Background The impact of cold spells on population health can be categorized into an independent main effect of extreme low temperatures and an added effect of prolonged low temperatures. However, studies on the added effects of cold spells on hospitalizations remain limited. Objective To investigate the added effects of cold spells on hospitalizations of residents in Hengyang City, Hunan Province, and to provide a scientific basis for establishing a cold spell early warning system. Methods Daily meteorological data, air pollutant data, and hospitalization data from six tertiary hospitals of four districts in Hengyang City from 2017 to 2023 were collected. A generalized linear model (GLM) combined with a distributed lag nonlinear model (DLNM) was used to assess the added effects of cold spells on non-accidental hospitalizations, as well as hospitalizations for circulatory system diseases and respiratory system diseases, after controlling the main effect of temperature. The modifying effects of cold spell characteristics (intensity and duration) and individual characteristics (gender and age) were also analyzed. Results Compared with non-cold spell periods, the relative risks (RRs) of total non-accidental hospitalizations and hospitalizations across disease categories, genders, and age groups were elevated during cold spells of varying intensities and durations. However, the total effects of cold spells exhibited a "U-shape" nonlinear relationship with intensity and decreased with prolonged duration. During high-intensity cold spells (daily average temperature < P₅ and lasting ≥ 2 d), the RR (95%CI) for non-accidental hospitalizations was 1.71 (1.21, 2.42); the RRs (95%CIs) for males and females were 1.99 (1.38, 2.84) and 1.47 (1.00, 2.16), respectively; for individuals < 65 years and ≥ 65 years, the RRs (95%CIs) were 1.59 (1.12, 2.26) and 1.93 (1.27, 2.92), respectively; and for circulatory and respiratory system diseases, the RRs (95%CIs) were 1.84 (1.22, 2.79) and 1.07 (0.71, 1.60), respectively. No statistically significant differences were observed between the above subgroups. The single-day lagged effects of cold spells displayed a two-peaked pattern. The single-day lag RR for total non-accidental hospitalizations peaked at lag 1 d after cold spell exposure, declined thereafter, and began to rise again after lag 5 d, reaching a second peak at lag 12–13 d before gradually decreasing. The lagged effects remained statistically significant during lag 8–18 d. The lag patterns of cold spell associations across disease categories, genders, and age groups were largely consistent with those of total hospitalizations. Conclusion Cold spells have a significant impact on non-accidental hospitalizations of residents in Hengyang City, with notable lagged effects. The findings provide important theoretical support for establishing a more targeted cold spell early warning system.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To compare the efficacy of gasless robotic surgery via transaxillary approach and combined axillary-retroauricular approach for unilateral N1b PTC, and to explore the safety and effectiveness of gasless robotic surgery via transaxillary approach for unilateral N1b PTC. Methods:Unilateral N1b PTC patients who underwent surgery in the Department of Otolaryngology, Sun Yat Sen Memorial Hospital, Sun Yat sen University between July 2016 and December 2024 were included and analyzed. According to the inclusion and exclusion criteria and the differences of surgical approaches, the patients were divided into the transaxillary approach（TA） group and the combined axillary-retroauricular approach（TARA） group. The demographic data, operation time, intraoperative blood loss, postoperative drainage volume, postoperative complications, shoulder function evaluation, postoperative visual analogue scale（VAS） of neck aesthetics and recurrence of the two groups were statistically analyzed. Results:A total of 88 patients undergoing gasless robotic surgery were included in this study, including 23 cases in the TA group and 65 cases in the TARA group. The proportion of males in the TA group was significantly higher than that in the TARA group（56.5% vs 21.5%, χ²=9.776, P=0.002）. The total operation time in the TA group was significantly lower than that in the TARA Group（180.00[155.00, 220.00]min vs 220.00[177.50, 272.50]min, z=-2.775, P=0.006）, and the postoperative blood loss in the TA group was significantly lower than that in the TARA Group（30.00[20.00, 50.00]ml vs 50.00[30.00, 60.00]ml, Z=-2.127, P=0.033）. The proportion of area Ⅱ-Ⅴ in the TA group and the TARA group was 87.0% and 70.8%, respectively, and there was no significant difference between the two groups（P>0.05）. There was no significant difference in lateral cervical lymph node dissection and central lymph node dissection between the two groups（P>0.05）. During the follow-up period, no recurrence was found in the two groups, and there was no significant difference in the incidence of complications between the two groups（P>0.05）. According to the stratification of dynamic recurrence risk assessment, it can be seen that the proportion of curative effect satisfaction in the TA group was as high as 95.7%, and that in the TARA group was as high as 81.5%, with no significant difference between the two groups. There was no significant difference in VAS score of neck, Constant Shoulder Score and NDⅡ scale between the two groups（P>0.05）. Conclusion:Gasless robotic surgery via transaxillary approach for unilateral N1b PTC is safe and feasible, and the amount postoperative lymph node acquisition is equivalent to that of combined axillary-retroauricular approach, which can provide a new choice for the treatment of unilateral N1b PTC patients.
Humans ; Robotic Surgical Procedures/methods* ; Axilla/surgery* ; Male ; Female ; Operative Time ; Middle Aged ; Adult ; Treatment Outcome ; Postoperative Complications

BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

This study investigates the clinical differentiation and treatment strategies for bipolar disorder （BD） by analyzing the relationship of its core pathomechanisms including qi stagnation， blood stasis， phlegm turbidity， and heat constraint with bile acid metabolism. The imbalance of "yin in form and yang in function" leads to qi stagnation， blood stasis， phlegm turbidity， and heat constraint， which are critical in the pathogenesis and progression of BD. Bile acids regulate neuroinflammation， neural plasticity， and intestinal flora homeostasis through receptor-mediated pathways. It is believed that the physiological functions of bile acids concretely embody the concept of the "liver is yin in form and yang in function" theory. Clinically， prescriptions such as Sini Powder （四逆散） with the function of venting pathogen and resolving constraint， Wendan Decoction （温胆汤） of drying dampness and resolving phlegm， Longdan Xiegan Decoction （龙胆泻肝汤） of clearing liver and draining fire， and Huanglian Ejiao Decoction （黄连阿胶汤） of nourishing yin and blood can be used to nourish liver yin and restore liver yang function. These strategies may improve BD prognosis by modulating bile acid synthesis and metabolism.

Abstract: The differential expression and subcellular localization of single-cell proteins are closely related to the physiological state and pathological mechanisms of the body. The development of single-cell protein in situ imaging methods provides powerful tools for spatial single-cell proteomics research and single-cell protein profiling. This article summarizes the single-cell protein imaging methods developed in recent years, including the circulating immunofluorescence imaging methods based on ordered multi-round antibody incubation, mass spectrometry imaging based on metal element labeled antibodies, fluorescence imaging based on DNA-barcoded antibody, gene encoded fluorescence protein imaging and spectral imaging based on Raman spectroscopy or X-ray spectroscopy, with brief explanation of the imaging principles of these methods. It focuses on the multiple performance, imaging resolution and signal amplification performance of these methods, and analyzes their application characteristics in practical scientific research and clinical work, in the hope of providing some reference for the development of more revolutionary single-cell imaging methods, and promoting the development of biomedical and precision medicine.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective To investigate the effect of curcumin regulating miR-142-5p targeting pleckstrin homology domain containing family A member 3(PLEKHA3)on proliferation,migration and apoptosis of adrenocortical carcinoma cells.Methods Adrenal cortical cancer cells were divided into NC group(normal culture),NC+60 μmol·L-1 curcumin(60 μmol·L-1 curcumin),NC+60 μmol·L-1curcumin+miR-142-5p group(60 μmol·L-1 curcumin and transfected with miR-142-5p mimic),NC+60 μmol·L-1 curcumin+miR-142-5p+PLEKHA3 group(60 μmol·L-1 curcumin and transfected with miR-142-5p mimic+PLEKHA3).Cell proliferation and migration abilities were detected by cell counting kit-8(CCK-8)and Transwell assays.Expression levels of apoptosis-related proteins were detected by Western blotting.At the animal level,a nude mouse model of human adrenal cortical tumor SW-13 cell transplantation was established and divided into control group and 15,30,45,60 μmol·L-1curcumin groups to verify the anti-adrenal cortical carcinoma effect of curcumin in vivo.Results The cell migration numbers in NC group,NC+60 μmol·L-1 curcumin group,NC+60 μmol·L-1+miR-142-5p group and NC+60 μmol·L-1+miR-142-5p+PLEKHA3 group were 135.76±17.42,37.11±10.08,98.31±14.88 and 24.39±5.28;the apoptosis rates were(3.27±0.11)％,(68.80±4.64)％,(25.47±2.39)％and(78.29±5.47)％;the protein expression levels of B-cell lymphoma 2(Bel-2)were 1.00±0.13,0.59±0.11,0.97±0.09 and 0.31±0.06;the protein expression levels of Bel-2 associated X protein were 1.00±0.08,1.38±0.11,0.69±0.05 and 1.93±0.18;there were statistically significant differences between NC group and NC+60 μmol·L-1 group(P＜0.05,P＜0.01).At the animal level,the volumes of the xenograft tumors in control group and 15,30,45 and 60 μmol·L-1 curcumin groups were(1 653.02±435.93),(1 148.77±327.18),(1 054.21±286.06),(996.89±257.62)and(670.64±157.32)mm3;the weights of the xenograft tumors were(1.00±0.17),(0.82±0.09),(0.76±0.12),(0.68±0.13)and(0.44±0.11)g,there were statistically significant differences between 15,30,45 and 60 μmol·L-1curcumin groups and control group(P＜0.05,P＜0.01).Conclusion Curcumin exerts anti-adrenal cortical cancer effects both in vitro and in vivo,may inhibit the proliferation and migration of adrenal cortical cancer cells and promote their apoptosis by regulating the miR-142-5p/PLEKHA3 signaling pathway.This provides a new potential target for the treatment of adrenal cortical cancer.