ObjectiveTo investigate how vitamin B₁₂ eye drops regulate MMP-9 and TNF-α expression levels in the corneas of dry eye disease （DED） mouse model induced by a combination of an artificially simulated dry environment （air humidity 30%） and subcutaneous injection of hyoscine hydrobromide. MethodsFifty C57BL/6 female mice were used in the study. 10 mice formed A group （blank control）， while the remaining 40 mice were subjected to dry eye disease induction through subcutaneous injection of scopolamine hydrobromide in a controlled environment with 30% air humidity. All mice underwent schirmer I test （SIT）， tear break-up time （TBUT）， and corneal fluorescence staining score（CFS）evaluations. Mice meeting modeling criteria were randomly assigned to three groups： B group （model group）， C group （PBS control）， and D group （vitamin B₁₂ group）. 0， 7， 14， and 21 days after treatment， each group received TBUT， SIT， CFS， and corneal inflammation assessments. Macroscopic analysis evaluated the efficacy of vitamin B₁₂ eye drops in treating dry eye. After 21 days of treatment， all mice were euthanized via cervical dislocation and their corneas analyzed using HE staining to examine morphological changes. ELISA and immunohistochemical methods were employed to detect MMP-9 and TNF-α expression levels in corneal tissues across groups. ResultsIn dry environments （air humidity 30%）， subcutaneous injection of scopolamine hydrobromide induced changes in dry eye-related indicators in mice： SIT significantly decreased， TBUT significantly shortened， corneal fluorescein staining increased， and CFS all significantly elevated （P 0.05）， indicating successful establishment of the dry eye model. A total of 30 dry eye mice were enrolled. When the dry eye model was successfully established without drug intervention， no statistically significant differences were observed between B group， C group and D group in terms of TBUT， SIT， corneal fluorescein staining， or CFS. Compared with A group， B group， C group and D group showed statistically significant differences in reduced SIT， shortened TBUT， increased corneal fluorescein staining， and elevated CFS （P 0.05）. After drug intervention， D group （vitamin B₁₂ group） exhibited significantly increased SIT， prolonged TBUT， reduced corneal fluorescein staining， clearer corneas， decreased fluorescein staining， and lower CFS compared with B and C groups（P 0.05）. ELISA and immunohistochemical staining results showed that compared with A group， B and C groups exhibited significantly increased expression of MMP-9 and TNF-α in corneal tissues （P 0.05）. D group showed decreased expression of MMP-9 and TNF-α compared with B and C groups but remained higher than A group （P 0.05）. ConclusionThe expression of MMP-9 and TNF-α in the corneal tissues of mice with dry eye is elevated， suggesting that both inflammatory factors， MMP-9 and TNF-α， are involved in the development of dry eye. Vitamin B₁₂ eye drops may improve the symptoms of ocular surface discomfort by promoting the repair of the corneal epithelium. Vitamin B₁₂ eye drops may increase tear secretion， prolong tear film break up time， reduce corneal fluorescein staining， and alleviate the inflammatory reaction of the cornea by decreasing the expression of MMP-9 and TNF-α in the corneal tissues of the mice， thus playing a therapeutic role in the treatment of dry eye disease.

Objective:To assess the viability of reducing radiation dose, contrast media volume, injection flow rate and contrast medium concentration (quadruple low-dose protocol) by utilizing virtual monoenergetic images (VMI) in photon-counting detector CT (PCD-CT) for aortic CT angiography (CTA), while maintaining image quality in comparison to images obtained from energy-integrating detector CT (EID-CT).Methods:From April 2024 to June 2024, a total of 40 participants who underwent aortic CTA on PCD-CT were prospectively enrolled in the experimental group (PCD-CT group), while 40 patients with similar baseline characteristics who had previously undergone aortic CTA using EID-CT were retrospectively selected for the conventional group (EID-CT group). The EID-CT group used a tube voltage of 90 kVp, a contrast media volume of 60 ml of contrast, an injection flow rate of 3 ml/s, and a contrast concentration of 350 mgI/ml; the PCD-CT group used the QuantumPlus mode, with a tube voltage of 140 kVp, a total amount of iodine in the contrast media of 140 mgI/kg, and an injection flow rate=contrast media volume/(delay time+scan time), and a contrast media concentration of 320 mgI/ml. VMIs in PCD-CT group were reconstructed in 5-keV intervals ranging from 45 to 65 keV. The effective radiation dose and contrast injection protocols were recorded and compared between two groups. Objective image quality assessment was performed for each group. CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at five anatomical locations (ascending aorta, aortic arch, descending aorta, abdominal aorta, and right common iliac artery), and image noise was recorded. Subjective image quality was independently evaluated by two readers using a 5-point Likert scale in a blinded manner. Based on data normality, the one-way ANOVA or Kruskal-Wallis test was used for image quality assessment, with Bonferroni-corrected post-hoc analysis for multiple comparisons.Results:There were no significant differences in the baseline characteristics between two groups (all P0.05). The PCD-CT group demonstrated significantly lower effective radiation dose [(3.88±0.65) mSv vs. (5.97±1.15)mSv], contrast media volume [(29.25±4.56) ml vs. 60 ml], and injection rate [(2.65±0.42) ml/s vs. 3 ml/s] than the EID-CT group, with reductions of 35%, 51%, and 12%, respectively (all P0.001). For objective image quality, except for the ascending aortic CT attenuation, the CT attenuation, SNR, and CNR of other vessels in the 55 keV PCD-CT group were comparable to those in the EID-CT group. Additionally, the difference in image noise between these two groups was not statistically significant ( P0.05). Concerning subjective image quality, at 55 keV, the PCD-CT group had similar image noise scores and vessel attenuation scores (both P0.05) and better visualization of renal artery branching ( P=0.001) compared to the EID-CT group. Conclusion:In comparison to EID-CT, the use of a 55 keV image in PCD-CT for aortic CTA has demonstrated reductions in radiation dose, contrast media volume, injection flow rate and contrast medium concentration, while maintaining image quality.

Objective:To evaluate the feasibility of head and neck vascular imaging using photon-counting detector computed tomography (PCD-CT) combined with a “quadruple lows” protocol—characterized by low contrast media volume, low iodine concentration, low injection rate, and low radiation dose—and to compare the image quality with that obtained by energy-integrating detector CT (EID-CT).Methods:A total of 105 patients with suspected cerebrovascular disease were prospectively enrolled at the First Affiliated Hospital of Zhengzhou University between April and June 2024. Patients were randomly assigned to three groups ( n=35). Group A underwent conventional head and neck CTA using EID-CT. Group B underwent PCD-CT with a protocol involving ultra-low contrast media volume, low iodine concentration, and low injection rate. Group C underwent PCD-CT with the full “quadruple low” protocol. Objective image quality parameters—including CT attenuation, image noise (standard deviation, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)—were measured at the ascending aorta, common carotid artery, internal carotid artery, vertebral artery, basilar artery, posterior cerebral artery, and middle cerebral artery. Two radiologists independently rated subjective image quality using a 5-point Likert scale. Differences among groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Results:Compared to Group A [contrast volume: (42.78±6.64)ml], contrast agent volume was significantly reduced in Groups B and C[ (26.26±4.45) ml and (26.54±3.83)ml, respectively], demonstrating reductions of 39% and 38% (both P<0.01). The iodine concentration was 320 mg/ml in Groups B and C, lower than 350 mg/ml in Group A (8.5%). The injection rate was also reduced in Groups B and C [(3.39±0.61) and (3.55±0.51)ml/s, respectively] compared to Group A [(4.28±0.66) ml/s], with reductions of 21% and 17% (both P<0.01). The effective dose (ED) was similar between Groups A and B [(1.40±0.15) vs. (1.40±0.19)mSv, P>0.05], while Group C demonstrated a significantly lower ED [(0.99±0.09) mSv], with a reduction of 30% compared to Group A and 29% compared to Group B (both P<0.01).In terms of objective image quality, significant differences in image noise (SD) were observed among the three groups at the vertebral artery, internal carotid artery, posterior cerebral artery, and middle cerebral artery (all P<0.05). Groups B and C showed significantly lower SD compared to Group A ( P<0.05), with no significant difference between B and C ( P>0.05). SNR was significantly higher in Groups B and C than in Group A at multiple vascular segments (all P<0.05). CNR differed only at the internal carotid artery, where Groups B and C demonstrated superior performance compared to Group A ( P<0.05).Subjective image quality scores showed no significant difference between Groups A and C ( P>0.05), while Group B had significantly higher scores than both A and C ( P<0.05). All images were deemed diagnostically acceptable. Conclusion:Compared with conventional EID-CT, PCD-CT combined with a “quadruple lows” protocol enables substantial reductions in contrast media and radiation dose while further improving image quality in head and neck CTA.

Objective To observe the feasibility of photon-counting detector(PCD)-CT combined with"four-lows"protocol(low contrast agent concentration,low contrast dose,low contrast agent flow rate,low radiation dose)for coronary CT angiography(CCTA).Methods Totally 106 patients with suspected coronary artery disease were prospectively enrolled and randomized into energy-integrating detector(EID)-CCTA(group A,using conventional scanning protocol,n=52)or PCD-CCTA(group B,using"four-lows"scanning protocol,n=54)groups and underwent relative examinations.The radiation dose,subjective and objective evaluation results of imaging quality were compared between groups.Results The contrast agent dose and flow rate,volume CT dose index,dose length product and effective dose in group B were all lower than those in group A(all P＜0.001).The subjective scores in group B were higher than in group A(5[4,5]vs.4[4,5],Z=-2.310,P=0.021).Compared with group A,CT value,signal-to-noise ratio and contrast-to-noise ratio of aortic root and most of the main branches of coronary arteries increased in group B,while standard deviation of CT value decreased(all P＜0.05).Conclusion PCD-CT combined with"four-lows"protocol could be used for CCTA,which could improve imaging quality and reduce contrast agent usage and radiation dose.

Objective:To explore the diagnosis and treatment strategy of emphysematous pyelonephritis (EPN).Methods:The clinical data of 11 cases patients with EPN admitted to 3 hospitals from March 2016 to June 2022 were retrospectively analyzed, among them, 4 cases from Qianhai Shekou Free Trade Zone Hospital, 5 cases from the Second Hospital Affiliated to Kunming Medical University, 2 cases from the Second Affiliated Hospital of Hubei University of Scinece and Technology. Among the 11 patients, 2 were males and 9 were females, aged 50-82 years; the lesions were located on the left side in 6 cases, right side in 4 cases and bilateral in 1 case; all patients had type 2 diabetes and poor glycemic control. The clinical manifestations at admission including back pain in 8 cases, fever in 11 cases, nausea and vomiting in 5 cases, disturbance of consciousness in 3 cases, septic shock in 3 cases, accompanied with ureteral or kidney stones in 5 cases. The pathogenic bacteria were Escherichia coli in 8 cases, Klebsiella pneumoniae in 2 cases and Proteus mirabilis in 1 case. All patients received minimally invasive surgery, anti-infection, subcutaneous injection of insulin, fluid rehydration and nutritional support after admission. 2 cases had a combination of an initial ureteral stenting and second stage percutaneous drainage, 3 patients underwent ureteral stent implantation, 6 patients underwent percutaneous drainage. According to the CT classification of EPN, there were 1 case of type Ⅰ, 3 cases of type Ⅱ, 2 cases of type ⅢA, 4 cases of type ⅢB, and 1 case of type Ⅳ. Results:All 11 cases were cured, 4 cases were admitted to intensive care unit for 2-7 days, 1 case underwent nephrectomy during hospitalization, and 1 case underwent nephrectomy due to renal atrophy during follow-up. After 12 to 18 months of follow-up with urinary CT or B-ultrasound, there were no recurrence cases.Conclusions:EPN is a rare and serious renal parenchymal necrotic infection. Early urinary CT examination is necessary for the diagnosis, and positive minimally invasive surgery combined with comprehensive medical treatment is the preferred treatment strategy. If those above treatment does not work, nephrectomy should be performed.

The inherent complexity of Alzheimer's disease (AD) and failed clinical trials have spiked the interest in multifunctional ligands that target at least two key disease-associated macromolecules in AD pathology. Here we present a focused series of pleiotropic N-carbamoylazole prodrugs with dual mechanism of action. Pseudo-irreversible inhibition of the first therapeutic target, human butyrylcholinesterase (hBChE), enhances cholinergic transmission, and thereby provides symptomatic treatment, same as the standard therapeutics in use for AD. Simultaneously, this step also functions as a metabolic activation that liberates a nanomolar selective α ₂-adrenergic antagonist atipamezole, which blocks pathological amyloid β (Aβ)-induced and noradrenaline-dependent activation of GSK3β that ultimately leads to hyperphosphorylation of tau, thus achieving a disease-modifying effect. Lead compound 8 demonstrated long-term pseudo-irreversible hBChE inhibition, metabolic activation in human plasma, blood-brain barrier permeability, and p.o. bioavailability in mice. Multi-day in vivo treatment with 8 in an Aβ-induced AD murine model revealed a significant alleviation of cognitive deficit that was comparable to rivastigmine, the current drug of choice for AD therapy. Furthermore, decreased GSK3β activation and lowered tau phosphorylation were observed in APP/PS1 mice. This surpasses the symptomatic-only treatment with cholinesterase inhibitors, as it directly blocks an essential pathological cascade in AD. Therefore, these multifunctional α ₂-adrenergic antagonists-butyrylcholinesterase inhibitors, exemplified by lead compound 8, present an innovative, small molecule-based, disease-modifying approach to treatment of AD.

BACKGROUND: Acupuncture is widely used in modulating brain excitability and motor function, as a form of complementary and alternative medicine. However, there is no existing meta-analysis evaluating the effectiveness and safety of acupuncture on corticospinal excitability (CSE), and the credibility of the evidence has yet to be quantified. OBJECTIVE: This study was designed to assess the efficacy and safety of electroacupuncture (EA) and manual acupuncture (MA) in enhancing brain excitability, specifically focusing on CSE as measured by transcranial magnetic stimulation (TMS). SEARCH STRATEGY: This study followed a systematic approach, searching 9 databases up to August 2024 and examining grey literature, in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INCLUSION CRITERIA: Studies were included if they compared the clinical efficacy of EA or MA with sham acupuncture, no treatment or usual training. DATA EXTRACTION AND ANALYSIS: Three investigators independently conducted literature screening, data extraction, and risk of bias assessment. The primary outcome focused on motor-evoked potentials as measured by TMS, with treatment effects quantified using mean differences or standardized mean differences between pre- and post-treatment. Subgroup analyses were conducted using mixed-effects models, while random-effects or fixed-effects models were used to estimate average treatment differences across studies. RESULTS: Based on 34 studies involving 1031 adults, acupuncture techniques significantly enhanced CSE. EA had a greater impact than MA, with effect sizes of 0.53 mV vs 0.43 mV (95% confidence interval [CI]: [0.30, 0.76], P < 0.00001 vs 95% CI: [0.28, 0.59], P < 0.00001). The 5 most frequently used acupoints were LI4 (Hegu, 32 times), ST36 (Zusanli, 10 times), LI11 (Quchi, 7 times), TE5 (Waiguan, 6 times), and GB34 (Yanglingquan, 5 times). CONCLUSION This systematic review indicates that both EA and MA could effectively and safely enhance CSE, bringing the corticospinal pathway closer to the threshold for firing, which may ultimately improve motor function. LI4, ST36, LI11, TE5 and GB34 are the most commonly used acupoints. Please cite this article as: Liu R, Moe AAK, Liu W, Zoghi M, Jaberzadeh S. Does acupuncture at motor-related acupoints affect corticospinal excitability? A systematic review and meta-analysis. J Integr Med. 2025; 23(2): 113-125.
Humans ; Evoked Potentials, Motor/physiology* ; Acupuncture Points ; Acupuncture Therapy/methods* ; Transcranial Magnetic Stimulation ; Electroacupuncture ; Pyramidal Tracts/physiology*

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.

BACKGROUND:Matrigel is the best material for the culture of tumor organoids,but matrigel alone is not enough to simulate the mechanical environment of tumor growth in vitro.Although the introduction of sodium alginate material can improve the stiffness of the hydrogel based on matrigel,its mechanical properties of hydrogel are difficult to maintain stability in long-term culture.OBJECTIVE:To introduce a small amount of calcium ions into the medium of breast cancer organoids and to observe its maintenance effect on the long-term mechanical properties of the matrigel-sodium alginate hydrogel.METHODS:(1)Sodium alginate composite hydrogels with low,medium,and high stiffness were prepared by introducing different mass concentrations(0,2.5,and 5 mg/mL)of sodium alginate into the constant mass concentration(5 mg/mL)of matrigel.The mechanical properties of hydrogels were measured regularly by rheometer.(2)Human triple negative breast cancer cells MDA-MB-231 were resuspended in hydrogel pre-gels with different stiffness.After gelling,breast cancer organoid factor medium containing(or without)calcium ions was added for breast cancer organoid culture.At a set time point,rheometer was used to regularly measure the effect of calcium ion introduction on the mechanical properties of hydrogel.The morphologic changes of breast cancer organoids were observed under optical microscope.Rate of breast cancer organoids forming into pellets was calculated on day 13.After 7 days of breast cancer organoid culture,different concentrations of the chemotherapy drug docetaxel(0.1,1,10,and 100 nmol/L)were added for intervention for 6 days.Cell viability was detected and the semi-inhibitory concentration of docetaxel,IC50,was calculated.RESULTS AND CONCLUSION:(1)The introduction of sodium alginate effectively improved the mechanical strength of the composite hydrogel.(2)With the extension of breast cancer organoid culture time,the mechanical strength of hydrogels decreased.On day 13 of culture,the mechanical properties of medium and high stiffness hydrogels in the culture environment containing calcium ions were significantly higher than those in the culture environment without calcium ions(P<0.05).There was no significant change in the mechanical properties of low stiffness hydrogels in the two cultures(P>0.05).In long-term culture(13 days),breast cancer organoids changed from round to spindle shape with the decrease of hydrogel mechanical properties in the medium and high stiffness hydrogel groups.After the introduction of calcium ions,the morphology of breast cancer organoids did not change with the extension of culture time in the two groups.The introduction of calcium ions in the culture environment had no effect on the pellet formation rate of breast cancer organoids in the low stiffness hydrogel group,but could improve the pellet formation rate of breast cancer organoids in the medium and high stiffness hydrogel groups.(3)In the culture environment without calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration,and there was no significant difference in IC50 among the three hydrogel groups(P>0.05).In the culture environment containing calcium ions,the cell viability of breast cancer organoids decreased with the increase of docetaxel concentration.The cell viability of breast cancer organoids in the medium and high stiffness hydrogel groups was stronger than that in the low stiffness hydrogel group,and the IC50 was higher than that in the low stiffness hydrogel group(P<0.05).(4)The results showed that the mechanical properties of the matrigel-sodium alginate hydrogel could be maintained by introducing calcium ions into the breast cancer organoid culture system.