The complete chloroplast genome sequence of Zanthoxylum ailanthoides Sieb. et. Zucc (Rutaceae): an important medicinal plant.

Zanthoxylum ailanthoides is a deciduous tree, with important medicinal and economic values. The complete chloroplast genome sequence of Z. ailanthoides was assembled and the phylogenetic relationship to other species was inferred in this study. The chloroplast genome is 157,209 bp in length, including two inverted repeats of 26,408 bp, a large single-copy of 86,099 bp and a small single copy of 18,294 bp. Moreover, the chloroplast genome contains 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the chloroplast genome is 38.4%. The phylogenetic analysis indicated that Z. ailanthoides was grouped with a clade containing the species of Z. multijugum, Z. calcicola, Z. oxyphyllum, Z. stenophyllum, and the genus was closely related to Phellodendron. This study contributes to a better understanding of the phylogenetic relationships among Zanthoxylum species.

Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

[Role of macrophage polarization in pulmonary diseases and intervention of traditional Chinese medicines].

As important immune cells, macrophages are a key factor involved in maintaining the homeostasis of the pulmonary microenvironment. Under different conditions, macrophages with high plasticity can be polarized into classically activated(M1) and selectively activated(M2) macrophages, which have pro-inflammatory and anti-inflammatory effects, respectively. M1/M2 phenotype is associated with the occurrence and development of pulmonary diseases. A variety of information molecules and cytokines involved in the polarization of macrophages play a role in regulating phenotypes in pulmonary diseases, and the phenotype transformation varies significantly in different diseases. This paper introduces the biological characteristics of macrophage polarization and expounds the roles of macrophage polarization in bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, and pulmonary fibrosis. Moreover, the research progress in the regulation of macrophage polarization by the active components in traditional Chinese medicine(TCM) and the TCM compound prescriptions in the treatment of pulmonary diseases was reviewed. This review aims to explore the potential of macrophage polarization in regulating pulmonary inflammation and provide new ideas for related clinical research.

[Molecular identification of animal species of Bufonis Venenum from secretions].

The animal species is one of the key factors affecting the quality of Bufonis Venenum. The quality of Bufonis Venenum derived from Bufo bufo gargarizans is significantly higher than that from B. melanostictus. Since Bufonis Venenum is from secretions, the conventional identification methods are difficult to identify the animal species due to the lack of the appearance and morphology of the animals. The rapid development of molecular identification technology has provided new methods for the identification of Bufonis Venenum. However, because of the low content and serve degradation of residual DNA in secretions, the research on the molecular identification of Chinese medicinal materials from secretions remains to be carried out. To understand the animal species of Bufonis Venenum, this study collected 83 samples of Bufonis Venenum, including 7 commercially available samples, 5 reference medicinal materials, and 71 animal samples from which Bufonis Venenum was prepared according to the method in the 2020 edition of the Chinese Pharmacopoeia. Different DNA extraction methods were used and compared, and the mitochondrial 16S rRNA gene fragments were amplified, on the basis of which the phylogenetic trees were built. Finally, molecular identification of the animal species of the samples was performed. The results showed that the DNA extracted from Bufonis Venenum by the reagent kit had good quality, and 16S rRNA sequences were successfully amplified from 80 out of the 83 samples. In addition, 71 16S rRNA sequences of the animal species of Bufonis Venenum were downloaded from GenBank. The phylogenetic trees constructed based on the neighbor-joining(NJ) method and the Bayesian inference(BI) method showed that the samples derived from B. bufo gargarizans and B. melanostictus were clustered into separate monophyletic clades, with the support of 100%(NJ) and 1.00(BI), respectively. The animal species of both commercially available samples and reference medicinal materials were B. bufo gargarizans. In conclusion, DNA can be extracted from Bufonis Venenum derived from secretions, and the 16S rRNA gene sequences can be amplified, which can be used for molecular identification of the animal species of Bufonis Venenum. The findings provide a reference for the quality control of Bufonis Venenum and the identification of animal species of medicinal materials derived from secretions.

The combined application of ear acupuncture in the treatment of allergic rhinitis: A meta-analysis.

Objective: Meta-analysis was used to evaluate the clinical efficacy of auricular acupressure in the treatment of allergic rhinitis. Methods: Randomised controlled trials (RCTS) on the treatment of allergic rhinitis with ear acupuncture were searched by computer in PubMed, Cochrane Library, Embase、Web of Science、China National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP database, and China Biomedical Literature Service System (CBM). The search time was from the establishment of the database to September 18, 2022. Meta-analysis was performed using RevMan 5.4 software. Results: A total of 15 papers with 1002 patients were included in the final study. ①Clinical efficiency: The clinical efficiency of ear acupuncture combined with control group was higher than that of control group, and the difference was statistically significant (P < 0.00001); ② Nasal symptom score: the effect of ear acupuncture combined with control group on allergic rhinitis on nasal symptoms was more obvious than that of control group, and the difference was statistically significant (P = 0.004); ③ Nasal itching symptom score: the efficacy of ear acupuncture combined with control group on allergic rhinitis on nasal itching symptom was significantly higher than that of control group, and the difference was statistically significant (P = 0.01). ④Sneeze symptom score: the effect of ear acupuncture combined with control group on allergic rhinitis on nasal itching symptom was more effective than that of control group, and the difference was statistically significant (P < 0.00001); ⑤Score of runny nose symptom: the effect of ear acupuncture combined with control group on allergic rhinitis on runny nose symptom was more obvious than that of control group, the difference was statistically significant (P = 0.004); ⑥Nasal congestion symptom scores: The effect of ear acupuncture combined with control group on allergic rhinitis on nasal congestion symptom was more obvious than that of control group, and the difference was statistically significant (P = 0.003). Conclusion: Ear acupuncture as an adjunctive therapy of allergic rhinitis can achieve better clinical efficacy.

Gastric cancer patient-derived organoids model for the therapeutic drug screening.

BACKGROUND: Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine. METHODS: PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs. RESULTS: We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone. CONCLUSION: PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

Iagnosis and treatment of myelitis after lumbar reoperation: A case report.

RATIONALE: At present, acute myelitis (AM) is a great challenge to diagnosis and treatment because of its complicated etiology, critical condition, and poor prognosis, and it is easy to leave different degrees of limb motor dysfunction. The report of this case is helpful to improve the understanding of AM after lumbar surgery, reduce misdiagnosis and provide reference for clinical treatment. PATIENTS CONCERN: This study reported a case of AM after lumbar reoperation. Before the patient was diagnosed as AM, we gave high-dose hormone anti-inflammatory and detumescence symptomatic treatment according to empirical treatment, and the effect was ideal and rehabilitation treatment was actively carried out at the right time. After 10 months of follow-up, the patient recovered well. DIAGNOSIS: Because lumbar surgery is a contraindication of lumbar puncture, the patient's diagnosis was confirmed by thoracic magnetic resonance imaging. Magnetic resonance imaging of thoracic vertebra on the 17th day after lumbar operation showed that small round T1W1 signal, slightly higher T2W1 signal and T2-fat suppression imaging equal signal were seen in the horizontal spinal cord of thoracic vertebra 10. INTERVENTION: According to the empirical treatment, patients have been given high-dose hormone therapy after operation, and comprehensive treatment such as comprehensive training of paraplegic limbs, joint loosening training, electric massage and other rehabilitation training will be carried out when the general condition of patients improves. OUTCOMES: After 10 months of follow-up, there were no major sequelae such as limb paralysis. CONCLUSION: Due to the rarity of AM in clinical work, it is easy for doctors to ignore the disease and miss the best treatment stage, which will lead to serious sequelae.

[Expert consensus on clinical application of Lixuwang~® Xuesaitong Soft Capsules].

Lixuwang~® Xuesaitong Soft Capsules(referred to as "Xuesaitong Soft Capsules") have the effects of promoting blood circulation, resolving blood stasis, and dredging meridians and collaterals. They are widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases in clinical practice. Through years of clinical observation, they have shown significant efficacy in ischemic stroke, coronary heart disease, and other diseases, and have been recommended by multiple guidelines, consensus statements, and monographs. Based on the summary of clinical application experience by doctors and existing evidence-based research, following the Technical Specifications for Consensus Development of Chinese Patent Medicine by Clinical Experts issued by Standardization Office of the Chinese Association of Traditional Chinese Medicine, a nominal group method was used to reach 19 recommended opinions/consensus suggestions. This document proposes the timing of medication, syndrome differentiation for medication, therapeutic effects, dosage and administration, treatment duration, economic considerations, and safety considerations in the use of Xuesaitong Soft Capsules for the treatment of ischemic stroke and angina pectoris in coronary heart disease. It is intended for doctors in internal medicine, encephalopathy(neurology), cardiovascular medicine, geriatrics, emergency medicine, general practice, and traditional Chinese medicine departments of various medical institutions, as well as pharmacists in hospitals and pharmacies, as a medication reference when using Xuesaitong Soft Capsules. It is hoped that the widespread application of this consensus can improve the clinical efficacy of Xuesaitong Soft Capsules in the treatment of ischemic stroke and coronary heart disease, promote rational drug use, and reduce medication risks. This consensus has been reviewed and published by the China Association of Traditional Chinese Medicine, with the identification number GS/CACM 323-2023.

Efficacy and safety of the Chaixiong Qiwei granule for tension-type headache: study protocol for a randomised controlled trial.

INTRODUCTION: Tension-type headache (TTH) is the most prevalent headache disorder worldwide. Although current treatments for TTH are beneficial, they are not without adverse effects. Chaixiong Qiwei granule (CXQW) is an experienced prescription medicine for TTH management. This study will evaluate the efficacy and safety of CXQW for the treatment of TTH. METHODS AND ANALYSIS: This study will be a multicentre, randomised, double-blind, placebo-controlled trial. A total of 148 eligible participants will be divided into the intervention (CXQW treatment) and control (placebo treatment) groups. The primary outcome will be the reduction in the number of headache days (headache-days reduction) within 9-12 weeks after randomisation, while secondary outcomes will include the number of headache days, headache intensity, responder rate, drug consumption for acute treatment, quality of life and symptoms related to traditional Chinese medicine use based on a symptom-observation table. This protocol describes the design of the randomised controlled trial. ETHICS AND DISSEMINATION: The study design was approved by the Institutional Review Board of Human Research at Xiyuan Hospital, China Academy of Chinese Medical Sciences (No. 2020XLA030-2). TRIAL REGISTRATION NUMBER: ChiCTR2100042514.

[Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Unraveling the protective mechanisms of Chuanfangyihao against acute lung injury: Insights from experimental validation.

Chuanfangyihao (CFYH) is an effective treatment for acute lung injury (ALI) in clinical practice; however, its underlying mechanism of action remains unclear. Therefore, the aim of the present study was to elucidate the pharmacological mechanism of action of CFYH in ALI through experimental validation. First, a rat model of ALI was established using lipopolysaccharide (LPS). Next, the pathological changes in the lungs of the rats and the pathological damage were scored. The wet/dry weight ratios were measured, and ROS content was detected using flow cytometry. ELISA was used to examine IL-6, TNF-α, IL-1ß, IL-18, and LDH levels. Immunohistochemistry was used to detect Beclin-1 and NLRP3 expression. Western blotting was performed to analyze the expression of HMGB1, RAGE, TLR4, NF-κB p65, AMPK, p-AMPK, mTOR, p-mTOR, Beclin-1, LC3-II/I, p62, Bcl-2, Bax, Caspase-3, Caspase-1, and GSDMD-NT. The mRNA levels of HMGB1, RAGE, AMPK, mTOR, and HIF-1α were determined using reverse transcription quantitative PCR. CFYH alleviated pulmonary edema and decreased the expression of IL-6, TNF-α, TLR4, NF-κB p65, HMGB1/RAGE, ROS, and HIF-1α. In addition, pretreatment with CFYH reversed ALI-induced programmed cell death. In conclusion, CFYH alleviates LPS-induced ALI, and these findings provide a preliminary clarification of the predominant mechanism of action of CFYH in ALI.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

NIR light-driven pure organic Janus-like nanoparticles for thermophoresis-enhanced photothermal therapy.

Photothermal therapy (PTT) represents a promising noninvasive tumor therapeutic modality, but the current strategies for enhancing photothermal effect have been mainly based on promoting thermal relaxation or suppressing radiative dissipation process of excited energy, leaving little room for further improvement in photothermal effect. Herein, as a proof of concept, we report the thermophoresis-enhanced photothermal effect with pure organic Janus-like nanoparticles (Janus-like NPs) for PTT. The Janus-like NPs are eccentrically loaded with compactly J-aggregated photothermal molecules (DMA-BDTO), which show red-shifted absorption wavelength and inhibited radiative decay as compared to individual molecules. Under NIR irradiation, the asymmetric heat generation at particle surface endows Janus-like NPs the active thermophoresis, which further increases collisions and converts kinetic energy into thermal energy, and Janus-like NPs exhibit significantly elevated temperature as compared to conventional NPs with homogenously distributed DMA-BDTO. Both in vitro and in vivo results confirm such thermophoresis-enhanced photothermal effect for improved PTT. Our new strategy of thermophoresis-enhanced photothermal effect shall open new insights for improving photothermal-related tumor therapy.

Three-Dimensional Speckle-Tracking Echocardiography to Evaluate Left Ventricular Function of Patients with Breast Cancer After Anthracycline Chemotherapy.

Objective: To explore the use of 3-dimensional speckle-tracking echocardiography (3DSTE) to evaluate changes in left ventricular function in patients with breast cancer after anthracycline chemotherapy. Methods: The clinical data of 30 patients with breast cancer diagnosed by pathology at The Third Affiliated Hospital of Qiqihar Medical University from December 2020 to December 2022 were collected for retrospective analysis. All patients received anthracycline chemotherapy, and serum cardiac troponin T (cTnT) concentrations were measured within 24 to 48 hours before chemotherapy and after 1 cycle and 4 cycles of chemotherapy. Then, conventional ultrasonography, routine echocardiography, and 3DSTE were performed to obtain dynamic images and parameters such as left ventricular global longitudinal strain, global area strain, global circumferential strain, global radial strain, and twist values. The myocardial comprehensive index was calculated to compare changes before and after anthracycline chemotherapy. A receiver operating characteristic curve was created for each parameter, and the areas under the curves were calculated. Results: Except for left ventricular end-diastolic diameter and end-diastolic interventricular septum thickness, the other conventional ultrasonography parameters differed at the 3 chemotherapy time points tested (all P < .001). The parameters as measured by 3DSTE decreased with an increased cumulative dose of anthracycline drugs, and the values differed at the different time points (all P < .001); the MCI value decreased the most. The serum cTnT concentrations of 9 patients after 4 cycles of chemotherapy were higher than the normal range, and the serum cTnT concentrations differed at the different chemotherapy time points (P < .001). Receiver operating characteristic curve analysis showed that the area under the curve value for MCI was higher than other quantitative parameters of imaging; for MCI, the area under the curve was 0.799, the Youden index was 0.683, the sensitivity was 77.80%, and the specificity was 90.50%. Conclusion: 3DSTE is helpful for early detection of damage to left ventricular function in patients with breast cancer treated with anthracycline drugs, and MCI is the most sensitive observation index among the parameters tested.

Mahuang Fuzi Xixin decoction ameliorates allergic rhinitis and repairs the airway epithelial barrier by modulating the lung microbiota dysbiosis.

Background: Allergic rhinitis (AR) is a common disorder, that burdens general well-being. Although the lung is connected to the upper respiratory tract, which is rich in microorganisms, no studies have reported the relationship between lung microbiota and AR. Mahuang Fuzi Xixin decoction (MFXD) is a traditional Chinese medicine (TCM) formula that is widely used to treat AR in the clinic but its underlying mechanism remains unclear. Hypothesis: We hypothesized that lung microbiota is associated with the pathogenesis of AR, and MFXD can improve AR by regulating microbiota dysbiosis. Methods: The ovalbumin-induced mouse AR model was used to evaluate the therapeutic effect of MFXD on AR. Then 16S rDNA amplicon sequencing, untargeted metabolomics, and other molecular biology technology were used to clarify the effects of MFXD on lung microbes dysbiosis and AR progression. Further, the human nasal epithelial cell line (HNEpCs) was used to evaluate the protective effect of MFXD on epithelial barrier damage caused by specific pathogens. Results: MFXD decreased plasma histamine and IgE levels, ameliorated pathological damage, and diminished the expression of tight junction proteins (ZO-1 and occludin) in lung and nasal tissues. MFXD altered AR-induced microbiota dysbiosis in the lungs and also plasma metabolites. Oral administration of MFXD altered microbiota dysbiosis in lung and AR-associated metabolic disorders. The dominant bacteria in the lungs of AR mice damaged the airway barrier, and MFXD reversed this change. Conclusion: This study revealed the correlation between the lung microbiota and AR in the mice model. We confirmed that lung microbiota plays a vital role in AR and that MFXD reduced damage to the epithelial barrier of the lungs and nasal mucosa by regulating lung microbiota and plasma metabolism imbalances. Our research provides a reference for the effect of lung microbiota on AR and provides a new idea for the treatment of AR.

PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies. Methods: We analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases. Results: The HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance. Conclusion: This study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.

A New HPLC-UV Method Using Hydrolyzation with Sodium Hydroxide for Quantitation of Trans-p-Hydroxycinnamic Acid and Total Trans-p-Hydroxycinnamic Acid Esters in the Leaves of Ligustrum robustum.

Trans-p-hydroxycinnamic acid and its esters in the leaves of Ligustrum robustum might be a new resource to prevent diabetes and its complications. In the present study, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in the leaves of L. robustum was developed, since it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. The extract of L. robustum was hydrolyzed with sodium hydroxide at 80 °C for 2 h, and then, hydrochloride was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL·min-1 and detecting at 310 nm. The linear range for trans-p-hydroxycinnamic acid was 11.0-352.0 µg·mL-1 (r2 = 1.000). The limit of detection and limit of quantification were 2.00 and 6.07 µg·mL-1, respectively. The relative standard deviations of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 103.3% ± 1.1%. It is the first HPLC method using hydrolyzation for quantification of many carboxylic esters. Finally, the method was used successfully to determine trans-p-hydroxycinnamic acid and total trans-p-hydroxycinnamic acid esters in various extracts of the leaves of L. robustum. The 60-70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96-3.99 mg·g-1), and the 50-80% ethanol extracts of L. robustum displayed the highest contents of total trans-p-hydroxycinnamic acid esters (202.6-210.6 mg·g-1). The method can be applied also to the quality control of the products of L. robustum.

Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study.

BACKGROUND: Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. METHODS: This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma who had not previously received any systemic treatment were randomly assigned (1:1) to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Randomisation was done via a centralised interactive response system. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. We report the findings from the prespecified primary analysis for progression-free survival and interim analysis for overall survival. This study is registered with ClinicalTrials.gov (NCT03764293). FINDINGS: Between June 28, 2019, and March 24, 2021, 543 patients were randomly assigned to the camrelizumab-rivoceranib (n=272) or sorafenib (n=271) group. At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7·8 months (IQR 4·1-10·6). Median progression-free survival was significantly improved with camrelizumab-rivoceranib versus sorafenib (5·6 months [95% CI 5·5-6·3] vs 3·7 months [2·8-3·7]; hazard ratio [HR] 0·52 [95% CI 0·41-0·65]; one-sided p<0·0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14·5 months (IQR 9·1-18·7). Median overall survival was significantly extended with camrelizumab-rivoceranib versus sorafenib (22·1 months [95% CI 19·1-27·2] vs 15·2 months [13·0-18·5]; HR 0·62 [95% CI 0·49-0·80]; one-sided p<0·0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab-rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab-rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse). INTERPRETATION: Camrelizumab plus rivoceranib showed a statistically significant and clinically meaningful benefit in progression-free survival and overall survival compared with sorafenib for patients with unresectable hepatocellular carcinoma, presenting as a new and effective first-line treatment option for this population. FUNDING: Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.