Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

OBJECTIVE: To observe the clinical efficacy of Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction on acute pharyngitis with lung-stomach heat accumulation. METHODS: A total of 88 patients with acute pharyngitis of lung-stomach heat accumulation were randomly divided into an observation group (44 cases, 4 cases dropped out) and a control group (44 cases, 4 cases dropped out). The control group was treated with oral Qingyan Lige decoction, 150 mL each time, twice a day for 6 continuous days. On the basis of the treatment in the control group, Xujiang Xie's bloodletting therapy was applied at bilateral Shaoshang (LU11), Shangyang (LI1), and Erjian (EX-HN6) in the observation group, 0.1-0.5 mL of bloodletting per site, once every other day for 3 times in total. The TCM symptom and sign score, complete blood count (white blood cell [WBC] count, neutrophilic granulocyte percentage [NE%]), inflammation indexes (serum levels of C-reactive protein[CRP], interleukin[IL]-1β, IL-6, tumor necrosis factor [TNF]-α) and immune indexes (？？, ？？, ？？) of the two groups were observed before treatment and after 6 days of treatment, and the clinical efficacy was evaluated. RESULTS: After 6 days of treatment, the sore throat scores, redness and swelling scores of pharyngeal mucosa and uvula, pharyngeal dry and burning scores, hyperemia scores of posterior pharyngeal lymphoid follicles, chill and fever scores, total scores of TCM symptom and sign, WBC count, NE%, CRP, IL-1β, IL-6, TNF-α and ？？ in both groups were decreased compared with those before treatment (P<0.05), the above indexes in the observation group were lower than those in the control group (P<0.01, P<0.05, P<0.001). After 6 days of treatment, the levels of ？？ and ？？ in both groups were increased compared with those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.001). The total effective rate of the observation group was 95.0% (38/40), which was higher than 90.0% (36/40) in the control group (P<0.001). CONCLUSION Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction could improve the symptoms in patients with acute pharyngitis of lung-stomach heat accumulation, inhibit inflammatory response and improve immune function.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Pharyngitis/drug therapy* ; Adult ; Middle Aged ; Bloodletting ; Young Adult ; Lung/drug effects* ; Combined Modality Therapy ; Interleukin-6 ; Adolescent ; Tumor Necrosis Factor-alpha ; Acute Disease/therapy* ; Treatment Outcome

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

OBJECTIVE To discuss the effect mechanism of atractylodin （ATR） on lung injury and airway inflammation in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. METHODS AECOPD model was established using smoke exposure and intratracheal injection of lipopolysaccharide. Rats were randomly grouped into model group， ATR low-， medium- and high-dose groups （25， 50 and 100 mg/kg）， as well as high-dose ATR+anisomycin [ANS， c-Jun N-terminal kinase （JNK） activator] group （100 mg/kg ATR+5 mg/kg ANS）. Additionally， a non-modeled control group was set up， with 12 rats in each group. Rats in each group were intraperitoneally injected with the corresponding drug solution/normal saline once daily for 14 consecutive days. After the last medication， lung function [peak expiratory flow （PEF）， the ratio of forced expiratory volume （FEV） to forced vital capacity （FVC）， arterial partial pressure of oxygen （PaO2）]， as well as the number of inflammatory cells and the levels of inflammatory cytokines [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β] in bronchoalveolar lavage fluid （BALF）， were measured. The pathological morphology of lung tissue in rats was observed. 163.com The apoptosis of lung epithelial cells was detected， and the expression levels of proteins related to the JNK/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in rat lung tissues were detected. RESULTS Compared with control group， PEF， FEV/FVC and PaO2 of model group were slowed or decreased significantly （P＜0.05）. The number of white blood cells， neutrophils， lymphocytes and macrophages， as well as the levels of IL-1β， TNF-α and IL-6 in BALF， along with the pathological score， the apoptosis rate of lung epithelial cells， and the phosphorylation levels of JNK and p38 MAPK proteins in lung tissues， were all increased or raised significantly （P＜0.05）； lung tissue exhibited severe damage， with disordered cell arrangement and marked infiltration of inflammatory cells. Compared with model group， the levels of above quantitative indicators in rats from all ATR dosage groups showed significant improvement in a dose-dependent manner （P＜0.05）； moreover， the pathological damage in lung tissue was alleviated， with cells arranged in a regular and orderly fashion. Compared with ATR high-dose group， the levels of the above quantitative indicators in rats from the high-dose ATR+ANS group were significantly reversed （P＜0.05）， and the pathological damage in lung tissue was exacerbated. CONCLUSIONS ATR inhibits airway inflammation by suppressing the activity of the JNK/p38 MAPK signaling pathway， thereby improving lung tissue damage in AECOPD rats.

Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

In recent years, research on the quality and safety detection of bear bile powder has mainly involved three aspects. First, the identification of active components and substitutes. Quantitative analysis of bile acids and other components is performed using HPLC, HPLC-tandem mass spectrometry, and other techniques, combined with near-infrared spectroscopy, X-ray diffraction, and polymerase chain reaction to identify adulteration. Isotope fingerprint analysis and glycosylation modification detection are used to distinguish natural products from biosynthetic substitutes, revealing significant differences in δ13C values and the proportion of specific glycosylation modifications between natural bear bile powder and synthetic products. Second, the detection of veterinary drug residues, mainly based on ultra-high performance liquid chromatography-tandem mass spectrometry, which can screen over 100 types of residues, but targeted purification strategies are needed to address interference from the bile acid matrix. Thirdly, heavy metal detection, mainly using inductively coupled plasma mass spectrometry and atomic absorption spectrometry, has revealed that contamination is associated with the breeding environment, with significant regional differences. Related detection technologies are gradually evolving from single-target analysis to multi-modal and intelligent approaches. Existing research faces issues, such as matrix effect interference, lack of international standards, and ethical controversies. It is suggested that future efforts should focus on the interdisciplinary application of detection technologies, develop rapid detection methods such as non-invasive monitoring and microfluidic chips, promote the standardization and equivalence evaluation of synthetic alternatives, and establish a full-chain quality control system integrating spatially resolved mass spectrometry imaging, artificial intelligence, and big data.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

Objective To examine the impact of arid climates on distribution of Oncomelania hupensis snails in the Poyang Lake area, so as to provide insights into precision control of O. hupensis snails in the Poyang Lake area. Methods O. hupensis snails-infested grass islands in Hukou County, Lianxi District and Lushan City in the northern Poyang Lake area, and Jinxian County, Nanchang County and Poyang County in the southern Poyang Lake area were selected as the study areas, and the occurrence of frames with living snails and the mean density of living snails were captured from snail surveys in the study areas in spring and autumn each year from 2006 to 2023. Five years 2007, 2011, 2013, 2019 and 2022 were selected as drought years, and the mean daily water levels were collected at the Xingzi hydrological station in the drought years, normal flow year (2012) and flood year (2020). The numbers of days with water levels ranging from the lower elevation (11 m) to the upper elevation (16 m) for snail survival and the numbers of days with water levels of 11 m and below were collected in the Poyang Lake area, and the changes of snail indicators were compared in different grass islands in the Poyang Lake area before and after drought. Results The numbers of days with water levels ranging from 11 to 16 m were 110, 88, 136 d and 125 d at the Xingzi hydrological station in four drought years 2007, 2011, 2013 and 2019, which were less than in the flow year and flood year, and the days with water levels of 11 m and below were 242, 277, 220 d and 198 d in four drought years 2007, 2011, 2013 and 2019, which were longer than in the flow year and flood year. A total of 416 snails-infested marshlands were surveyed in the Poyang Lake area from 2006 to 2021, and the survey marshlands accounted for 43.12% (307/712) and 46.98% (109/232) of total marshlands in the southern and northern Poyang Lake areas, respectively. The median occurrence of frames with living snails and mean density of living snails were 0.60% (interquartile range, 4.04%) and 0.010 1 snail/0.1 m² (interquartile range, 0.076 1 snail/0.1 m²) in drought years, which were both lower than those [1.33% (5.19%) and 0.022 8 (0.098 9) snail/0.1 m²] in non-drought years (χ²= 42.170 and 44.911, both P values < 0.01). The proportion of grass islands with a continuous decline in snail indicators was higher in the southern Poyang Lake area than in the northern Poyang Lake area after the next year of drought (24.24% vs. 2.33%; χ² = 10.633, P < 0.01), and the proportion of grass islands with rebounding snail indicators was higher in the northern Poyang Lake area than in the southern Poyang Lake area (53.49% vs. 15.76%; χ² = 26.966, P < 0.01). A longitudinal analysis of snail indicators in marshlands with rebounding snail indicators after drought showed 1 to 5 years for return to pre-drought snail status, with a median of 2 (interquartile range, 1) years, and snail status was more likely to rebound if the occurrence of frames with living snails and the mean density of living snails were 2.11% and 0.025 5 snail/0.1 m² and greater in snails-infested grass islands. Conclusions Drought causes a remarkable decline in O. hupensis snail indicators in the Poyang Lake area, with a more remarkable impact in the southern Poyang Lake area, and 1 to 5 years are required for return to pre-drought snail status.

Background Hebei Province is located in the North China Plain. In view of the influence of geological background and the acute and chronic hazards caused by excessive drinking water toxicological indicators, coupled with the large coverage of water supply in urban areas and the existence of self-built water supply facilities, it is necessary to understand the drinking water sanitation status in urban areas and conduct health risk assessment. Objective To investigate main indicators affecting the compliance rate of drinking water quality in urban areas of Hebei and evaluate the chronic non-carcinogenic risks of 11 chemicals. Methods The collection, preservation, and testing of 14299 samples of finished water, tap water, and secondary water supply in urban areas of Hebei Province from 2017 to 2021 were conducted following the Standard examination methods for drinking water (GB/T 5750—2006). A total of 11 chemicals were evaluated according to the Hygienic standards for drinking water (GB 5749—2006). The chronic non-carcinogenic risks of the 11 chemicals in drinking water by oral exposure were assessed using the four-step health risk assessment model developed by the United States Environmental Protection Agency and the Technical guide for environmental health risk assessment of chemical substances (WS/T 777—2021). Results From 2017 to 2021, the compliance rates of arsenic, cadmium, hexavalent chromium, lead, mercury, selenium, cyanide, chloroform, and carbon tetrachloride in drinking water in urban areas of Hebei Province were all 100.00%, and fluoride and nitrate (N) were the main indicators affecting water quality compliance, with compliance rates of 97.68% and 99.53% respectively. The compliance rate of fluoride increased year by year (χ²=178.06, P<0.05), and the concentration showed a downward trend (χ²=563.49, P<0.05). The compliance rate of fluoride in water samples during the wet season was higher than that during the dry season (χ²=5.06, P<0.05). The median concentrations of fluoride and nitrate in drinking water in urban areas of Hebei Province from 2017 to 2021 were 0.36 mg·L⁻¹ and 3.32 mg·L⁻¹, with hazard quotients of 0.15 and 0.05, respectively, both less than 1, suggesting no chronic non-carcinogenic risks, and no significant gender difference was found. The hazard quotient of maximum fluoride concentration was 1.65, which was greater than 1, suggesting chronic non-carcinogenic risks. The chronic non-carcinogenic risks associated with the maximum concentrations of the remaining 10 chemical indicators were all within an acceptable range. Conclusions Nine toxicological indicators in drinking water in urban areas of Hebei Province from 2017 to 2021, except for fluoride and nitrate, are within the national standards. Fluoride and nitrate are the main toxicological indicators that affect the overall compliance rate of water quality, and the chronic non-carcinogenic risks associated with maximum concertration of nitrate and 95% concentration of fluoride are at an acceptable level.