This paper summarizes Professor HAN Mingxiang's clinical experience in treating chronic obstructive pulmonary disease （COPD）. He believes that the key pathomechanism of COPD in the acute exacerbation stage is the invasion of external pathogens triggering latent illness， while lung qi deficiency is the primary mechanism in the stable stage. The core pathological factors throughout disease progression are deficiency， phlegm， and blood stasis. Treatment emphasizes a staged and syndrome-based approach. During the acute exacerbation stage， for wind-cold invading the lung syndrome， the self-formulated Sanzi Wenfei Decoction （三子温肺汤） is used to relieve the exterior， dispel cold， warm the lung， and resolve phlegm. For phlegm-dampness obstructing the lung syndrome， Huatan Jiangqi Fomulation （化痰降气方） is prescribed to warm the lung， transform phlegm， descend qi， and calm wheezing. For phlegm-heat obstructing the lung syndrome， Qingfei Huatan Fomulation （清肺化痰方） is applied to clear heat， resolve phlegm， moisten the lung， and stop coughing. For phlegm and blood stasis interlocking syndrome， Qibai Pingfei Fomulation （芪白平肺方） is used to tonify qi， resolve phlegm， and activate blood circulation to remove stasis. During the stable stage， for lung qi deficiency syndrome， Shenqi Wenfei Decoction （参芪温肺汤） is employed to warm the lung， tonify qi， resolve phlegm， and eliminate turbidity. For lung-spleen qi deficiency syndrome， Shenqi Buzhong Decoction （参芪补中汤） is utilized to strengthen the spleen， tonify qi， and reinforce metal （lung） from earth （spleen）. For lung-kidney deficiency syndrome， Shenqi Tiaoshen Fomulation （参芪调肾方） is prescribed to tonify the lung， warm yang， and regulate kidney function to calm wheezing. These strategies provide insights into the traditional Chinese medicine treatment of COPD.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

ObjectiveTo explore the possible mechanism of action of Lifei Xiaoji Pill （理肺消积丸， LXP） in the treatment of non small cell lung cancer based on the Warburg effect and the USP47/BACH1 pathway. MethodsFifty C57BL/6 mice were randomly divided into five groups， model group， LXP group， inhibitor group， LXP + inhibitor group， and cisplatin group， with 10 mice in each group. A lung cancer mouse model was established by subcutaneously injecting Lewis cells. On the next day， the model group mice were given 0.2 ml of saline by gavage daily， the LXP group given 240 mg/（kg·d） of LXP solution once a day by gavage， the inhibitor group intraperitoneally injected with P22077 at a dose of 10 mg/（kg·d） every day， the LXP + inhibitor group given both LXP by gavage and P22077 by intraperitoneal injection once a day， and the cisplatin group received 0.5 mg/（kg·d） cisplatin intraperitoneally every other day. All treatments lasted for 14 days. On the day after the last dose， tumor weight and volume were measured， tumor histopathology was examined by HE staining， apoptosis in tumor tissues was detected by TUNEL staining， and proliferation cell nuclear antigen （PCNA） protein levels were detected by immunohistochemistry. Warburg effect indicators， including glucose concentration， lactate content， and adenosine triphosphate （ATP） production in tumor tissues， were measured. Western Blot and qRT-PCR were used to detect the protein and mRNA expression levels of USP47， BACH1， hexokinase 2 （HK2）， and glyceraldehyde 3-phosphate dehydrogenase （GAPDH）. ResultsCompared with the model group， all drug intervention groups showed reduced tumor weight and volume， improved tumor pathology， decreased PCNA positive rate， increased apoptosis rate， and reduced expression levels of USP47， BACH1， and HK2 proteins and mRNA （P＜0.05 or P＜0.01）. Except for lactate content in the cisplatin group， the glucose concentration in tumor tissues of other drug intervention groups increased， while lactate content and ATP production decreased （P＜0.05 or P＜0.01）. Compared with the LXP group， the LXP + inhibitor group showed more significant improvements in these indicators （P＜0.05 or P＜0.01）. Compared with the cisplatin group， the LXP + inhibitor group had lower mRNA expression of HK2 and GAPDH， and lower protein levels of USP47 and HK2 （P＜0.05 or P＜0.01）. Compared with the inhibitor group， the cisplatin group had higher HK2 protein levels， while the LXP + inhibitor group showed lower mRNA expression of BACH1， HK2， and GAPDH （P＜0.05 or P＜0.01）. ConclusionLXP significantly inhibits tumor growth in lung cancer mice， and its mechanism of action may be related to inhibiting the Warburg effect via the USP47/BACH1 pathway.

The ocular fundus vasculature, serving as a critical window for monitoring disease progression, represents one of the primary targets of hypoxic injury. A growing body of evidence suggests associations between specific ocular vascular pathologies and sleep-disordered breathing. Obstructive sleep apnea(OSA)has been implicated in fundus lesions through its detrimental effects on the central retinal artery, retinal veins, retinal microvasculature, and choroidal vessels. Mechanistically, these effects are linked to OSA-induced intermittent hypoxia, which drives hemodynamic disturbances, oxidative stress, inflammatory responses, altered blood composition, endothelial dysfunction, and neuroendocrine/metabolic dysregulation. This review synthesizes current evidence on OSA-related retinal vascular injury and elucidates its mechanistic pathways. The goal is to identify sensitive and specific retinal vascular biomarkers to facilitate the early detection of OSA and its associated complications.

Aim To explore the mechanism of modified Wuzi Yanzong pill to reduce testicular toxicity of Tripterygium wilfordii by means of network pharmacolo-gy.Methods The effective chemical composition and target of modified Wuzi Yanzong Pill to reduce testicu-lar toxicity of Tripterygium wilfordii were analyzed by using multiple databases to understand the mechanism of action.Results The first five compounds of modi-fied Wuzi Yanzong pill are quercetin,sucrose,kaempferol,galactose and ellagic acid,respectively.The first five targets were TP53,SRC,EP300,MAPK3,STAT3;KEGG pathway enrichment analysis mainly concentrated in cancer pathway,lipid and atherosclero-sis,hepatitis B,apoptosis,diabetes complications AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and other signaling pathways.Conclusions The ac-tive components of modified Wuzi Yanzong pill can re-duce the testicular toxicity of Tripterygium wilfordii mainly by interfering with TP53,SRC,EP300,MAPK3,STAT3 and other targets,regulating apoptosis,PI3K-Akt signaling pathway,diabetes complications AGE-RAGE signaling pathway,lipid metabolism and other pathways.

Objective To explore the analgesic effect of ultrasound-guided quadratus lumborum block at lateral supra-arcuate ligament after open hepatectomy.Methods A total of 106 patients with open hepatectomy in our hospital from April 2022 to May 2023 were selected prospectively and randomly divided into the control group(anesthetized by ultrasound-guided subcostal transverse abdominis plane block)and the observation group(anesthetized by ultrasound-guided quadratus lumborum block at lateral supra-arcuate ligament),with 53 cases in each group.The postoperative recovery index,immune function,and numerical rating scale(NRS)score and Ramsay sedation score in each time point of patients in the two groups were compared,and the incidence of adverse reactions during hospitalization was counted.Results The time of getting out of bed and anal discharge time of patients in the observation group were earlier than those in the control group(P<0.05),the dosage of sufentanil in 48 hours and numbers of analgesic pump compressions were less than those in the control group(P<0.05),Ramsay sedation scores 6 hours and 12 hours after surgery were higher than those in the control group(P<0.05),NRS scores at resting and cough 6 hours,12 hours,24 hours after surgery were lower than those in the control groups(P<0.05),the contents of CD4+,NK and CD4+/CD8+24 hours after surgery were higher than those in the control group(P<0.05).There was no statistically significant difference in the incidence of postoperative adverse reactions between the two groups(P>0.05).Conclusion Ultrasound-guided quadratus lumborum block at lateral supra-arcuate ligament in patients with open hepatectomy can achieve ideal analgesic and sedative effects,and promote postoperative recovery.

Objective:To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM)with mSMART 3.0 score.Methods:Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023,all of whom received daltezumab-based regimen(regimen drugs including dexamethasone,isazomib,bortezomib,lenalidomide).The efficacy and safety of the treatment were retrospectively analyzed.Results:The median age of 16 patients was 63.5(47-70)years old,including 10 cases of IgG type,2 cases of IgA type,and 4 cases of light chain type.The curative efficacy was judged in all 16 patients,with an overall response rate of 93.75％(15/16),including 4 cases of strict complete remission(sCR),1 case of complete remission(CR),2 case of very good partial remission(VGPR),partial remission(PR)in 5 cases,and minor remission(MR)in 3 cases.The median follow-up time was 11(2-30)months,and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period.The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia,and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections.Conclusion:Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

AIM To establish the HPLC fingerprints for freeze-dried powder of Yinhuo Decoction,and to determine the contents of rehmannitin D,methylophiopogonanone A,verbascoside,protocatechuic acid,catalpol,schisandrol A,schisandrin B,schisandrin A.METHODS The fingerprint esablishment was performed on a 30℃thermostatic Supersil AQ18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 230 nm.The UPLC-MS/MS content determination was performed on a 30℃thermostatic Alphasil VC-C18 column(2.1 mm×100 mm,2.5 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS There were 17 common peaks in the fingerprints for 10 batches of freeze-dried powder with the similarities of more than 0.90.and piloside,crystal blue glycoside,deacetylated caryoside schisandrin A were identified.Eight constituents showed good linear relationships within their own ranges(R2＞0.990 6),whose average recoveries were 98.7%-101.1%with the RSDs of 2.0%-5.2%.CONCLUSION The combination of fingerprints and content determination can completely characterize the quality of Yinhuo Decoction reference sample,thus provide a reference for the quality evaluation of its key chemical properties.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]