ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

Background Air pollution and meteorological factors exert complex nonlinear effects on acute symptoms in the population, with intricate interactions among these factors. Traditional statistical methods struggle to simultaneously address complex nonlinear relationships and multicollinearity issues. Objective To delineate the dynamic effects of air pollutants and meteorological parameters on acute symptoms in three distinct populations with the multicollinearity being addressed and to generate reliable scientific evidence for prevention and control of health risk factors. Methods A time-series study design was employed to collect data on air pollution (daily mean temperature, daily precipitation, daily mean relative humidity, and daily mean wind speed), meteorological factors [Air Quality Index (AQI), fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and 8-hour maximum ozone (O₃)], and acute symptoms such as fever, cough, and sore throat in Jinan from June to December 2023. Key variables were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by generalized additive mixed modeling (GAMM) to analyze the health effects of combined environmental exposures to air pollution and meteorological factors. Linear variables were modeled using linear mixed-effects function, nonlinear variables were smoothed using thin-plate regression splines, and variables with interaction effects were smoothed using low-rank scale-invariant tensor product splines. Fluctuations in independent variables following a normal distribution were treated as sampling errors and incorporated as random effects in the GAMM. Results For fever, the daily mean temperature, daily mean relative humidity, daily mean wind speed, and ambient SO₂ were statistically significant (P<0.05), with daily mean wind speed being a linear influencing factor. When the daily mean temperature was below 3 °C, each 10 °C increase corresponded to a relative risk (RR) of 2.64 (95%CI: 2.50, 2.79). When the daily mean temperature was ≥3 °C, each 10 °C increase corresponded to an RR of 0.86 (95%CI: 0.83, 0.89). Each 10% increase in daily mean relative humidity was associated with an RR of 0.93 (95%CI: 0.89, 0.97). Each 1 m·s⁻¹ increase in daily mean wind speed corresponded to an RR of 1.06 (95%CI: 1.02, 1.10). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.01 (95%CI: 0.98, 1.05), 1.21 (95%CI: 1.17, 1.24), and 0.97 (95%CI: 0.94, 0.99), respectively. For cough, the daily mean temperature, daily mean relative humidity, PM₁₀, and SO₂ were statistically significant (P<0.001), with PM₁₀ being a linear influencing factor. When the daily mean temperature was below 1 °C, each 10 °C increase corresponded to an RR of 1.47 (95%CI: 1.42, 1.52). When the daily mean temperature was ≥1 °C, each 10 °C increase corresponded to an RR of 0.85 (95%CI: 0.82, 0.87). Each 10% increase in daily mean relative humidity was associated with an RR of 0.95 (95%CI: 0.92, 0.98). Each 50 μg·m⁻³ increase in PM₁₀ concentration corresponded to an RR of 1.05 (95%CI: 1.02, 1.08). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥ 12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.00 (95%CI: 0.97, 1.03), 1.12 (95%CI: 1.09, 1.16), and 0.98 (95%CI: 0.95, 1.00), respectively. For sore throat, the daily mean temperature, daily mean relative humidity, daily mean wind speed, PM₁₀, and SO₂ were statistically significant (P<0.05), with daily mean wind speed and PM₁₀ being linear influencing factors. When the daily mean temperature was below 2 °C, each 10 °C increase corresponded to an RR of 1.82 (95%CI: 1.69, 1.96). When the daily mean temperature was ≥2 °C, each 10 °C increase corresponded to an RR of 0.81 (95%CI: 0.77, 0.87). Each 10% increase in daily mean relative humidity was associated with an RR of 0.94 (95%CI: 0.88, 1.00). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.02 (95%CI: 0.97, 1.08), 1.13 (95%CI: 1.08, 1.19), and 0.98 (95%CI: 0.94, 1.02), respectively. Each 1 m·s⁻¹ increase in daily mean wind speed and each 50 μg·m⁻³ increase in PM₁₀ concentration were associated with RR values of 1.06 (95%CI: 1.00, 1.12) and 1.04 (95%CI: 0.98, 1.10), respectively. An interaction effect was observed between daily mean wind speed and PM₁₀: increasing daily mean wind speed non-linearly reduced the impact of PM₁₀, on sore throat whereas PM₁₀ had no significant effect on wind speed. Conclusion This study, by combining LASSO and GAMM, largely eliminates the multicollinearity among selected variables. It reveals complex non-linear effects and interactions between air pollutants, meteorological factors, and acute symptoms in different population groups in Jinan. The symptoms like fever, cough, and sore throat are non-linearly associated with daily mean temperature and SO₂ concentration, while PM₁₀ and wind speed show a linear relationship or interactive effects. These findings provide a new basis for the precise prevention and control of health risk factors.

The paper summarizes the authorized invention patents, device registration and the relevant published articles of acupuncture medical devices of TCM in recent 5 years, and analyzes the current status and challenges in this field. It is discovered that the optimization and substitution in diagnosis and treatment of acupuncture are involved in the development of acupuncture medical devices. The technology application of these devices are composed of traditional and emerging engineering technologies; and the theoretical guidance for their development requires the integration of traditional acupuncture principles with modern medical theories. The development of acupuncture medical devices highlights the characteristics of multidimensional integration, treatment for specific ailments, portability and wearability, painlessness and non-invasion, precision and personalization, as well as intelligent automation. Upon analysis, it is shown that in the development and product transformation of acupuncture medical devices in recent years, the theoretical principles of acupuncture of TCM have not been fully utilized yet, the transformation of patented product is low, the clinical evidence of product is insufficient, and the market competitiveness needs improvement. In the future, The theoretic guidance of acupuncture of TCM should be enhanced in the development of acupuncture medical devices, a production-education- research model with the combination of medicine and engineering be constructed, clinical verification of product be emphasized, and product development paradigms be advanced, so as to meet the demands of the medical market.
Acupuncture Therapy/trends* ; Humans ; Medicine, Chinese Traditional/instrumentation* ; Equipment and Supplies

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.