Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

Heart failure(HF) is the terminal stage of various cardiovascular diseases, characterized by high morbidity and mortality, and it represents one of the major disease burdens for families and society. In recent years, as research on the molecular mechanisms of HF has deepened, a competing endogenous RNA(ceRNA) network mediated by long non-coding RNAs(lncRNAs) and circular RNAs(circRNAs) has been gradually constructed. Extensive research results have confirmed that the ceRNA network is widely involved in pathological processes such as inflammation, oxidative stress, myocardial hypertrophy, apoptosis, remodeling of extracellular matrix components and structure, and ferroptosis in HF. It reveals the complex pathological mechanisms of HF at the epigenetic level. Traditional Chinese medicine(TCM) plays a unique role in improving symptoms and prognosis of HF and intervenes in the ceRNA network in HF through multi-level and multi-target mechanisms. It improves key pathological processes such as myocardial fibrosis and inflammation, making progress in treating HF at the molecular level. This article summarized recent Chinese and international research on the regulatory mechanisms of ceRNA networks in HF, elaborated on the mechanisms of action of ceRNA networks in different pathological stages of HF, and summarized how effective components and compounds of TCM intervene in the ceRNA network to improve HF, so as to refine the molecular mechanisms of HF and provide directions for more precise molecular targeted therapeutic strategies.
Humans ; Heart Failure/metabolism* ; Medicine, Chinese Traditional ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Circular/genetics* ; RNA, Long Noncoding/metabolism* ; Gene Regulatory Networks/drug effects* ; RNA/metabolism* ; RNA, Competitive Endogenous

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

OBJECTIVE: To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele（VC）with male infertility. METHODS: A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis. The patients were divided into the microscopic group (180 cases) and laparoscopic group (127 cases) according to the surgery method. The pre- and postoperative clinical data of these two groups were analyzed, including the degree of dilatation and reflux time of internal spermatic vein，hemodynamic parameters of testicular capsular artery，proportion of progressive motility spermatozoa (PR), concentration of spermatozoa, proportion of normal morphology sperm，the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively. RESULTS: All the surgeries for the 307 patients in this study were successful. There was no significant difference in operation time, hospitalization time and management expenses between the microscopic group and the laparoscopic group (P>0.05). Compared to the patients in laparoscopic group, the patients in the microscopic group received a better improvement in venous diameter, reflux time of spermatic veins and hemodynamic parameters of testicular capsular artery (P<0.05). Moreover, the semen analysis showed that the PR, spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group (P<0.05). During the 2-year follow-up period, the conception rate of spouses in the microscopic group was 67.2%, while only 47.2% in the laparoscopic group, in which the difference was statistically significant (P<0.05). Besides, the time-to-pregnancy ( TTP ) within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group（P<0.05). Meanwhile, the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group (P<0.05). It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group (P<0.05). Severe complication such as testicular atrophy, bleeding and infection did not appear in both of two groups. However, the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group (P<0.05). CONCLUSION Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility. But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters, semen quality, pregnancy outcome and postoperative complications, which is worthy of further clinical applications.
Humans ; Male ; Varicocele/complications* ; Laparoscopy ; Infertility, Male/etiology* ; Retrospective Studies ; Adult ; Microsurgery ; Treatment Outcome ; Pregnancy ; Female

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Physiologically based pharmacokinetic (PBPK) models have been widely used to predict various stages of drug absorption, distribution, metabolism and excretion. Models based on machine learning (ML) and artificial intelligence (AI) can provide better ideas for the construction of PBPK models, which can accelerate the prediction speed and improve the prediction quality of PBPK. ML and AL can complement the advantages of PBPK model to accelerate the progress of drug research and development. This review introduces the application of machine learning and artificial intelligence in pharmacokinetics, summarizes the research progress of physiological pharmacokinetic models based on machine learning and artificial intelligence, and analyzes the limitations of machine learning and artificial intelligence applications and their application prospects and prospects.

Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).

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.