Abstract: As potential immunomodulators, platinum-based drugs could trigger immunogenic cell death (ICD). Hence, combination of platinum-based chemotherapy and immunotherapy could have better synergistic anticancer effect. Pt(II)-based drugs are the most common chemotherapeutic agents in cancer treatment yet with limited clinical application due to their toxic side-effects and drug resistance. Pt(IV) complexes have been widely investigated in the past decades due to their kinetic inertness and unique mechanisms . This article summarizes the progress in the pharmacological activities and mechanisms of Pt(IV) antitumor complexes via introducing different immunomodulators into chemotherapeutic agents in literature over recent years and highlights the potential targets and molecular signaling pathways so as to provide some reference for further development and potential clinical application of platinum-based chemo-immunotherapeutic agents.

Objective:To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice.Methods:Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People′s Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results:The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35, P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81, P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion:Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i^-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i^-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i^-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i^-/- odontoblasts. Through treating pulp precursor cells with Atp6i^-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i^-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i^-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.
Female ; Animals ; Mice ; Transforming Growth Factor beta1 ; Odontoblasts ; Culture Media, Conditioned ; Cell Differentiation ; Signal Transduction ; Disease Models, Animal ; Tooth Root

Objective:To investigate the difference of curative effect between zero-profile bridge-shaped locking cage (ROI-C) and anterior cage combined with titanium plate fixation in the treatment of two-level and three-level cervical spondylotic myelopathy.Methods:A total of 85 patients (43 males and 42 females), aged 52.3±8.0 years (range from 28 to 66 years) with bi- and three-level cervical spondylotic myelopathy who received surgical treatment from June 2017 to October 2019 were retrospectively analyzed. There were 63 cases of two levels and 22 cases of three levels. 45 cases were treated with zero-profile bridge-shaped locking cage ROI-C (ROI-C group), and 40 cases with anterior cage combined with titanium plate fixation (titanium plate group). The main observation indicators include operation time, intraoperative blood loss, cervical Cobb angle, fusion segment Cobb angle, average intervertebral height, pain visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) Score and neck disability index (NDI).Results:All of 85 patients were followed up for 16.9±2.0 months (range 12 to 22 months). The operation time of two-level ROI-C group was 110.37±8.25 min, which was shorter than 139.5±10.54 min of titanium plate group; the intraoperative blood loss was 15.74±8.10 ml, which was less than 23.71±9.70 ml of titanium plate group; the operation time of three-level ROI-C group was 130.00±5.70 min, which was shorter than 162.83±5.59 min of titanium plate group, while the difference in the intraoperative blood loss between the two groups had no statistical significance. One year after operation, Cobb angle of cervical vertebra in double and three-level ROI-C groups were 15.31°±1.55° and 15.20°±0.42°, respectively, which were largerthan 11.23°±2.03° and 9.20°±1.14° before operation; in titanium plate group, they were 15.89°±1.13° and 16.08°±1.88°, which were higher than 11.25°±2.01° and 9.00°±1.60° before operation, and the differences had statistical significance. The differences between the two groups before operation and 1 year after operation had no statistical significance. One year after operation, the VAS scores of double and three-level ROI-C groups were 1.83±0.66 points and 2.60±0.52 points, respectively, which were less than the preoperative 7.49±0.51 points and 7.60±0.52 points; the titanium plate group was 1.79±0.50 points and 2.41±0.51 points, which were less than the preoperative 7.61±0.63 points and 7.42±0.52 points, and the differences had statistical significance. There was no significant difference between the two groups before operation and 1 year after operation. One year after operation, the JOA scores of double and three-level ROI-C groups were 15.00±0.84 points and 14.70±0.95 points, respectively, which were higher than the preoperative 7.20±0.87 points and 6.60±1.27 points; the scores of titanium plate group were 15.29±0.85 points and 14.83±0.58 points, which were higher than the preoperative 6.89±1.03 points and 6.92±0.67 points, and the differences had statistical significance. The differences between the two groups had no statistical significance. The postoperative JOA improvement rate was excellent. Postoperative dysphagia occurred in 1 case (2.22%, 1/45) in ROI-C group and 8 cases (20.00%, 8/40) in titanium plate group, and the difference in the incidence rate between two groups had statistical significance ( χ2=5.32, P=0.02). Conclusion:Both ROI-C and anterior cage combined with titanium plate fixation in the treatment of double and three-level cervical spondylotic myelopathy can achieve good short-term clinical efficacy, with shorter operation time and lower incidence rate of postoperative dysphagia using ROI-C.

Histone acetylation is one of the most important reactions of post-translational modification of histones, which plays an important role in the regulation of epigenetic processes. Histone deacetylase 2 as a member of type I histone deacetylases,involved in the catalytic regulation of histone and a variety of non-histone deacetylation,regulates a variety of life processes. This paper summarizes the basic structure of histone deacetylase 2 and the role of histone deacetylase 2 in various diseases,and provides a theoretical basis for conducting related studies.

Objective To discuss different performance of DR and CT examination on secondary pulmonary tuberculosis,to improve the clinical guidance value of CT in the diagnosis of secondary pulmonary tuberculosis. Methods The image data of 52 cases with secondary pulmonary tuberculosis confirmed by pathology were collected, including chest DR radiography and CT scans.The different image characteristics of two kinds of imaging examination were analyzed and compared.Results In 52 cases of secondary pulmonary tuberculosis,chest X -ray plain film found lesions calcification in 3 cases,2 cases of bronchiectasis,pleural thickening and adhesion in 12 cases,pleural effusion in 1 case,empty cavity in 4 cases,emphysema in 1 case,the lung nodules in 5 cases.Chest CT revealed lesions calcification in 9 cases,16 cases of bronchiectasis,pleural thickening and adhesion in 40 cases,pleural effu-sion in 4 cases,empty cavity in 10 cases,emphysema in 8 cases,the lung nodules in 10 cases,6 cases of pulmonary bullae,pulmonary interstitial change:4 cases of lung reticulocyte shadows,interlobular septal thickening in 4 cases, ground glass sample density in 4 cases.Conclusion DR and CT can be used for inspection of secondary pulmonary tuberculosis,but CT is a better tool,it has important guiding role for clinical diagnosis and treatment.

We investigated and analyzed the first case of human infection with avian influenza A(H9N2) virus in Yunnan Province,China,so as to provide a better basis for preventing and controlling human infections with viruses of animal origin in the future.We carried out the field epidemiological survey among the patient,close contacts and the live poultry markets,detected and analyzed the samples from patient and the outdoor environment.Results showed that the 9-month-old boy was a case of human infection with avian influenza A(H9N2) virus with the history of live poultry markets exposure and the results of nucleic acid detection and virus isolation.There was a lot of contamination of the avian influenza virus in the live poultry markets.The second generation cases have not occurred.The monitoring of pneumonia of unknown etiology and influenza like cases in medical institutions is the important means to find timely cases of human infected with avian influenza.Regular disinfection and closing-down of live poultry markets are key measures to reduce the exposure opportunity.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Objective To investigate the mutation of hemagglutinin gene and amino acid variation of influenza B.Methods Influenza B virus was isolated from throat swab samples in sentinel surveillance of Yunnan province from 2009 to 2014.HA1 gene sequence analysis was applied to determine 12 randomly-selected strains of influenza B virus.The results were analyzed,MEGA software was used to do homology comparison and HA gene phylogenetic tree was established.Results Differences on the serotype and genotype identification of influenza strains were found and it might be caused by inadequate gene mutation accumulation.Amino acid variations were found in 3 important regions of antigenic determinants in HA1 protein:ring 120,ring 150 and ring 160.The amino acid variation of position 131 in ring 120 was N131K,and in position 137 was N137H.Two strains had P187S mutation in position 187.Conclusion There are some important variations in the hemagglutinin gene of influenza B strains in Yunnan Province,with some variations being the same as vaccine strains and some being not.