ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Medical artificial intelligence （AI） is a new type of application formed by the combination of machine learning， computer vision， natural language processing， and other technologies with clinical medical treatment. With the continuous iteration and development of relevant technologies， medical AI has shown great potential in improving the efficiency of diagnosis and treatment， and service quality， but it also increases the possibility of triggering ethical issues. Ethical issues resulting from the clinical application of medical AI were analyzed， including the lack of algorithmic interpretability and transparency of medical AI， leading to information asymmetry and cognitive discrepancies； the concerning status of security and privacy protection of medical data； and the complex and unclear division of responsibilities due to the collaborative participation of multiple subjects in the clinical application of medical AI， resulting in increased difficulty in the identification of medical accidents and clarification of responsibilities. The paper proposed the principles of not harming patients’ interests， physician’s subjectivity， fairness and inclusiveness， and rapid response. It also explored the strategies and implementation paths for responding to the ethical issues of medical AI from multiple perspectives， including standardizing the environment and processes， clarifying responsibility attribution， continuously assessing the impact of data protection， guaranteeing data security， ensuring model transparency and interpretability， carrying out multi-subject collaboration， as well as the principles of being driven by ethical values and adhering to the “human health-centeredness.” It aimed to provide guidance for the healthy development of medical AI， ensuring technological progress while effectively managing and mitigating accompanying ethical risks， thereby promoting the benign development of medical AI technology and better serving the healthcare industry and patients.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.

Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.

Objective To explore the protective effect and mechanism of Jinyinqingre oral liquid on acute lung injury in-duced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into six groups according to the random number table method:blank control group,model control group,Jinyinqingre oral liquid low-dose group,Jinyinqingre oral liquid medium-dose group,Jinyinqingre oral liquid high-dose group,and dexamethasone group.Except for the blank control group,the other groups were injected with lipopolysac charide(LPS)(5 mg·kg-1)into the trachea to establish the acute lung injury model of mice,and the Jinyinqingre oral liquid low,medium,and high groups were continuously administered the drug by gavage for three days.After 24 h,lung tissue and bronchoalveolar lavage fluid(BALF)were collected from the six groups for follow-up detection.The pathological injury of lung tissue in each group was observed by HE staining.The total number of cells in BALF was detected.The to-tal protein content of BALF was detected by the BCA method.The contents of inflammatory cytokines TNF-α,IL-1β,IL-6,and IgM in BALF were detected by ELISA.The expression of NF-κB and NLRP3 proteins in lung tissues was detected by immunohistochemistry and Western blotting.Results Compared with model control group,Jinyinqingre oral liquid alleviated the pathological injury of lung tissue(P＜0.05),decreased the total cell count,total protein content and IgM expression in BALF(P＜0.01),and the expres-sion of inflammatory cytokines TNF-α,IL-6 and IL-1β in BALF was dreased(P＜0.05),the protein expressions of NF-κB and NL-RP3 in lung tissues was dreased(P＜0.05).Conclusion Jinyinqingre oral liquid attenuated the pathological injury,inflammatory exudation,and expression of inflammatory cytokines in LPS-induced lung injury in mice,and its mechanism may be through the reg-ulation of NF-κB/NLRP3 signaling pathway,providing a theoretical basis for its clinical application.

OBJECTIVE To explore the correlation between changes in intestinal toxicity and changes in component composition of the Mongolian medicine Euphorbiae pekinensis Radix(EPR)before and after processing with milk.METHODS Mice were given 95%ethanol extract of raw EPR,milk-processed EPR and water-processed EPR by gavage.The purgative effect and intestinal inflam-matory toxicity changes of EPR before and after milk processing were investigated using the fecal water content and the levels of inflam-matory factors TNF-α and IL-1β in each intestinal segment of mice as indicators;LC-MS/MS was used to analyze the composition changes of the 95%alcohol extract of EPR before and after milk processing.RESULTS Compared with the blank group,the raw and water processed products of EPR could significantly increase the water content of mouse feces and the levels of TNF-α and IL-1β in each intestinal segment(P＜0.05);compared with the raw product group,all indicators in the milk processing group were significantly reduced(P＜0.05),while there was no significant difference in the water processing group,indicating that water processing cannot at-tenuate toxicity,and the auxiliary material milk is the key auxiliary material to reduce the toxicity of EPR.Mass spectrometry analysis results showed that a total of 50 components were identified in EPR,including 38 terpenoid components,6 phenolic acid components,and 6 other components.The content of each component decreased to varying degrees after milk processing.Principal component analy-sis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were performed on the mass spectrum data of raw ma-terials and products,and it was found that the components of raw materials and products can be obviously clustered into 2 categories.13 differential components of raw materials and products were screened through t test,and 11 of which were terpene compo-nents,indicating that the composition of terpene components changed significantly after milk processing.17 components derived from EPR were detected in the residual liquid of milk excipients after processing,of which 16 were terpenoids,indicating that the terpenoid components of EPR were transferred to the excipient milk during the soaking and processing processes.CONCLUSION The toxicity of EPR is reduced and the purgative effect is alleviated after milk processing.The attenuation mechanism may be that during the milk soaking and processing processes,terpenoid components are transferred to the milk,and the content of toxic components in the decoc-tion pieces is reduced,thereby reducing the toxicity.

Objective:To investigate the effect of Chinese medicine He's Yangchao recipe on premature ovarian insufficiency(POI)and its relationship with mitochondrial function of ovarian granulose cells in an animal model.Methods:Thirty-six female C57BL/6J mice were randomly divided into blank control group,model group,low-,medium-and high-dose He's Yangchao recipe treatment group and coenzyme Q10(Q10)treatment group(positive control).The POI model was induced by a single intraperitoneal injection of cyclophosphamide(90 mg/kg).The animals were sacrificed after 21 days.Primary granulose cells were obtained from POI mice and treated with He's Yangchao recipe,ERβ inhibitor PHTPP,and He's Yangchao recipe+PHTPP in vitro for 24 h,respectively.Ovarian histopathological changes were observed by hematoxylin-eosin(HE)staining,ATP levels were detected by luciferase assay,mtDNA copy numbers were detected by quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR),mitochondrial structure changes were observed by transmission electron microscopy,protein and mRNA expression levels of estrogen receptor β(ERβ),peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α),mitochondrial transcription factor A(TFAM),and superoxide dismutase 2(SOD2)were detected by Western blotting and qRT-PCR.Results:The ovarian tissue in model group exhibited few secondary and tertiary follicles,whereas the He's Yangchao recipe groups and Q10 group had abundant secondary and tertiary follicles.Compared with the blank control group,ATP and mtDNA levels in model group decreased(P＜0.01),mitochondrial crista disappeared or abnormal vacuolated structure increased;the protein and mRNA levels of ERβ,PGC1α,TFAM,and SOD2 decreased(all P＜0.01).ATP production increased in granulose cells of high-dose He's Yangchao recipe group and Q10 group;mtDNA copy numbers increased(P＜0.05 or P＜0.01);abnormal mitochondrial structure was reduced;the protein and mRNA expressions of ERβ,PGC1α,TFAM,and SOD2 increased(P＜0.05 or P＜0.01).Compared with the PHTPP intervention group,the proportion of normal mitochondrial structure in the granulose cells of He's Yangchao recipe+PHTPP group was higher;ATP content increased(P＜0.05 or P＜0.01);mtDNA copy numbers increased(P＜0.05 or P＜0.01);the protein and mRNA expression of ERβ,PGC1α,TFAM and SOD2 increased(P＜0.05 or P＜0.01).Conclusions:He's Yangchao recipe can regulate mitochondrial biogenesis through ERβ/PGC1α/TFAM pathway to improve ovarian function in POI mice.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Objective:To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA).Methods:This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged ( M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results:All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms.Conclusions:The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.