ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

This article systematically analyzed the historical evolution of the name， origin， harvesting and others of Longan Arillus by referring to the ancient and modern literature， in order to provide a foundation for developing famous classical formulas containing this herb. After textual research， it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties， Longan Arillus gradually replaced longan as the standard name recorded in the materia medica， with additional aliases including Yizhi， Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian， Guangdong， Guangxi， Hainan， Sichuan and others. Since the Qing dynasty， Longan Arillus produced in Fujian， Guangdong and Guangxi have been regarded as the finest and authentic varieties， with Fujian， Guangxi， and Guangdong remaining the primary authentic production areas today. In ancient times， the fruits were primarily harvested in August of the lunar calendar. However， modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history， processing methods have primarily focused on raw product， though techniques such as wine soaking and powdering have also been employed. Since modern times， it has been concluded that its quality is the best one with thick flesh， sweet taste， brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature， entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen， nourishing the blood and calming the spirit， which is consistent in ancient and modern times. Based on the textual research， it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements， where no specific processing is indicated， the raw products is recommended for medicinal use.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Objective:The aim of this study is to investigate the main active substances of Qilin pills by high performance liq-uid chromatogre-electrostatic field orbitrap mass spectrometry(HPLC-Q-Orbitrap/MS),and explore the mechanism of its action in the treatment of asthenozoospermia by combining network pharmacology and molecular docking.Methods:(1)Qilin pills were quantita-tively and qualitatively analyzed by HPLC-Q-Orbitrap/MS.(2)The top 100 compounds in Qilin pills were screened by content analy-sis and SwissADME,and their targets were predicted.The asthenozoospermia targets were searched through the database.And a"pro-tein-protein interaction"(PPI)network was constructed.KEGG and GO analysis was performed using the DAVID database.And a"drug-target-pathway"network was constructed.(3)SailVina was used for molecular docking.Results:(1)A total of 1 275 known components were found and ranked in Qilin pills by HPLC-Q-Orbitrap/MS analysis.(2)The top 100 compounds in Qilin pills predicted a total of 1 053 targets and 184 potential therapeutic targets for asthenozoospermia.KEGG pathway analysis and GO analysis showed that the treatment of asthenozoospermia by Qilin pills may be related to the steroid hormone synthesis pathway,the response to steroid hormones,the chromosomal region of cells and the activity of steroid hydroxylase.The mechanism of Qilin pills in treating as-thenozoospermia may be related to regulating the synthesis,metabolism and reaction process of sex hormone in the body.(3)The mo-lecular docking results of its key targets(CYP19A1,ESR1,HSP90AA1,p53,HIF1α and BCL2)showed that the key active ingredi-ents M030,M039,M043,M050,M055 and M073 of Qilin pills had spontaneous binding.It had a binding energy of less than-5 kJ/mol.Conclusion:The material basis of Qilin pills has been explored by this study.And the mechanism of action of Qilin pills in the treatment of asthenozoospermia is highly bound to the expression and response process of steroid hormones,which provides a theoretical basis for the clinical application of Qilin pills.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.