ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

Objective: To investigate the late identification and its influencing factors of newly reported HIV/AIDS cases in Linhai City, Zhejiang Province from 2015 to 2024, so as to provide a basis for formulating targeted AIDS prevention and control strategies. Methods: Data on newly reported HIV/AIDS cases in Linhai City from 2015 to 2024, including demographic characteristics and detection modes, were collected through the HIV/AIDS Comprehensive Control System of the Chinese Disease Prevention and Control Information System. The new identification rate and late identification proportion of HIV/AIDS cases were analyzed. The average annual percent change (AAPC) was used to assess trends in both the new identification rate and late identification proportion from 2015 to 2024. Multivariable logistic regression model was used to analyze the influencing factors for late identification among HIV/AIDS cases. Results: A total of 589 newly reported HIV/AIDS cases were documented in Linhai City from 2015 to 2024. The new identification rate declined from 5.08/105 in 2015 to 3.53/105 in 2024 (AAPC=-6.161%, P<0.05). Among them, 225 cases were late identified. After excluding 4 cases with inferred late identification, the late identification proportion increased from 24.53% in 2015 to 58.97% in 2024 (AAPC=7.595%, P<0.05). Multivariable logistic regression analysis indicated that age ≥25 years (25~<50 years, OR=3.569, 95%CI: 1.567-8.130; ≥50 years, OR=8.683, 95%CI: 3.440-21.917) and passive detection (OR=1.730, 95%CI: 1.022-2.928) were associated with a higher risk of late identification. In contrast, being married or having a spouse (OR=0.565, 95%CI: 0.332-0.960) was associated with a lower risk of late identification. Conclusions The new identification rate of HIV/AIDS cases in Linhai City from 2015 to 2024 showed a downward trend, while the proportion of late identification exhibited an upward trend. Age, marital status, and detection mode were identified as influencing factors for late identification among HIV/AIDS cases.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

ObjectiveTo analyze trends in the incidence and mortality of pancreatic cancer among the registered residents in Jinhua City of Zhejiang Province from 2016 to 2024, and to predict incidence and mortality rates from 2025 to 2027, thereby providing a reference for refining prevention and control strategies. MethodsData on pancreatic cancer incidence and mortality among the registered residents in Jinhua City from 2016 to 2024 were collected. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) to analyze the temporal trends of pancreatic cancer incidence and mortality. Furthermore, a GM (1,1) model was constructed using Excel 2019 to predict incidence rates and mortality rates for the years 2025 to 2027. ResultsFrom 2016 to 2024, the crude incidence and crude mortality rates of pancreatic cancer among the registered residents in Jinhua City were 8.41/100 000 and 8.19/100 000, respectively, both showing upward trends (AAPC=3.55%, 95%CI: 1.69%-5.63%; AAPC=3.35%, 95%CI: 1.08%-5.93%), while the standardized incidence and mortality rates were 5.21/100 000 and 4.93/100 000, respectively, with no statistically significant trends (AAPC=1.12% and 0.52%, both P>0.05). The incidence and mortality rates of pancreatic cancer were higher in men than in women. Both crude incidence and crude mortality rates rose steadily with increased age (both P<0.01). According to the GM (1,1) model, the crude mortality rate of pancreatic cancer among the registered residents in Jinhua City is projected to continue its upward trend from 2025 to 2027 (9.37/100 000, 9.60/100 000, and 9.83/100 000, respectively). ConclusionFrom 2016 to 2024, both the crude incidence and crude mortality rates of pancreatic cancer among registered residents in Jinhua City showed continuous upward trends, and the crude mortality rate is likely to continue rising from 2025 to 2027. Efforts to prevent and control pancreatic cancer should be strengthened, particularly among men and the very elderly.

ObjectiveTo explore the clinical efficacy of Juanbitang hot compress pack combined with intensive rehabilitation training in stroke patients with hemiplegia. MethodsA total of 80 stroke patients with hemiplegia were selected and assigned into a control group （40 cases） and an observation group （40 cases） according to the random number table method. The control group received conventional rehabilitation training and nursing intervention，while the observation group was additionally treated with Juanbitang hot compress pack. The two groups were compared in terms of the neurological function （national institute of health stroke scale score，NIHSS score），muscle strength，motor function （fugl-meyer assessment scale score，FMA score），daily living activity （modified barthel index，MBI），balance ability （berg balance scale score，BBS score），trunk control ability （Sheikh Trunk Control Test score，Sheikh TCT score），and homocysteine （Hcy） level before and after treatment. ResultsAfter treatment，the observation group had lower NIHSS score and Hcy level than the control group （P<0.05）. The total response rate of the observation group （97.50%） was higher than that of the control group （77.50%）. The scores of upper limb and lower limb FMA，MBI，BBS，and Sheikh TCT in the observation group were all higher than those in the control group （P<0.05）. ConclusionThe application of Juanbitang hot compress pack combined with rehabilitation training can effectively improve the neurological function，muscle strength，motor function，daily living ability，balance ability，and trunk control ability and reduce the Hcy level in stroke patients with hemiplegia，demonstrating enhanced clinical efficacy.

ObjectiveTo explore the latent profiles of sleep patterns and their association with gastrointestinal heat accumulation syndrome in preschool children in Beijing. MethodsA cross-sectional study design was adopted， and preschool children were recruited from 57 kindergartens in Beijing using convenience sampling. Sleep characteristics and gastrointestinal heat accumulation syndrome was assessed using the Chinese version of the Sleep Disturbance Scale for Children （SDSC） and Self-rating Diagnostic Scale for Gastrointestinal Heat Retention Syndrome in children （GHRS）. Latent profile analysis （LPA） was applied to identify distinct sleep-related subgroups， and multivariate logistic regression was used to analyze the association between different sleep profiles and gastrointestinal heat accumulation syndrome. ResultsA total of 6878 preschool children were included in the study. Among them， 3.46% of the children （238/6878） had sleep disorders， while 54.42% （3743/6878） had gastrointestinal heat accumulation. Compared to children without gastrointestinal heat accumulation syndrome， those with this syndrome exhibited a higher prevalence of sleep disorders， higher SDSC scores， higher T-transformed total scores， and higher scores across all dimensions， including disorders of initiating sleep， disorders of maintaining sleep， sleep hyperhidrosis， sleep breathing disorders， parasomnias， nonrestorative sleep and excessive somnolence （P＜0.01）. Latent profile analysis identified four distinct sleep characteristic profiles， which were the mixed high-symptom group （32.39%， 2228/6878）， sleep initiation and maintenance difficulty symptom group （49.07%， 3375/6878）， low-symptom group （14.19%， 976/6878）， and the group with no significant symptoms （4.35%， 299/6878）. Multivariate logistic regression analysis demonstrated that the mixed high-symptom group， sleep initiation and maintenance difficulty symptom group， and low-symptom group were significantly associated with gastrointestinal heat accumulation syndrome. Among them， the mixed high-symptom group had the most significant association with gastrointestinal heat accumulation （OR=12.657， P＜0.001）， followed by the sleep initiation and maintenance difficulty symptom group （OR=4.964， P＜0.001）. ConclusionSleep characteristics in preschool children mainly present as composite patterns with different symptom combinations. Moreover， the sleep latent profiles of the mixed high-symptom group， the sleep initiation and maintenance difficulty symptom group， and the low-symptom group were significantly associated with gastrointestinal heat accumulation syndrome.

OBJECTIVE To provide guidance for pharmaceutical care in patients with severe Cryptococcus gattii infections.METHODS Clinical pharmacists participated in the diagnosis and treatment of a male patient with disseminated Cryptococcus gattii infection （involving the lungs and central nervous system）. Given the patient’s poor response to initial therapy， the clinical pharmacists， based on antimicrobial susceptibility test results， recommended voriconazole as an alternative azole. In response to refractory hypokalemia caused by liposomal amphotericin B， the clinical pharmacists assisted the physician in developing an intensive potassium replacement regimen. Regarding the interaction between voriconazole and nifedipine， the clinical pharmacists proactively identified the risk and intensified monitoring of the patient’s blood pressure. In response to the onset of hepatitis C during treatment， the clinical pharmacists thoroughly weighed the priority of infection treatment and recommended temporarily postponing antiviral therapy for hepatitis C. For the individualized use of voriconazole， the clinical pharmacists repeatedly performed therapeutic drug monitoring （TDM）. Regarding the patient’s poor lesion resolution， the clinical pharmacists participated in multidisciplinary team discussions to clarify the indications for surgery.RESULTS The physician adopted the clinical pharmacists’ recommendations. Following pharmacological treatment and surgical intervention， the patient’s condition stabilized， and he was discharged while still on medication.CONCLUSIONS For severe Cryptococcus gattii infections， clinical pharmacists should focus on pathogen characteristics， strengthen adverse reaction management， pay close attention to drug interactions， conduct TDM， and actively participate in multidisciplinary team collaboration to ensure the safety and efficacy of patient treatment.

Iron is an indispensable trace element for the human body to maintain normal physiological functions， widely participating in key processes such as oxygen transport， energy metabolism， and cell signal transduction. The homeostasis of iron is crucial for maintaining the structural integrity and functional stability of the cardiovascular system. Recent studies have shown that iron homeostasis imbalance， especially iron overload， has become a major risk factor for the occurrence and development of atherosclerosis （AS）. The downstream-induced ferroptosis can form a "iron overload-lipid peroxidation-inflammation" vicious triangle through multiple pathways such as promoting oxidative stress， lipid peroxidation， and inflammatory response， and the three mutually reinforce each other to accelerate plaque formation and progression. Traditional Chinese medicine （TCM） has demonstrated unique advantages in the prevention and treatment of AS， with definite clinical efficacy. Its mechanism of action， in addition to improving lipid metabolism and protecting vascular endothelium， is closely related to the regulation of iron homeostasis in the body. From the new perspectives of systemic iron homeostasis imbalance and the "iron overload-lipid peroxidation-inflammation" vicious triangle， this article reviews the research progress in the association between iron homeostasis imbalance and AS in recent years， and integrate the mechanism of iron homeostasis imbalance in modern medicine with the TCM theory of stasis and toxin interconnection. It focuses on exploring the potential molecular mechanisms of TCM in regulating iron homeostasis through intervention in key pathways of iron overload and inhibition of ferroptosis， summarizes the "iron reduction-antioxidation-anti-inflammation" network constructed by TCM compound prescriptions， and the characteristics of TCM active components in synergistically resisting systemic iron homeostasis imbalance through sharing key targets such as nuclear factor erythroid 2-related factor 2 （Nrf2） and nuclear factor （NF）-κB. This article provides ideas and a theoretical basis that combine the characteristics of TCM theory with modern scientific evidence for the prevention and treatment of AS.