. We report our experience with sural nerve grafting during robot-assisted laparoscopic radical prostatectomy (RLRP). MATERIALS AND METHODS: Patients with preoperative potency and a minimum of 6 months follow-up were included in this prospective review. A total of 333 patients were identified between February 2003 and January 2006 who met these criteria including 22 of the 25 patients who underwent sural nerve grafting. Patients were divided into 5 groups to compare unilateral and bilateral sural nerve cohorts with non-nerve-sparing and unilateral and bilateral nerve-sparing groups. Patients were followed prospectively using health-related quality-of-life questionnaires. RESULTS: Twenty-two patients underwent sural nerve grafting that included three bilateral grafts. Mean follow-up was 14 months. There was no statistical difference in patients' ages, body mass index, preoperative prostate-specific antigen level, blood loss, complications, and positive margin rate. Operative time was statistically longer for both sural graft cohorts when compared with unilateral (without graft) and bilateral nerve sparing cohorts. No significant differences in subjective or objective sexual function, sexual bother, or urinary function were seen with 6 and 12 months follow-up, possibly related to smaller sural cohorts. Graft-related complications include leg pain in one patient. CONCLUSION: Sural nerve grafting during RLRP is technically feasible and safe and offers improved dexterity and visualization deep within the pelvis. However, a larger randomized cohort of patients will be required to validate any improved benefits afforded by the robot system.

The role of atomic scale investigation in the development of nanoscale materials for information storage applications.

It is well established that the response of devices based on the giant magnetoresistance (GMR) effect depends critically on film microstructure, with parameters such as interfacial abruptness, the roughness and waviness of the layers, and grain size being crucial. Such devices have applications in information storage systems, and are therefore of great technological interest as well as being of fundamental scientific interest. The layers must be studied at high spatial resolution if the microstructural parameters are to be characterized with sufficient detail to enable the effects of fabrication conditions on properties to be understood, and the techniques of high resolution electron microscopy, transmission electron microscopy chemical mapping, and atom probe microanalysis are ideally suited. This article describes the application of these techniques to a range of materials including spin valves, spin tunnel junctions, and GMR multilayers.

[Experimental study of bone repair induced by cryopreserved allograft periosteum and fetal bone composition in bone defect].

OBJECTIVE: To investigate the repairing effect of transplantation of allogeneic fetal bone in combination with a covering cryopreserved periosteal allograft to bone defect. METHODS: Twenty Long-eared white male rabbits were chosen as experimental model of bilateral 12 mm combined bony and periosteal radial defect. Cryopreserved allograft periosteum with allogeneic fetal bone were implanted in the left defect as experimental side and fetal bone was simply transplanted in the right defect as control side. Bone repair process in the two groups were compared by macroscopy, microscopy, roentgenograms and the contents of calcium and phosphate in the defect area at 2, 4, 8 and 12 weeks after transplantation. RESULTS: There was significant statistic difference in the contents of calcium and phosphate between the experimental and control sides at 4, 8 and 12 weeks after transplantation (P < 0.05). With time passing by, the contents of calcium and phosphate have the increasing trends. In the experimental group, lamella bone was seen and medullary canal recanalized at 8 weeks postoperatively. The histological section showed the bone lacuna and lamella bone were formed. CONCLUSION: It suggests that allogeneic fetal bone in combination with a covering cryopreserved periosteal allograft can promote bone repair, and allogeneic fetal bone is excellent bone substitute.

Study of the gastrointestinal protective effects of polysaccharides from Angelica sinensis in rats.

We studied the protective effects of polysaccharides isolated from the root of Angelica sinensis (Oliv.) (Danggui) on gastrointestinal damage induced by ethanol or indomethacin in rats. Oral administration of ethanol provoked a marked hemorrhagic damage in the glandular mucosa, which was accompanied with a significant increase of myeloperoxidase (MPO) activity, a marker enzyme for inflammation and neutrophil infiltration. An extract from Angelica, which mainly consisted of polysaccharides (95%) (AP), dose-dependently prevented gastric mucosal damage. This ulcer protective effect could last at least 12 h after administration. Prostaglandin E2 produced a similar anti-lesion effect. AP and prostaglandin E2 also reduced mucosal MPO activity. Indomethacin-induced gastrointestinal damage, another neutrophil-dependent lesion model in the gastrointestinal tract, was also prevented by AP pretreatment. The present findings suggest that polysaccharides from Angelica possess an anti-inflammatory action, perhaps through the inhibitory action on neutrophil infiltration in the gastrointestinal mucosa. AP could potentially be useful to prevent any neutrophil-dependent mucosal injury in the gastrointestinal tract.

Purification and characterization of human hepatic stimulator substance.

Human hepatic stimulator substance (hHSS) was purified from fetal liver with 6,000-fold decrease in protein content and 840-fold increase in specific growth stimulative activity. Purification procedures included the heating of a homogenate in 35% (W/V) Tris-HCL at 95 degrees C for 20 min, high and ultra speed centrifugation, passage over Sephadex G100 gel filtration, DEAE-cellulose ion exchange, TSK G3000 SWG high performance liquid chromatography (HPLC) and YWG C-18 reverse phase HPLC techniques. The most purified material (HP-HSS) revealed cell-specific and dose dependent increase in 3H-TdR incorporation into cellular DNA. As little as 38 ng of the HP-HSS per ml of culture medium produced a 2.5-fold increase in DNA synthesis. Further studies indicate that HP-HSS in combination with insulin and epidermal growth factor stimulate DNA synthesis 16-fold compared with serum and hormone free controls and nearly 3-fold over hepatoma growth with HP-HSS alone. Sodium dedecyl sulfate polyacrylamide gel electrophoresis with silver stain and ultrascan XL laser densitrometer quantitative scanning revealed only one band at 12,800.