In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

In this paper， by referring to ancient and modern literature， the textual research of Inulae Flos has been conducted to clarify the name， origin， production area， quality evaluation， harvesting， processing and others， so as to provide reference and basis for the development and utilization of famous classical formulas containing this herb. After textual research， it could be verified that the medicinal use of Inulae Flos was first recorded in Shennong Bencaojing of the Han dynasty. In successive dynasties， Xuanfuhua has been taken as the official name， and it also has other alternative names such as Jinfeicao， Daogeng and Jinqianhua. The period before the Song and Yuan dynasties， the main origin of Inulae Flos was the Asteraceae plant Inula japonica， and from the Ming and Qing dynasties to the present， I. japonica and I. britannica are the primary source. In addition to the dominant basal species， there are also regional species such as I. linariifolia， I. helianthus-aquatili， and I. hupehensis. The earliest recorded production areas in ancient times were Henan， Hubei and other places， and the literature records that it has been distributed throughout the country since modern times. The medicinal part is its flower， the harvesting and processing method recorded in the past dynasties is mainly harvested in the fifth and ninth lunar months， and dried in the sun， and the modern harvesting is mostly harvested in summer and autumn when the flowers bloom， in order to remove impurities， dry in the shade or dry in the sun. In addition， the roots， whole herbs and aerial parts are used as medicinal materials. In ancient times， there were no records about the quality of Inulae Flos， and in modern times， it is generally believed that the quality of complete flower structure， small receptacles， large blooms， yellow petals， long filaments， many fluffs， no fragments， and no branches is better. Ancient processing methods primarily involved cleaning， steaming， and sun-drying， supplemented by techniques such as boiling， roasting， burning， simmering， stir-frying， and honey-processing. Modern processing focuses mainly on cleaning the stems and leaves before use. Regarding the medicinal properties， ancient texts describe it as salty and sweet in taste， slightly warm in nature， and mildly toxic. Modern studies characterize it as bitter， pungent， and salty in taste， with a slightly warm nature. Its therapeutic effects remain consistent across eras， including descending Qi， resolving phlegm， promoting diuresis， and stopping vomiting. Based on the research results， it is recommended that when developing famous classical formulas containing Inulae Flos， either I. japonica or I. britannica should be used as the medicinal source. Processing methods should follow formula requirements， where no processing instructions are specified， the raw products may be used after cleaning.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To analyze the characteristics of viral hepatitis mortality and life loss among residents in Pudong New Area from 2003 to 2023, and to provide a basis for related prevention and control work. Methods Viral hepatitis mortality data were obtained from the Pudong New Area mortality monitoring system. The crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), and standardized potential years of life lost (SPYLL) were calculated to analyze viral hepatitis deaths. The average annual change (AAPC) and annual percentage change (APC) of the mortality rate were calculated by Joinpoint regression analysis to analyze the trend of mortality. Results The CMR and SMR of viral hepatitis among residents in Pudong New Area from 2003 to 2023 were 3.89/100000 and 1.98/100000, respectively. Both CMR and SMR of viral hepatitis showed a decreasing trend over time (CMR:APC=-5.476, t=-13.581, P<0.001; SMR:APC=- 7.624, t= -21.253, P<0.001). The CMR for males was 4.75/100000 and the SMR for males was 2.65/100000; the CMR for females was 3.04/100000 and the SMR for females was 1.32/100000, with a higher mortality rate for males than for females（Z_CME=12.094，P<0.001; Z_SMR=-14.718，P<0.001). Deaths were concentrated in the age groups of 45-64 years old and 65 years old and above, accounting for 91.62% of the total deaths. The PYLL of deaths due to viral hepatitis among residents in Pudong New Area from 2003 to 2023 was 26912 person-years, with a PYLLR of 0.45% and an AYLL of 8.88 years per person. Conclusion The mortality rate of viral hepatitis among the residents of Pudong New Area in 2003-2023 shows a decreasing trend over time. The mortality rate of males is higher than that of females, and the deaths of middle-aged and elderly people account for a large proportion of the total deaths. Chronic hepatitis B is the main cause of death.

Background The crude mortality rate of sudden death has shown a steady upward trend. Pudong New Area, Shanghai, is a highly urbanized and densely populated district that is substantially affected by the urban heat island effect and has experienced frequent extreme temperature events in recent years. However, evidence on the association between ambient temperatures and sudden death among local residents remains limited. Objective To examine the association between daily mean temperature and sudden death in Pudong New Area, and to provide evidence for reducing temperature-related risks of sudden death. Methods Data on sudden death, meteorological factors (daily average temperature, daily average relative humidity, and daily average air pressure), and air pollutants [inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), and nitrogen dioxide (NO₂)] in Pudong New Area from 2016 to 2021 were collected. A distributed lag non-linear model was used to examine the associations of daily mean temperature with total sudden death and sudden death due to cardiovascular and cerebrovascular diseases, including lagged and cumulative effects (lag0, 0-3, 0-7, 0-14, and 0-21 d). Stratified analyses were performed by sex, age, and education level to identify vulnerable populations. The temperature attributable burden of sudden death was assessed by calculating attributable number (AN) and attribute fraction (AF). Results A total of 19458 sudden deaths were reported in Pudong New Area from 2016 to 2021, of which 11082 (56.95%) were due to cardiovascular and cerebrovascular diseases. Both low (P₅, 4.6 ℃) and high (P₉₅, 30.2 ℃) temperatures were associated with increased risks of sudden death. The cumulative risks associated with low temperature peaked at lag 0-21 d for both total sudden death and sudden death due to cardiovascular and cerebrovascular diseases. In contrast, the cumulative risks associated with high temperature peaked at lag 0-7 d for total sudden death and at lag 0-3 d for sudden death due to cardiovascular and cerebrovascular diseases. Stratified analyses showed that females, individuals aged ≥65 years, and those with primary school education or below were more sensitive to low temperature; whereas females, individuals aged <65 years, and those with secondary school education or above were more sensitive to high temperature. Using 21.5 ℃ as the minimum mortality temperature, the AN of total sudden deaths attributable to non-optimal temperature was 3791 (95%CI: 1853, 5587), with an AF of 20.41% (95%CI: 9.47%, 28.94%); the AN attributable to low temperature was 3358 (95%CI: 1087, 5062), with an AF of 17.26% (95%CI: 5.89%, 26.01%), whereas the AN attributable to high temperature was 225 (95%CI: −274, 655), with an AF of 2.03% (95%CI: −2.53%, 5.78%). For sudden deaths due to cardiovascular and cerebrovascular diseases, the AN attributable to non-optimal temperature was 2721 (95%CI: 1747, 5575), with an AF of 24.55% (95%CI: 9.59%, 28.65%); the AN attributable to low temperature was 2496 (95%CI: 988, 3562), with an AF of 22.53% (95%CI: 8.97%, 32.41%), whereas the AN attributable to high temperature was 614 (95%CI: −15, 1176), with an AF of 3.15% (95%CI: −0.08%, 6.02%). Conclusions Both low (P₅, 4.6 ℃) and high (P₉₅, 30.2 ℃) temperatures are associated with increased risks of sudden death in Pudong New Area, Shanghai. High temperature shows a relative short-term effect, whereas low temperature shows a stronger cumulative effect. Females, people ≥65 years, and individuals with primary school educational attainment or below are more vulnerable to low temperature, while females, people <65 years, and those with secondary school educational attainment or above are more vulnerable to high temperature. The attributable burden of low temperature is greater than that of high temperature. Targeted health protection measures should be strengthened for vulnerable populations during extreme temperature events.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry