ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Objective: To analyze the effects of 12week highintensity fitness exercise on body composition,lipid metabolism and gut microbiota in obese adolescents, so as to provide references for improving the health levels of obese adolescents. Methods: From January to June 2023, 20 obese adolescents from Huaifeng Vocational and Technical School in Huaian City were recruited for the study. Participants were assigned to an exercise group (n=10) and a control group (n=10) for a 12week exercise intervention by random number table method, and both groups had the same diet during the intervention period. The exercise group engaged in three exercises every week, mainly consisting of moderate to highintensity aerobic exercise combined with highintensity intervals. In the first week, there was a 30 minutes of aerobic exercise, followed by 10 minutes of highintensity interval training in the total intervention time each week, and the rest of the time was aerobic exercise with a total intervention time of 60 minutes to maintain; the control group did not receive specific interventions. Body composition was measured using bioelectrical impedance analysis, and lipid levels were determined using an automatic biochemical analyzer. The expression levels of serum inflammatory factors were measured at baseline and after 12 weeks of intervention, and gut microbiota was analyzed using 16S rRNA gene sequencing. Statistical analysis was performed using t test and Chisquare test. Results: After 12 weeks of intervention, the levels of triglycerides (TG), and lowdensity lipoprotein cholesterol (LDL-C) in obese adolescents in the exercise group decreased from (1.7±0.6, 3.5±0.8) mmol/L to (0.9±0.3, 2.6±0.4) mmol/L, while highdensity lipoprotein cholesterol (HDL-C) increased from (1.1±0.2) mmol/L to (1.4±0.2) mmol/L; and serum interleukin-1 receptor antagonist(IL-1Rn) decreased from (8.4±1.6) to (4.5±0.4) ng/mL in the exercise group (t=7.34,2.49,-3.05,2.56, P<0.05). The α-diversity results showed that the Chao index (268.00±22.67) and Ace index (243.98±38.64) in the exercise group were higher than those in the control group (184.52±19.28, 171.43±23.33), and the differences were statistically significant (t=2.48, 2.53, P<0.05). The Shannon index (5.36±1.41) in the exercise group was higher than that in the control group (4.73±1.12), and the Simpson index (0.78±0.10) was lower than that in the control group (0.89±0.10), but the differences were not statistically significant (t=1.83, -2.10, P>0.05). The β-diversity results showed that the intergroup differences in gut microbiota structure between the exercise group and the control group were greater than the intragroup differences, and the differences in gut microbiota structure between the exercise group and the control group were statistically significant (R2=0.083，P<0.05). After intervention, there were significant differences in the relative abundances at the levels of phylum, class, genus, and species in gut microbiota among obese adolescents between the exercise group and the control group (P<0.05). Conclusion The 12week highintensity fitness exercise can alleviate obesity symptoms in obese adolescents through the gut microbiota-lipid metabolism pathway and improve mild chronic inflammatory status.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

Objective:To investigate the clinical and imaging characteristics of patients with cryptogenic stroke with different right-to-left shunt (RLS) and possible mechanisms.Methods:Acute ischemic stroke patients aged 18-65 years, who admitted to the Department of Neurology, the First Affiliated Hospital of Fujian Medical University from April 2012 to July 2022, were etiologically classified according to the TOAST criteria. Cryptogenic stroke patients further underwent contrast-enhanced transcranial Doppler (cTCD) examination. Patients with RLS (RLS grade Ⅰ-Ⅳ) were divided into large shunt group (RLS grade Ⅲ-Ⅳ, under normal breathing or after Valsalva manoeuvre) and small shunt group (RLS grade Ⅰ-Ⅱ, under normal breathing or after Valsalva manoeuvre). The chi-square test,Fisher's exact probability method and one-way analysis of variance were used to compare clinical and neuroimaging data between the 2 groups. And the RLS related factors as well as mechanisms of RLS-related stroke were further discussed through Spearman correlation and multiple Logistic regression analysis.Results:A total of 167 cryptogenic stroke patients with RLS were included in this study. The male to female ratio was 88∶79. The onest age was (45.27±9.02) years. In the large shunt group, there were 92 patients (55.1%) with onset age of (45.61±9.32) years. In this group, 35 patients (38.0%) were males, 9 (9.8%) had hypertension, and 18 (19.6%) had smoking history; the Risk of Paradoxical Embolism (RoPE) score was 7.08±0.12. In the small shunt group, there were 75 patients (44.9%) with onest age of (44.85±8.68) years. In this group, 53 patients (70.7%) were males, 29 (38.7%) had hypertension, and 31 (41.3%) had smoking history; the RoPE score was 6.20±0.14. Males (χ 2=17.640, P<0.001) as well as hypertension (χ 2=19.611, P<0.001) and smoking history (χ 2=9.443, P<0.01) were significantly less common in the large shunt group than in the small shunt group, while the RoPE score in the large shunt group was higher than that in the small shunt group ( F=21.580, P<0.001). All 6 pulmonary arteriovenous fistula cases (6.5%, 6/92) belonged to the large shunt group. There was no pulmonary arteriovenous fistula patient in the small shunt group ( P<0.05). There were no statistically significant differences in age of onset, hyperlipidemia, diabetes, previous stroke/transient ischemic attack, or family history of stroke between the 2 groups (all P>0.05). Multiple Logistic regression analysis showed that female ( OR=2.848, 95 %CI 1.223-6.632, P<0.05) and no history of hypertension ( OR=3.937, 95 %CI 1.593-9.727, P<0.01) were significantly associated with large shunt. The neuroimaging features were analyzed through comparing offending vessels as well as spatial distribution of lesions between the 2 groups. Results:showed that infarct location of 54 cases (58.7%) was in the unilateral anterior circulation area, 34 cases (37.0%) in the posterior circulation area, no case in the bilateral anterior circulation area, and both of anterior and posterior circulation areas were involved in 4 cases (4.3%) in the large shunt group. Of all the large shunt group patients, 31 (33.7%) had cortical infarcts, 9 (9.8%) had subcortical infarcts, 36 (39.1%) had deep infarcts, and 16 (17.4%) had mixed multiple infarcts. In the small shunt group, infarct location of 36 cases (48.0%) was in the unilateral anterior circulation area, 29 cases (38.7%) in the posterior circulation area, 4 cases (5.3%) in the bilateral anterior circulation area, and both of anterior and posterior circulation areas were involved in 7 cases (9.3%). Of all the small shunt group patients, 7 (9.3%) had cortical infarcts, 8 (10.7%) had subcortical infarcts, 39 (52.0%) had deep infarcts, and 21 (28.0%) had mixed multiple infarcts. Logistic regression analysis showed that cortical infarction was associated with large shunt ( OR=5.981,95 %CI 1.882-19.007, P<0.01), and there was no statistically significant difference in other types of infarction distribution between the 2 groups (all P>0.05). Conclusions:Among cryptogenic stroke patients with RLS, large shunt was more common in females, patients with no history of hypertension, and those with higher RoPE score as well as more cortical infarction, suggesting that there was a strong link between stroke and large RLS, which revealed the underlying mechanism of embolism in patients with stroke and large RLS. In the small shunt group, there were more males and hypertensive patients, suggesting atherosclerosis was more likely involved in pathogenic mechanism of stroke patients with small RLS.

Objective: To discuss the clinical value of neck circumference in screening for overweight and obesity in children and adolescents, so as to provide a theoretical basis and new ideas for overweight and obesity screening. Methods: From May to July 2023, a total of 2 493 children and adolescents aged 3 to 16 were sampled from three schools by the cluster random sampling method. General data, neck circumference, body mass index (BMI), waisttoheight ratio, and other information were collected. Mann-Whitney ranksum test, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to statistically analyze the data. Results: The prevalence of overweight and obesity in children and adolescents aged 3 to 16 was 33.05%, and the prevalence of abdominal obesity was 28.33%.The neck circumferences of boys and girls in the overweight and obese group showed statistically significant differences from the normal weight group during the preschool, schoolage, and adolescence periods (Z=-16.69--4.54, P<0.05). The neck circumferences of children of different genders were moderately positively correlated with BMI (r=0.50-0.79, P<0.01). ROC curve analysis showed that neck circumference had good accuracy in assisting the screening for the occurrence of overweight and obesity in boys and girls during the preschool, schoolage, and adolescence periods [the AUC for boys:0.80(0.71-0.89), 0.89(0.86-0.91), 0.84(0.81-0.87); the AUC for girls:0.76(0.67-0.86), 0.81(0.74-0.88), 0.73(0.68-0.77), P<0.01], the optimal neck circumference cutoff values for boys were 26.95, 28.95, 33.55 cm, and for girls were 25.05, 26.55, 28.35 cm respectively. The neck circumferences of boys and girls were moderately positively correlated with the waisttoheight ratio during the schoolage and adolescence periods (r=0.41-0.70, P<0.01). ROC curves showed that neck circumferences had good accuracy in assisting the screening for the occurrence of abdominal obesity in boys and girls during the schoolage and adolescence periods [the AUC for boys:0.89(0.86-0.92), 0.82(0.78-0.85); the AUC for girls:0.84(0.75-0.93), 0.87(0.75-0.93)], the optimal cutoff values for boys were 28.95, 32.75 cm; for girls were 26.45, 31.85 cm respectively. Conclusion The neck circumference can be applied to screen for overweight and abdominal obesity in children and adolescents, and can provide new ideas for the prevention and control of overweight and obesity in children and adolescents.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.