Objective To investigate the radiographic anatomical relationship between tibial plateau and distal femur and evaluate the impact of reset tibial plateau of various widths after reduction of the Schatzker Ⅳ-C tibial plateau fractures on postoperative outcomes.Methods We collected and reviewed the X-ray images of the normal knees of 207 standard neutrally-positioned adults(non-fracture group)and pre-and post-operative immediate anterior-posterior X-ray images of the knees of 60 patients with Schatzker Ⅳ-C fractures(fracture group)in our hospital from August 2012 to August 2022.We measured the proximal tibial joint width(TAW),distal femoral width(DFW),and distal femoral joint width(FAW)in both groups and calculated the TAW/DFW and TAW/FAW ratios.In the fracture group,the cases with TAW between FAW and DFW were assigned to the well-reduced group,while those with TAW outside this range between FAW and DFW to the poorly-reduced group.Both groups were assessed using the Hospital for Special Surgery knee score(HSS)one year after operation.Results In the non-fracture group,there were no significant differences in gender or affected side in terms of TAW/DFW and TAW/FAW ratios(P＞0.05),while in the fracture group,there were statistically significant differences in the TAW/DFW and TAW/FAW ratios compared to the non-fracture group(P＜0.05).There was a statistically signifi-cant difference in the one-year postoperative HSS scores between the well-reduced and poorly-reduced groups in the fracture group(P＜0.05).Conclusion The radiographic anatomical relationship between the tibial plateau and distal femur in normal adults is relatively constant,providing a radiological reference for resetting the tibial plateau to a satisfactory width during reduction of Schatzker Ⅳ-C fractures.TAW/DFW＞1 or TAW/FAW＜1 indicates a poor reduction of the fracture and predicts poor postoperative recovery of knee joint function.

Oligonucleotide drugs have experienced accelerated development in the past 10 years, and some of them have been used in clinical treatment. Because of its convenient design, flexible sequence, and high specificity, it is expected to solve the “undruggable” challenge of many targets which are difficult in drug development. Moreover, its clinical transformation period and cost are relatively low, which makes oligonucleotide drug become the frontier of emerging biotechnology drug discovery. Brain diseases include a series of incurable diseases, such as neurodegenerative diseases, glioma, and motor neuron diseases. Many of them are age-related and regarded as aging-associated brain diseases. Due to the complex etiology, many targets are difficult to be drugged. At the same time, the existence of the barrier system “blood-brain barrier” in the brain makes most drugs unable to achieve effective accumulation at brain lesions, and many small molecule drugs have failed in clinical transformation. The specificity and sequence flexibility of oligonucleotide acid drugs provide new possibilities for drug development, but they also face the challenge of brain delivery. Although a variety of oligonucleotide drugs have been used in the medical market, brain-targeted oligonucleotide drugs are still extremely rare. This article reviewed recent advances and discussed key topics and clinical transformation challenges in this field, such as clinical approval cases, bottlenecks of brain-targeted delivery and current strategies, as well as potential targets for aging-related brain diseases.

OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023， fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group （n＝3 750）， and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group （n＝ 3 706）. Self-reported indicators of patients were collected through telephone follow-up at 0， 4， 7 and 14 days after treatment. The improvement values of pain score， swelling score and health utility value， as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score （PSM） method was adopted to perform baseline matching on patient’s age， gender， fracture site， fracture severity， surgical type， type of hospital， and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM， a total of 6 425 patients were included， of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment， the observation group showed significant improvement in pain score （4.768 vs. 4.353）， swelling fangshiyuan2008@126.com grading score （2.979 vs. 2.391）， and life quality utility value （0.430 vs. 0.363）， as well as effective rate （87.20% vs.75.99%） compared to the control group （P＜0.05）. The results of subgroup analyses conducted by gender， age， hospital type， and fracture site were consistent with the aforementioned results. In terms of safety， the observation group had no serious adverse reactions， with a total of 29 cases of mild adverse reactions such as dizziness， stomach pain， and allergies， with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain， swelling， quality of life， and effective rate in patients with fractures， and have good safety.

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg^-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ² test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×10⁹/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ²=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ²=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.
Male ; Female ; Humans ; Child ; Prognosis ; Philadelphia Chromosome ; Retrospective Studies ; Receptor, Platelet-Derived Growth Factor beta/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Neoplasm, Residual

[Abstract] The circular RNA (circRNA) is a class of endogenous expressed non-coding RNA that are formed by covalently closed cyclization through reverse splicing. In recent years, a variety of highly conserved and cell-type specific circRNA have been identified in eukaryotes. Alzheimer’ s disease (AD) is a common neurodegenerative disease and the most common cause of dementia in the elderly. Recent studies had shown that circRNA was involved in the pathogenesis and development of AD, such as amyloid β-protein (Aβ) metabolic, neuroinflammation, oxidative stress, autophagy and synaptic plasticity. The role and application value of circRNA in AD pathology are reviewed to provide a theoretical basis for the application of circRNA in the treatment and diagnosis of AD.

A new rapid, quality control method based on quantitative water tests has been established for the quality evaluation of Indigo Naturalis. The Turbiscan stability index (TSI) of 26 batches of Indigo Naturalis was measured by a stability analyzer. The parameters, including the method by which the ingredients are added, their particle size, amount, and the testing temperature, were systematically optimized and the methodological indexes such as repeatability and stability were determined. The content of indigo and indirubin in 26 batches of Indigo Naturalis was determined by high performance liquid chromatography and the total ash was measured. The correlation analysis between the active ingredients, total ash content and TSI value of Indigo Naturalis was determined by SPSS 26.0 and Origin 2021. This research shows that the best way to prepare samples for testing is to add 0.2 g of Indigo Naturalis powder which has passed through a No. 7 sieve but failed to pass through a No. 9 sieve to a glass bottle containing 20 mL pure water by a funnel and scan at 25 ℃ with a stability analyzer. Consistency analysis showed that the content ranking of indigo and indirubin is opposite to the TSI value, and the content ranking of total ash is generally consistent with the TSI value. Correlation analysis showed that the correlation coefficients of indigo and indirubin content and TSI value were -0.850 and -0.801, respectively, and R² was 0.72 and 0.64. The correlation coefficient between total ash content and TSI value was 0.724, R² was 0.52. Using the change in TSI value of Indigo Naturalis powder in water, this study establishes the range of classification of Indigo Naturalis decoction pieces and the content of relevant components, which can be used to authenticate Indigo Naturalis and evaluate its quality.

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Xianling Gubao is a common and effective medicine in the treatment of orthopedic diseases. In recent years, it has been reported to be associated with liver injury. However, through the analysis of the adverse drug reaction reports and key hospital cases, we found that there is considerable incomplete information in the reports of Xianling Gubao-related liver injury cases retrieved from the literature. Thus, it is difficult to accurately judge causality between the drug and liver injury. Six cases of liver injury related to Xianling Gubao were identified in key hospitals, two of which achieved the clinical diagnosis according to the assessment of the integrated evidence chain method. We further analyzed the public health data of all residents in Yinzhou. The gross incidence rate of Xianling Gubao-related liver injury was 0.034%, which corresponds to a level of rare incidence. This revealed that Xianling Gubao-related liver injury has significant divergence in individuals and an idiosyncratic nature. The gross incidence of liver injury related to Xianling Gubao was lower than that of other medicines for the treatment of orthopedic diseases. Based on the idiosyncratic drug-induced liver injury model mediated by immune stress, it was found that Epimedii Folium and Psoraleae Fructus were the major components that lead to liver injury, and the liver injury caused by a full prescription was less serious than that encountered with only Epimedii Folium and Psoraleae Fructus. This suggests that the other 4 herbs (Dipsaci Radix, Anemarrhenae Rhizoma, Rehmanniae Radix,Salviae Miltiorrhizae Radix et Rhizoma) can prevent/alleviate the liver injury. Through disassembled prescription analysis, we found that the attenuation efficacy of Salviae Miltiorrhizae Radix et Rhizoma was the most significant. In conclusion, Xianling Gubao may cause idiosyncratic liver injury in a tiny minority of susceptible individuals, but the incidence risk is lower than that of other commonly used drugs for orthopedic disease. Xianling Gubao should be discreetly applied to patients with immune stress. The major components that induced liver injury in Xianling Gubao were Epimedii Folium and Psoraleae Fructus, and Salviae Miltiorrhizae Radix et Rhizoma appears to attenuate this toxicity. This study provides a reference for the rational clinical medication with Xianling Gubao.