Consensus method is not only a common technical approach to the formulation of the acupuncture-moxibustion guidelines, but also an important way to form the recommended treatment protocols of acupuncture-moxibustion guidelines. Based on the theory of implementation science, the paper explores the influencing factors of consensus-reaching to acupuncture-moxibustion guidelines, and puts forward methodological suggestions on the consensus method performed in the formulation of acupuncture-moxibustion guidelines, so as to advance the rational application of consensus method and enhance the scientificity and transparency of acupuncture-moxibustion guidelines.
Moxibustion/standards* ; Humans ; Acupuncture Therapy/standards* ; Consensus ; Practice Guidelines as Topic

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

OBJECTIVE: The investigation of the correlation between ecological factors and the genetic characteristics or metabolites of plants offers valuable insights into the regional causes of genetic and metabolic diversity. Here, Gastrodia elata, a medicinal plant, is employed as a model to explore the environmental factors that influence its genetic characteristics and metabolic accumulations. METHODS: A total of 23 G. elata populations from six cultispecies and 11 cultivated regions were selected based on the predictions of the global geographic information system. The genetic characteristics of these populations were evaluated using highly polymorphic simple sequence repeat markers. Additionally, the metabolic accumulations and antioxidant capacity of mature tubers were measured employing colorimetry and high performance liquid chromatography (HPLC). Ecological data of each region were obtained from the WorldClim-global climate database and harmonized world soil database. To assess the influence of ecological factors on the genetic characteristics and metabolic profiles of G. elata, Pearson's correlation analysis was conducted. RESULTS: Genetic variation among G. elata populations exceeded that within populations. Genetic diverisity, distance and structure manifested regional and species-specific patterns. Metabolic profiling and antioxidant capacity exhibited regional variations. Notably, the Lueyang region demonstrated that a content range of total polysaccharide, total protein, and phenolic glycosides was 9.34%-189.67% higher than the average. Similarly, in the Hubei region, total phenolic content, p-hydroxybenzyl alcohol content, and antioxidant indicators were observed to be higher than the average levels, by 106.57%, 136.47% and 12.50%-91.14%, respectively. Furthermore, ecological factors had a significant comprehensive impact on G. elata genetic characteristics (r > 0.256 and P < 0.05). Multivariate metabolite accumulations in G. elata were influenced by dominant ecological factors. Temperature notably impacted the accumulation of total protein (|r| > 0.528 and P < 0.05). Moisture, encompassing precipitation and soil content, significantly affected the production of phenolic glycosides (|r| > 0.503 and P < 0.05). CONCLUSION The genetic characteristics of G. elata manifested regional and species-specific patterns, with the metabolic accumulations and antioxidant capacity of mature tubers exhibited regional variations. Specifically, multivariate ecological factors comprehensively influenced genetic characteristics. Temperature and moisture played pivotal roles in regulating the accumulations of proteins and phenolic glycosides, respectively. These findings underscore the significant impact of ecological factors on the shaping of G. elata, highlighting their crucial role in enhancing the quality of Chinese medicinal materials.

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

BACKGROUND:Bushen Yiqi Huayu granule has the effect of replenishing qi and eliminating blood stasis,tonifying kidney and smoothing collages,and is often used in the treatment of osteoporosis.At present,there are few studies on the effect of Bushen Yiqi Huayu granule on the callus angiogenesis of osteoporotic fractures. OBJECTIVE:To explore the mechanism of Bushen Yiqi Huayu granule by up-regulating extracellular signal-regulated kinase/mitogen-activated protein kinases(ERK/MAPK)signaling pathway to improve callus angiogenesis after fracturing in osteoporotic rats. METHODS:(1)Bone marrow mesenchymal stem cells from osteoporotic SD rats and bone marrow monocytes from C57BL/6 mice were collected.MTT assay was used to detect different doses of Bushen Yiqi Huayu granule on bone mesenchymal stem cell toxicity.Bone mesenchymal stem cells and bone marrow monocytes were cultured in the medium supplemented with 0 and 1.5 mg/mL Bushen Yiqi Huayu granules,respectively,and osteogenic differentiation and osteoclast differentiation were carried out in vitro.(2)144 SD rats were randomly divided into sham operation group,model group,granule group and granule+PD98059 group with 36 rats in each group.The osteoporotic model was established in the model group,granule group and granule+PD98059 group,and only part of the adipose tissue near the ovary was removed in the sham operation group.8 weeks later,all rats received left tibial osteotomy.In the granule+PD98059 group,5 g/kg Bushen Yiqi Huayu granule was given intragastrically,and 0.3 mg/kg PD98059 was injected into the tail vein.The granule group was given 5 g/kg Bushen Yiqi Huayu granule,and the same volume of normal saline was injected into the tail vein.The sham operation group and model group were given an equal volume of normal saline,and the caudal vein was injected with an equal volume of normal saline.Drug administration was conducted once a day for 8 weeks.Fracture healing and callus angiogenesis were observed by X-ray,micro-computed tomography and microvascular perfusion angiography.Bone mineral density and mechanical strength of the callus were measured.The tibia was observed by hematoxylin-eosin staining and Masson staining.Western blot assay and immunohistochemistry were used to examine the expression of ERK/MAPK signaling pathway-related molecules. RESULTS AND CONCLUSION:(1)Compared with the 0 mg/mL group,the alkaline phosphatase activity,mineralization level,p-ERK1/2 and p-p38 MAPK expression levels of osteocytes increased(P<0.05),while the density and volume of osteoclasts decreased in the 1.5 mg/mL group(P<0.05).(2)Compared with the sham operation group,the fracture healing degree of the granule group was similar at 4 and 8 weeks,but there was no significant difference in Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,spacing,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels(P>0.05).In the model group and granule+PD98059 group,fracture healing was slow,Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels decreased(P<0.05),and vascular spacing increased(P<0.05),compared with the sham operation group.(3)It is indicated that Bushen Yiqi Huayu granule can improve fracture healing,promote callus angiogenesis and alleviate the symptoms of osteoporosis by enhancing the expression of the ERK/MAPK signaling pathway-related molecules in osteoporotic rats.

Objective To explore the effect and potential mechanisms of melatonin combined with gemcitabine on the chemosensitivity of human pancreatic cancer cell line PANC-1.Methods Human pancreatic cancer cell line PANC-1 was trea-ted with gemcitabine alone or in combination with melatonin.Cell viability was assessed using CCK-8.Effect of melatonin and gem-citabine alone or in combination on the clonogenic capacity of PANC-1 cells were observed through colony formation experiments.Scratch assays and transwell experiments were conducted to evaluate cell migration ability.Reactive oxygen species(ROS)and mitochondrial membrane point JC-1 assay kit were used to determine reactive oxygen species synthesis and membrane potential levels.Intracellular Fe2+level was measured using ferrous ion fluorescent probe.The protein expression levels of LC3,P62,GPX4 and SLC7A11 in different treatment groups were detected by immunofluorescence and Western blotting.Results CCK-8 results showed that the viability of PANC-1 cells was inhibited by gemcitabine alone after 48 h and 72 h of treatment in a time-and dose-dependent manner.The cell viability of gemcitabine combined with melatonin group was significantly lower than that of gemcitabine group,and the cell viability decreased with the increase of melatonin concentration.Scratch assays,transwell experiments,and plate colony formation assay results demonstrated that the proliferation and migration of cells in the gemcitabine combined with the me-latonin group were significantly inhibited compared with the gemcitabine group.The levels of reactive oxygen species and Fe2+in PANC-1 in gemcitabine combined with the melatonin group were higher than those in the gemcitabine group,and the mitochondri-al membrane potential was significantly decreased(P＜0.01).Western blotting and immunofluorescence results showed that the ra-tio of autophagy-related protein LC3-Ⅱ/LC3-Ⅰ in gemcitabine combined with the melatonin group was lower than that in the gem-citabine group,and the expression of P62 was up-regulated,and the expression of anti-iron death-related protein GPX4 and SLC7A11 was significantly inhibited(P＜0.05),suggesting that melatonin combined with gemcitabine can inhibit autophagy and promote ferroptosis in PANC-1 cells.Conclusion Melatonin enhances the chemosensitivity of pancreatic cancer cell PANC-1 to gemcitabine by inhibiting autophagy and promoting ferroptosis of tumor cells.

Objective To investigate the distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Lüliang City, Shanxi Province, so as to provide insights into assessment of the visceral leishmaniasis transmission risk and formulation of visceral leishmaniasis control measures. Methods A total of 12 natural villages were sampled from Shilou County, Lishi District, Lanxian County, Linxian County and Wenshui County in Lüliang City, Shanxi Province from June to September, 2023, and sandflies were captured using light traps from 7 breeding habitats, including farmers’ houses, sheep pens, cattle pens, chicken coops, pig pens, mule and horse pens, and loess-cave dwellings. Following morphological identification of the sandfly species, the distribution of sandflies and the seasonal fluctuations of the sandfly density were analyzed. In addition, the Leishmania was detected in sandflies using a real-time fluorescence quantitative PCR assay. Results A total of 2 831 sandflies were captured with 156 light traps in Lüliang City from June to September, 2023, including 2 638 female sandflies (93.18%) and 193 male sandflies (6.82%), and the average density was 16.91 sandflies/(light-night). The seasonal fluctuations of the sandfly density all appeared a unimodal distribution in all survey sites, and the sandfly density peaked in July and then declined rapidly. Among all types of breeding habitats, the greatest sandfly density was found in sheep pens [39.04 sandflies/(light-night)]. In addition, 4.08% (2/49) of the sandfly samples were tested positive for Leishmania nucleic acid as revealed by the real-time fluorescence quantitative PCR assay. Conclusions Sandflies were widely distributed in Lüliang City, Shanxi Province in 2023, and the peak of the sandfly density was observed in July, which had a visceral leishmaniasis transmission risk. Intensified surveillance of visceral leishmaniasis and sandfly vectors is required and targeted vector control is recommended.

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.