With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective To observe the effect of ultrasound-guided iliopsoas plane block(IPB)on the quality of postoperative recovery in patients undergoing hip arthroplasty.Methods Sixty patients who underwent hip arthroplasty were selected,37 males and 23 females,aged 40-79 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ.The patients were divided into two groups by random number table method:the iliopsoas plane block group(group IPB)and the femoral nerve block(FNB)group(group FNB),30 pa-tients in each group.Before anesthesia induction,IPB was performed with 0.5%ropivacaine 10 ml and lat-eral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group IPB.And FNB was performed with 0.5%ropivacaine 10 ml and lateral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group FNB.The dosages of propofol,remifentanil,and cis-atracurium during operation were recorded.The quality of recovery-15(QoR-15)scale was evaluated preoperatively and postoperatively 1 day,2 and 3 days.The max VAS(VASmax)pain score and manual muscle test(MMT)score of quadri-ceps muscle were recorded 12,24,and 48 hours after surgery.The time of getting out of bed for the first time,opioid dosage,and patient satisfaction were recorded.The incidence of nerve injury,vascular injury,puncture site infection,and local anesthetic poisoning were recorded.The postoperative complications of diz-ziness,nausea and vomiting,deep vein thromboses,and elirium were also recorded.Results There was no significant difference in the dosage of propofol,remifentanil,and cis-atracurium between the two groups.Compared with group FNB,the QoR-15 scale score in group IPB was significantly higher 1 day,2 and 3 days after operation(P＜0.05).Compared with group FNB,the MMT scores of quadriceps muscle was sig-nificantly higher in group IPB 12 and 24 hours after surgery(P＜0.05),and the first time of getting out of bed was shortened in group IPB(P＜0.05).However,there were no significant differences in the VASmax pain score,MMT score of quadriceps muscle 48 hours after surgery,opioid dosage,and patient satisfaction between the two groups.No nerve block related complications were found in both groups.There were no sig-nificant differences in postoperative complications between the two groups.Conclusion The iliopsoas plane block can improve the quality of postoperative recovery and accelerate the recovery of patients with hip re-placement,and the effect is better than that of femoral nerve block.

Podophyllotoxin is an aryl naphthalene lignan-like secondary metabolite, which is widely existed in plants of the Podophyllum. It exhibits a broad spectrum of antitumor activity and holds significant clinical value as a medicinal natural product of plant origin. This review discusses podophyllotoxin from three aspects: plant distribution, biosynthesis and pharmacological effects. Distribution of podophyllotoxin in nature: Podophyllotoxin and its analogues are mainly found in 12 genera of three families, which are Berberidaceae, Linaceae and Cupressaceae, respectively. They are mostly distributed in East Asia and North America, especially in China, which is not only the diversity center of the Podophyllum, but also the distribution center. Among all these plants, the genera Dysosma and Sinopodophyllum are the focus of the relevant research. Biosynthesis of podophyllotoxin: In order to take the alleviation of the pressure of podophyllotoxin that is in short supply of natural resources, and to protect its existing resources, the biosynthesis of podophyllotoxin, especially synthetic biology, has gradually become a new direction of current research. Compared with chemical synthesis which has the shortcoming of low synthesis efficiency, high production cost and cumbersome steps, biosynthesis has a variety of advantages. It’s not limited by resources, easy to cultivate on a large scale and has fast production speed, low production cost and simple genetic manipulation, so there is a broader prospect for the exact purpose of biosynthetic development. The biosynthesis of podophyllotoxin is divided into four steps in general, including the synthesis of coniferyl alcohol, the synthesis of matairesinol, the synthesis of deoxypodophyllotoxin and the synthesis of podophyllotoxin. It requires various enzymes catalyzed during the synthesis process, such as pinoresinol-lariciresinol reductase(PLR), secoisolariciresinol dehydrogenase(SDH) and others. At present, by means of synthetic biology, heterologous production of natural drugs in microbial cell factories, the synthesis of the intermediate coniferyl alcohol has been achieved in Escherichia coli with an increased yield of (124.9±5.1)mg·L−1, and the concentration of (-)-pluviatolide was elevated to 137 mg·L−1. In addition, p-coumaric acid in Saccharomyces cerevisiae was obtained to 71.71 mg·L−1, and in a tobacco plant production chassis, highly purified (-)-deoxypodophyllotoxin was increased to 0.71 mg·g−1 (dry weight) after chromatographic separation. Overall, the utilization of biosynthesis can significantly increase the yield of podophyllotoxin and improve the research and production efficiency of anti-tumor drugs greatly, which brings a more effective strategy for the treatment of related diseases. The pharmacological activity of podophyllotoxin: Podophyllotoxin and its analogues have strong cytotoxicity and they exert good inhibitory effects on the proliferation of multifarious tumor cells, viruses and bacteria. So they are widely applied to the clinical treatment of various types of tumors, such as colorectal cancer, lung cancer, cervical cancer, hemangioma, breast cancer, esophageal cancer, etc. The molecular mechanism of its cancer treatment is mainly in the G1, G2/M to block the cell cycle to make drugs work. Meanwhile, podophyllotoxin has relatively significant toxic side effects and drawbacks that can’t be ignored as a drug with superior therapeutic effect on specific diseases, which tends to increase the risk of bone marrow suppression, chromosomal aberrations and so forth. In conclusion, this literature sums up the distribution of podophyll plants in China, making review of the biosynthetic steps, applications, and biological research of podophyllotoxin, and outlines the pharmacological activity of podophyllotoxin. It aims to set the foundation for the reasonable application of podophyllotoxin resources, the efficient synthesis of podophyllotoxin, and the development of Podophyllum drugs which are highly effective and low toxic. At the same time, this paper gives full play to the clinical medicinal value of podophyllotoxin, which has important influence and far-reaching significance in the treatment of malignant diseases, and promotes the modernization of traditional Chinese medicine.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Although geriatric diseases are complicated due to the coexistence of many diseases,they often have a common pathological basis and are closely related to the pathogenesis of deficiency and excess in traditional Chinese medicine.Exploring the characteristics of the pathogenesis of deficiency and excess diseases in the elderly is helpful to keep simplicity and restrain complexity,grasp the law of occurrence and development of diseases in the elderly as a whole,and give full play to the advantages of traditional Chinese medicine in the prevention and treatment of chronic diseases.Based on the fundamental characteristics of deficiency and excess in senile diseases,researcher Hu Jingqing further summarized that"essence deficiency,Yin deficiency,Yang deficiency,qi deficiency,blood deficiency"and"qi stagnation,phlegm dampness,blood stasis,fire and heat,and latent wind"are the most common pathogenesis in the occurrence and development of senile diseases.Among them,deficiency is the basic pathogenesis of senile diseases,especially deficiency of kidney essence.Excess disease is the key pathogenesis of the development and changes of senile diseases.Qi stagnation is often the initial step in the development of senile diseases.Phlegm dampness and blood stasis are the pathological products of"excess due to deficiency"and are also the main secondary pathogenesis of senile diseases.In clinical identification of senile diseases,attention should be paid to grasping the pathogenesis of deficiency and excess and its concurrent changes.

Lactic acid bacteria(LAB)were isolated and cultivated from the intestinal contents of rabbits by MRS-CaCO3 solid medium.Identification was achieved through morphological observa-tion,Gram staining,physiological and biochemical characterisation,16S rDNA sequence analysis,and ERIC-PCR analysis.Strains displaying typical Lactobacilli characteristics were exanimated for their biological characteristics,resistance properties,adherence capacity in vitro,colonization abili-ty in vivo,and safety profile.In this study,a total of four strains of Lactobacillus reuteri were iso-lated from rabbits,all of which exhibited typical biological characteristics of LAB.These strains demonstrated inhibitory effects on common pathogenic bacteria in the gastrointestinal tract,with the primary inhibitory substance being bacteriocin.Furthermore,they showed sensitivity to chlor-amphenicol,rifampicin,and erythromycin,and displayed a degree of tolerance to gastrointestinal conditions and high temperature.These stains were capable of successful colonization in rabbits with a higher degree of safety.This study lays a foundation for the development of LAB prepara-tions for the prevention and treatment of rabbit intestinal diseases.

Objective:To compare the efficacy and safety of stone extraction with a single peroral choledochoscopy system under direct visualization and conventional X-ray endoscopic retrograde cholangiopancreatography (ERCP) for non-difficult common bile duct stones.Methods:A total of 164 patients with common bile duct stones who underwent stone extraction by using the single peroral choledochoscopy system under direct visualization (the observation group, n=82) and conventional X-ray endoscopic retrograde cholangiopancreatography (ERCP) (the control group, n=82) from January 2018 to April 2022 in Dongfang Hospital, Beijing University of Chinese Medicine were enrolled. The observation group was directly selected from the database, while the control group was randomly matched by age stratification with baseline data validated. The success rates of intubation, stone removal, postoperative complication incidence, and radiation exposure between the two groups were compared. Results:There was no significant difference between the baseline data of the observation group and the control group ( P>0.05). The number of patients with detected stones≥2 in the observation group and the control group were 59 (71.95%) and 37 (45.12%) respectively with significant difference ( χ 2=12.16, P=0.001). The success rates of bile duct intubation in the observation group and the control group were both 100.00% (82/82). The success rates of stone extraction were 98.78% (81/82) and 100.00% (82/82) respectively with no significant difference ( P>0.05). The one-time stone removal rates of the two groups were 93.90% (77/82) and 92.68% (76/82) respectively with no significant difference ( χ2=0.10, P=0.755). There was no significant difference in the incidence of postoperative complications between the observation group and the control group ( P>0.05). The amount of intraoperative ray exposure volume in the observation group was significantly lower than that of the control group [10.20 (6.69, 18.94) mGy VS 15.41 (10.70, 22.77) mGy, U=2 462.00, P=0.003]. Conclusion:The efficacy and safety of stone extraction with single peroral choledochoscopy system under direct visualization are comparable to those of traditional X-ray ERCP for non-difficult common bile duct stones, but it can significantly reduce the intraoperative ray exposure volume during therapeutic ERCP stone extraction.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To investigate the effects of 30% ethanol elution fraction of Artemisia absinthium extract with macroporous resin (AAEM-30%) on the dendritic cell (DC) and immunity of mice. Methods:AAEM-30% was obtained from the alcoholic extracts of A. absinthium by AB-8 macroporous resin, and its polysaccharide, flavonoid, and terpenoid contents were determined. The expressions of AAEM-30% on DC surface molecular cluster of differentiation (CD) 40, CD80 and CD86 were detected in vitro by flow cytometry, and the expressions of DC cytokines IL-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The effect of AAEM-30% on the immune function of ICR mice was measured in vivo with different doses (50 and 100 mg/kg) and different administration methods (subcutaneous injection, intraperitoneal injection, and gavage). Results:The contents of polysaccharides, flavonoids, and terpenoids in AAEM-30% were 24.30%, 22.50% and 28.19%, respectively. AAEM-30% significantly enhanced the expression of CD40, and CD86 and the secretion of IL-6 and TNF-α (all P<0.001). Compared with the control group, no statistically significant differences were found in the body mass of mice compared with the three administration methods (all P>0.05). The thymus index in the 50 and 100 mg/kg AAEM-30% intraperitoneal injection groups and the spleen index in the 50 mg/kg AAEM-30% gavage group were increased (all P<0.05). CD19 + cells increased in the 100 mg/kg AAEM-30% intraperitoneal injection group ( P<0.01) and in the 50 mg/kg AAEM-30% gavage group ( P<0.05). The CD11b + and CD11c + counts increased in the 100 mg/kg AAEM-30% gavage group ( P<0.05). The number of CD4 + and CD8 + T lymphocytes was increased by both gavage and intraperitoneal administration (all P<0.05). Conclusions:AAEM-30% can promote the maturation of DC and enhanced the immunity of mice without obvious side effects.