Objective To evaluate the safety of the 13-valent pneumococcal polysaccharide conjugate vaccine (tetanus toxoid/diphtheria toxoid) (PCV13-TT/DT) among age-eligible children in Tianjin through a combination of active and passive surveillance methods. Methods From July 15, 2023, to August 31, 2024, active surveillance for adverse events following immunization (AEFI) was conducted among recipients of PCV13-TT/DT at 18 selected vaccination clinics in Tianjin. Recipients were monitored through on-site observation or telephone follow-up within 30 minutes after vaccination and on days 1, 3, 7, and 28. Passive surveillance for AEFI was conducted among recipients of PCV13-TT/DT at other vaccination clinics across the city. The incidence of AEFI was analyzed using descriptive epidemiological methods. Results A total of 24 916 recipients of PCV13-TT/DT were observed, with 440 AEFI cases reported, resulting in an overall incidence rate of 176.59 per 10 000. The incidence rate of AEFI in active surveillance was 813.79 per 10 000, significantly higher than that in passive surveillance (20.49 per 10 000; P< 0.001). The incidence rates of general reactions, abnormal reactions, and coincidental cases in active surveillance were 744.44 per 10 000, 8.16 per 10 000, and 61.19 per 10 000, respectively, all of which were higher than those in passive surveillance (18.49 per 10 000, 0.50 per 10 000, and 1.50 per 10 000), with P values < 0.05. General reactions were mainly characterized by fever, local redness, and local induration. Abnormal reactions included angioedema and allergic rash. Coincidental cases were mainly infections. No severe adverse reactions occurred. Conclusion The large-scale vaccination of PCV13-TT/DT after its launch has good safety, and continuous strengthening of vaccine safety monitoring is needed.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

As the core hub of energy metabolism in eukaryotes, mitochondria participate in a variety of cellular activities, including metabolic regulation of the cell matrix, apoptosis, and the activation of signal transduction pathways. Their functional status is closely linked to the initiation and progression of various diseases. Neurodegenerative diseases are primarily characterized by the progressive loss and dysfunction of neurons, and mitochondrial dysfunction is considered one of the key triggers in this process. The specific mechanisms by which mitochondrial dysfunction contributes to neurodegenerative diseases have attracted widespread attention. When misfolded or unfolded proteins are detected, a process known as the mitochondrial unfolded protein response (mtUPR) is activated to promote proper protein folding or degradation, thereby restoring mitochondrial function. As a mitochondrial stress defense mechanism, mtUPR primarily regulates the expression of nuclear-encoded genes, such as chaperones and proteases, to alleviate mitochondrial stress. Studies have shown that, in addition to misfolded and unfolded proteins, other mitochondrial stresses—such as mitochondrial DNA abnormalities and reactive oxygen species (ROS)—can also induce mtUPR. The biological functions of mtUPR extend beyond mitochondria and are crucial for the health of the entire cell and even the whole organism. The mtUPR process involves communication between mitochondria and the nucleus, a phenomenon that is highly conserved and has been observed across different species. Abnormal activation or inhibition of mtUPR is closely associated with the development of various neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. An in-depth exploration of the dynamic regulatory role and molecular mechanisms of mtUPR is therefore of great significance for understanding the pathogenesis of these disorders. In addition to neuron loss, neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain, including insoluble fibrils of amyloid beta, phosphorylated tau, or α-synuclein. While the molecular pathways of mtUPR are largely conserved across different diseases, the possibility of differential regulatory factors cannot be excluded. Although mtUPR activation is predominantly recognized for its cytoprotective role, it may exert deleterious effects when overstimulated or sustained. Chronic mtUPR activity has been linked to mitochondrial dysfunction and increased neuronal vulnerability, contributing to the pathogenesis of various neurodegenerative diseases. This review summarizes the fundamental concepts, major inducers, and signaling pathways of the mtUPR. We focus on the intrinsic relationship and regulatory patterns between mtUPR and neurodegenerative diseases, providing insights that may aid the development of targeted therapies. Finally, we discuss the challenges and future directions of mtUPR research in this field, aiming to pave the way for new therapeutic breakthroughs. A major limitation arises from the experimental models currently used; most findings rely on model organisms or cultured cells, which cannot fully replicate the complexity of human neurons. Future research should therefore focus on three main directions: (1) defining the molecular switches that determine whether mtUPR acts in a protective or detrimental manner; (2) elucidating differences in mtUPR molecular pathways across various models of neurodegenerative diseases; and (3) establishing robust biomarkers for mtUPR activity.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

ObjectiveTo investigate the changes in chemical components of Gardeniae Fructus（GF） before and after being charred， providing data support for research on the material basis of GF Carbonisata（GFC）. MethodsUltra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Orbitrap MS/MS） was used to conduct a comprehensive analysis of the chemical components in GF and GFC under positive and negative ion modes with Compound Discoverer 3.3 software and online database. Then， principal component analysis and partial least squares-discriminant analysis in SIMCA14.1 software were used to analyze the MS data of each sample. Based on the principle of variable importance in the projection（VIP） value>1， differential secondary and primary metabolites before and after carbonization were screened. In addition， MetaboAnalyst website was used for pathway enrichment of Kyoto Encyclopedia of Genes and Genomes（KEGG）， so as to provide a reference for clarifying the processing mechanism. ResultsA total of 185 components were identified， including 96 secondary metabolites and 89 primary metabolites. These components were classified into nine categories， primarily including iridoid glycosides， flavonoids， and terpenoids， their fragmentation pathways were also analyzed. Simultaneously， multivariate statistical analysis was performed on the secondary and primary metabolites， identifying 70 and 59 differential metabolites， respectively. The secondary metabolites were enriched in two metabolic pathways， including C5-branched dibasic acid metabolism and flavonoid and flavonol biosynthesis， while the primary differential metabolites were enriched in seven pathways such as linoleic acid metabolism and tyrosine metabolism. ConclusionThe chemical components of GF change significantly after carbonization， with a significant decrease in the contents of iridoid glycosides and terpenoids such as hydroxyisogeniposide， crocin Ⅱ， crocetin， and jasminoside B. while the contents of 4-hydroxycoumarin， geniposidic acid， gentiopicroside， and gardenoside methyl ester increase significantly. This change is presumed to be associated with the enhanced cooling and hemostatic effects of the processed products. The identified key components provide a basis for elucidating the material basis underlying the efficacy changes before and after carbonization.

This article systematically reviews and verifies the name， origin， production area， quality evaluation， harvesting， processing and other aspects of Cynanchi Atrati Radix et Rhizoma（CARR） by consulting relevant ancient and modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research， Baiwei has been the official name for CARR， though it also bears alternative names such as Chuncao， Popo Zhenxianbao， Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong， Anhui， Jiangsu， Shaanxi and Shanxi. Since the late Ming dynasty， varieties from Juxian， Yishui and Rizhao in Shandong have been highly regarded as authentic， commonly known as eastern Baiwei. Since modern times， its quality has been summarized as fine， slender， and straight fibrous roots， pale yellow exterior， whiter interior， and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month， but after the Song dynasty， harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade， removing Lu（the little rhizomes which are on tap of roots）， and removing mustaches， modern methods involve washing and sun-drying. During the Northern and Southern dynasties， processing methods included steaming. In the Song dynasty， drying and light stir-frying were predominant， while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw， stir-frying or honey processing. Regarding the medicinal properties of CARR， both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold， while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty， there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach， liver， and kidney meridians. Throughout history， its main functions have been to clear heat， diuresis， nourish Yin， and replenish essence， primarily treating Yin deficiency and fever syndrome. Based on the research results， it is suggested that when developing famous classical formulas containing CARR， the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements， raw products can be selected as medicine. If the processing requirements are specified， corresponding processed products can be selected as medicine according to the original formula requirements.

The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.