OBJECTIVE To analyze the chemical constituents of the active parts of Piper wallichii. METHODS The petroleum ether-extract fraction was prepared from the methanol extract of P. wallichii. Separation and purification were performed using semi-preparative high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS Nineteen compounds were isolated from the petroleum ether-extract fraction from the methanol extract of P. wallichii， identified as 3-acetoxybenzyl benzoate （1）， 2-acetoxybenzyl benzoate （2）， 2-methoxybenzyl benzoate （3）， 3-methoxybenzyl benzoate （4）， 4-hydroxy-3-methoxybenzyl benzoate （5）， 3-hydroxybenzyl benzoate（6）， benzyl benzoate （7）， ganschisandrine （8）， lancifolin A （9）， （7R，8R，3′R）-7-acetoxy-3′，4′-dimethoxy-3，4-methylenedioxy-6′-oxo- Δ1′，4′，8′-8.3′-lignan （10）， （7S，8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （11）， （7R， 8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （12）， isodihydrofutoquinol A （13）， licarin A （14）， licarin B （15）， 2-（2′，5′-dimethoxyphenyl）-3，4- dimethyl-5-（3″，4″-dimethoxyphenyl）- tetrahydrofuran （16）， galgravin （17）， velutin （18）， and piyunin A （19）. CONCLUSIONS Compound 1 is a new benzyl benzoate compound. Compounds 3-5， 8 and 9 are isolated from the Piper genus for the first time， while compounds 2， 6， 10-13 and 15-19 are isolated from P. wallichii for the first time.

PURPOSE: Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure. METHODS: A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis. RESULTS: A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850.00, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%. CONCLUSION The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.
Adult ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China ; Logistic Models ; Resuscitation/mortality* ; Retrospective Studies ; Survival Rate ; Thoracotomy/methods* ; Trauma Centers/statistics & numerical data* ; Wounds, Nonpenetrating/surgery*

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

BACKGROUND: Children's respiratory health demonstrates particular sensitivity to air pollution. Existing evidence investigating the association between short-term ozone (O₃) exposure and childhood pneumonia remains insufficient and inconsistent, especially in low- and middle-income countries (LMICs). METHOD: To provide more reliable and persuasive evidence, we implemented a multi-city, time-stratified case-crossover design with a large sample size, using data from seven representative children's hospitals across major geographical regions in China. To avoid the impact of the COVID-19 pandemic, individual-level medical records of inpatient children under 6 years of age diagnosed with pneumonia during 2016-2019 were collected. Conditional logistic regression models were fitted for each city, and city-specific estimates were pooled through a meta-analysis using a random-effects model. RESULTS: In total, the study included 137,470 pediatric pneumonia hospital admissions. The highest pooled estimate for O₃ occurred at lag0-1, with a 10 µg/m³ increase in O₃ associated with a 1.57% (95% CI: 0.67%-2.48%) higher risk of pediatric pneumonia hospital admissions. Stratified analyses indicated that the effects of O₃ were robust across different sexes, age groups, and admission seasons. We also observed a statistically significant increase in risk associated with O₃ concentrations exceeding the World Health Organization Air Quality Guidelines (WHO-AQGs). CONCLUSIONS This study revealed a significant positive association between O₃ and pediatric pneumonia hospital admissions. Our findings substantially strengthen the evidence base for the adverse health impacts of O₃, underscoring the importance of O₃ pollution control and management in reducing the public health burden of pediatric pneumonia.
Humans ; Ozone/analysis* ; China/epidemiology* ; Pneumonia/chemically induced* ; Child, Preschool ; Male ; Female ; Infant ; Cross-Over Studies ; Air Pollutants/analysis* ; Hospitalization/statistics & numerical data* ; Child ; Cities/epidemiology* ; Air Pollution/adverse effects* ; Infant, Newborn ; Environmental Exposure/adverse effects*

OBJECTIVE: To investigate the influence of different scanning conditions on the image quality of medical electron accelerator cone-beam computed tomography (CBCT) and provide a reference for the selection of scanning conditions for different body parts. Methods Set different scanning conditions, the Catphan 503 phantom was scanned using CBCT parameters to analyze the influence of spatial resolution, noise, uniformity, spatial geometric accuracy, and low-contrast resolution on the image quality of CBCT. RESULTS: For the head, chest, and abdomen, with the increase in scanning parameter values, the noise value decreased by 47.4%, 26.1%, and 51.3% respectively, and the uniformity values decreased by 30.2%, 26.6%, and 47.9% respectively. The low-contrast resolution values decreased by 50.6%, 34.2%, and 12.0%. The influence of different scanning conditions on spatial geometric accuracy and spatial resolution is not significant. CONCLUSION Different scanning parameters have a certain influence on the image quality of medical electron accelerator CBCT. Lower scanning parameters can be selected based on individual patients to reduce the additional radiation dose, providing a reference for the safe application of CBCT image guidance in radiotherapy.
Cone-Beam Computed Tomography/instrumentation* ; Phantoms, Imaging ; Particle Accelerators

The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult