Since the beginning of the 21st century,the field of cancer drug development has undergone significant changes.Kinase inhibitors are the product category with the highest number of approved drugs and indications.However,despite checkpoint inhibitors being only introduced to the market since 2011,they have become the second most approved product categories.In the year of 2023,the FDA's Center for Drug Evaluation and Research(CDER)has approved 13 new cancer therapeutic drugs.In the past five years,a slight increase in drug approvals targeting biomarker-defined populations as well as emerging approvals that are agnostic to tumor anatomy has been recorded.Currently,new treatment approaches and technologies,such as the development of Artificial Intelligence(AI),have increasingly profound progress on cancer drug development.

Objective To predict the mechanism of Danhong injection in acute myocardial infarction based on network pharmacology and molecular docking.Methods The chemical ingredients of Danhong injection were collected by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),while Swiss Target Prediction was used to predict the corresponding targets of ingredients.The targets of acute myocardial infarction were retrieved in human gene database(GeneCards),online Mendelian inheritance in man(OMIM)and gene-disease association database(DisGeNET).Venny 2.1 online software was used to obtain the common targets of drugs-disease,and then the"drug-compound-target-disease"network diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the protein-protein ineraction network,and the perform gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out through the database for annotation,visualization,and integrated discovery(DAVID),and the AutoDock platform was applied in verifying the molecular docking of active components and protein targets.Results The 63 active components of Danhong injection could regulate 137 targets and 132 pathways to treat acute myocardial infarction.Przewaquinone C,luteolin,baicalein,sclareol,kaempferol,quercetagetin and other active compounds,which could mediate C-type lectin receptor,tumor necrosis factor,endocrine resistance,prolactin,phosphatidylinositol-3-kinases-serine/threonine protein kinase,Janus-activated kinase singal transducers and activators of transcriprion and other signaling pathways through tumor necrosis factor,RAC-alpha serine/threo-nine protein kinase,interleukin-1 beta,steroid receptor coactivator,mitogen-activated protein kinase 3,signal transducer and activator of transcription 3 and other key target proteins.The result of molecular docking showed that the targets and the components had a certain degree of binding.Conclusion Danhong injection can participate in the treatment of acute myocardial infarction through multiple components,targets and pathways,which provides a theoretical basis for the clinical application of Danhong injection and the mechanism of its treatment of acute myocardial infarction.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-β(TGF-β)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-β/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-β/Smad signaling pathway. This study clarified the mechanism of TGF-β/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-β/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.
Humans ; Diabetic Nephropathies/genetics* ; Medicine, Chinese Traditional ; Kidney/pathology* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Epithelial-Mesenchymal Transition ; Smad Proteins/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Diabetes Mellitus/genetics*

Lung cancer is the highest cancer-related mortality rate in the world, and is one of the most common malignancies. The standard treatment for early-stage non-small cell lung cancer (NSCLC) is radical lobectomy, while recent studies have found that sub-lobectomy of pulmonary nodules (≤2 cm) is not inferior to lobectomy and even improve the prognosis of the patients. These important findings will effectively and positively promote the formation of consensus and principles of wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The purpose of this study is to present a national expert consensus on wedge resection of pulmonary nodules (≤2 cm) in the field of thoracic surgery. The experts from Editorial Committee of Consensus on Wedge Resection of Lung Nodules (≤2 cm) (2023 Edition) jointly participated in the revision work. According to the clinical progress about the wedge resection of pulmonary nodules (≤2 cm) at home and abroad during recent years, experts jointly wrote Wedge Resection of Pulmonary Nodules (≤2 cm): a Consensus Statement by Specialists of Thoracic Surgery (2023 Edition), in combination with the homogeneous treatment principles of wedge resection in the field of thoracic surgery in China. This consensus was summarized from the following aspects: (1) Indications of wedge resection of pulmonary nodules (≤2 cm); (2) Resection range of pulmonary nodules (≤2 cm) required for wedge resection; (3) Excisable pulmonary nodules (≤2 cm) for wedge resection. This consensus finally put forward 8 recommended opinions, and sorted out 5 opinions which were still controversial and needed more evidence. The integrated opinions were generated through the discussion held among the experts of thoracic surgery from all over the country, making wedge resection of pulmonary nodules (≤2 cm) more appropriate for China and more standardized and homogeneous for clinical practice. In the future, more relevant researches should be accumulated based on the characteristics of lung cancer and its diagnosis and treatment in China, optimizing the treatment of pulmonary nodules (≤2 cm).
Humans ; Thoracic Surgery ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms/surgery* ; Thoracic Surgical Procedures ; Multiple Pulmonary Nodules ; Small Cell Lung Carcinoma

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

[ Abstract ] Objective To explore the effect of 3D print-based navigation module assisted placement of thoracolumbar pedicle screws. Methods From January 2019 to May 2021, we received 70 thoracic and lumbar fracture patients, divided into 3D technical group and conventional method group according to the surgical method, with 35 patients in each group. In the 3D technology group, pedicle screws were placed under the sight of the navigation module, while in the conventional group, pedicle screws were placed under the conventional C-arm fluoroscopy. The amount of intraoperative bleeding and time of C arm were counted in each patient. According to the different number of pedicle screw implantation in each patient, the average amount of blood loss, time and C-arm fluoroscopy times of each screw implantation were compared between the two groups. Ideal screw angles were designed for patients in both groups before surgery. Compared with the preoperative design, the difference between preoperative and postoperative screw angle and head angle was calculated and set as the deviation value. Two sets of data were compared. Visual analogue score(VAS), Japanese Orthopaedic Association (JOA) score, Oswestry disability index(ODI), vertebral height recovery ratio and Cobb’ s angle were compared between the two groups. Results The amount of blood loss, required time and exposure times of C-arm in 3D screw implantation group were significantly lower than those in conventional screw implantation group(P<0. 05); After operation, the deviation of ininclination and head angle in the conventional method group was higher than that in the 3D technique group, and the difference was significant(P<0. 05); The VAS, JOA score, ODI, vertebral height recovery ratio and Cobb’s angle were significantly improved compared with the preoperative groups(P<0. 05); Three months after surgery, the VAS, JOA score, and ODI were not significantly different between the two groups (P>0. 05); In terms of Cobb’s angle and vertebral height recovery ratio, the 3D technique group was better than the conventional method group (P<0. 05). Conclusion The 3D printed navigation module can assist the precise placement of thoracolumbar pedicle screws, shorten the operation time, reduce intraoperative bleeding and c-arm exposure times, facilitate the recovery of the injured vertebral height, improve the efficacy.

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models