ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

ObjectiveCell adhesion is a critical process that regulates cellular physiological functions. Quantitative characterization of adhesion dynamics is essential for elucidating the intrinsic mechanical mechanisms underlying cellular activities. Although atomic force microscopy-based single-cell force spectroscopy is widely used for single-cell adhesion measurements, it requires complex chemical modifications for preparation of live-cell probes, leading to limitations such as cumbersome operation, low throughput, and potential impacts on cell viability. Fluidic force microscopy, which combines atomic force microscopy with microfluidic probes, is a technique allowing the operation of force-controlled nanopipettes in aqueous environments. By applying negative or positive pressure via a pressure controller, a single living cell can be captured onto or released from the cantilever under physiological conditions. This procedure offers a simple workflow and high assay throughput for single-cell adhesion measurements without the need for chemical functionalization. In this study, fluidic force microscopy-based single-cell force spectroscopy was adopted to achieve long-term quantitative characterization of single-cell adhesion dynamics in a simpler and more efficient manner, comparing the dynamic differences in adhesion establishment between two cell lines with different differentiation levels. MethodsHEK 293T and hTERT RPE-1 cells were non-invasively captured on the cantilever of a fluidic force microscope via its integrated microfluidic system during 40 h of adhesion culture. Cell-substrate detachment assays were performed, and force-distance curves were recorded to extract key mechanical adhesion parameters, including adhesion force, adhesion energy, and maximum detachment distance. These measurements were combined with real-time monitoring of cell spreading area to systematically characterize the dynamic evolution of single-cell adhesion. ResultshTERT RPE-1 cells rapidly entered a stable adhesion phase within 1 h after seeding, with both area-normalized adhesion force and area-normalized adhesion energy reaching peak values. In contrast, HEK 293T cells required 4 h to achieve stable adhesion. Subsequently, the adhesion force, adhesion energy and maximum detachment distance of hTERT RPE-1 and HEK 293T cells stabilized at approximately 240 nN vs. 30 nN, 2.2 pJ vs. 0.12 pJ and 6 μm vs. 4 μm, respectively. hTERT RPE-1 cells reached the peak of area-normalized adhesion parameters earlier than HEK 293T cells, with their peak area-normalized adhesion force and area-normalized adhesion energy being substantially elevated relative to HEK 293T cells. HEK 293T cells presented stronger linear correlations among adhesion energy, maximum detachment distance and adhesion force compared with hTERT RPE-1 cells. For both cell lines, cell spreading area exhibited a weak correlation with adhesion force. Whereas the area-normalized adhesion parameters of HEK 293T cells remained relatively constant throughout the adhesion process, hTERT RPE-1 cells exhibited elevated values in the early phase, followed by a gradual decline. These results indicated distinct dynamic adhesion patterns between the two cell types, with hTERT RPE-1 cells exhibiting stronger adhesion strength and higher adhesion efficiency. ConclusionIn this study, fluidic force microscopy-based single-cell force spectroscopy was successfully applied to perform long-term in situ quantitative measurement of the adhesion dynamics in single adherent cells. The approach revealed divergent adhesion patterns between HEK 293T and hTERT RPE-1 cells, suggesting a close association between cell differentiation and adhesion behaviors. These findings provide quantitative mechanical evidence for further understanding the underlying mechanisms of cell adhesion.

Organophosphorus nerve agents are the most threatening chemical warfare agents and terrorist agents.The number of nerve agents and their related chemicals involved in the verification of Chemical Weapon Convention(CWC)exceeds ten million,with the majority being isomers.Accurate structural identification of these chemicals has always been one of the challenges in CWC related verification analysis.In this work,a total of 17 kinds of alkyl phosphonate isomers and structural analogs from 5 groups were designed and synthesized,and then analyzed by gas chromatography-mass spectrometry(GC-MS)and gas chromatography-infrared spectroscopy(GC-FTIR).The spectra of isomers or structural analogs obtained from two techniques as well as the structural information provided therein were compared and analyzed.The results showed that for isomers or structural analogs with similar MS spectra,FTIR spectra could provided more structural fingerprint information of compounds and had advantages in confirming structures.Combined with the excellent separation ability of GC,GC-FTIR can be used to assist GC-MS in the structural confirmation of alkyl phosphates,achieving rapid and accurate identification of isomers or structural analogues.

In recent years,cancer incidence has been rising.Chemotherapy is a key clinical treatment,yet long-term use of antitumor drugs can lead to multidrug resistance(MDR).This review introduces the causes and mechanisms of MDR,mainly including genomic mutations,cellular autophagy,tumor micro-environment,and apoptosis.Subsequently,the concept and mo-lecular mechanisms of Cuproptosis are introduced,pointing out that the abnormal accumulation of Cu2+in cells and the chain reaction triggered by the binding of excess Cu2+with mitochon-drial enzymes ultimately lead to cell death.Finally,copper ionophores,copper complexes as drugs,and strategies for indu-cing cuproptosis to reverse drug resistance are introduced.The prospects for exploring antitumor drugs that can reverse MDR are briefly discussed,bringing new ideas to overcoming tumor resist-ance.

Objective To investigate the effect of different residence time of povidone iodine on the disinfection effect of conjunctival sac in senile cataract surgery.Methods A total of 396 senile patients who underwent cataract surgery in our hospital were selected and randomly divided into the long-residence group and the short-residence group,with 198 cases in each group.The patients of the long-residence group and the short-residence group were disinfected with a disposable filling 5%povidone iodine on conjunctival sac for 3 minutes and 30 seconds before surgery,respectively.The bacterial detection and bacterial distribution on conjunctival sac,and corneal epithelial cell damage were compared between the two groups.The subjective comfort conditions such as ocular itching,foreign body sensation,erythema,and photophobia after disinfection were recorded.Results There was no significant difference in the bacterial detection rate before and after disinfection between the two groups(P>0.05).The most frequently detected bacteria in the short-residence group was Staphylococcus epidermidis,accounting for 28.79%and 33.33%before and after disinfection,respectively.The incidences of ocular itching,foreign body sensation,erythema,and photophobia after disinfection in the short-residence group were significantly lower than those in the long-residence group(P<0.05),while the rate of corneal epithelial cell damage in the long-residence group was significantly higher than that in the short-residence group(P<0.05).Conclusion The use of disposable filling 5%povidone iodine for disinfection on conjunctival sac for 30 seconds before surgery can achieve a comparable disinfection effect to disinfection for 3 minutes,which has less effect on corneal epithelial cells,and higher ocular comfort.

In recent years,cancer incidence has been rising.Chemotherapy is a key clinical treatment,yet long-term use of antitumor drugs can lead to multidrug resistance(MDR).This review introduces the causes and mechanisms of MDR,mainly including genomic mutations,cellular autophagy,tumor micro-environment,and apoptosis.Subsequently,the concept and mo-lecular mechanisms of Cuproptosis are introduced,pointing out that the abnormal accumulation of Cu2+in cells and the chain reaction triggered by the binding of excess Cu2+with mitochon-drial enzymes ultimately lead to cell death.Finally,copper ionophores,copper complexes as drugs,and strategies for indu-cing cuproptosis to reverse drug resistance are introduced.The prospects for exploring antitumor drugs that can reverse MDR are briefly discussed,bringing new ideas to overcoming tumor resist-ance.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Objective:To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.Methods:Relevant studies were retrieved from PubMed,EMBASE,Cochrane,Web of Science,Sinomed,CNKI and Wanfang data-bases.The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies,and relevant data were extracted.meta-analysis was performed using RevMan 5.4 and RStudio software,and forest plots were generated.Results:Six randomized con-trolled trials(RCTs)were included.Compared with the control group,denosumab significantly reduced the risk of skeletal-related e-vents(HR=0.78,95％CI:0.62-0.93).In terms of safety,denosumab did not increase the risk of total adverse events,severe adverse events and the adverse events higher than CTC grade 3.Conclusion:Denosumab can delay the time to first skeletal-related event with good safety.However,due to the limitations of this study,further high-quality,large-sample,multicenter RCTs are needed to confirm these findings.

Objective:To investigate the surgical efficacy of the modified areolar triangular dermal-glandular composite flap in correcting moderate to severe congenital nipple inversion.Methods:A retrospective analysis was performed on clinical data collected from patients with moderate to severe congenital nipple inversion treated at the Department of Plastic and Aesthetic Surgery, the First Affiliated Hospital of Hainan Medical University, between August 2018 and January 2023. Patients were divided into two groups based on the month of admission: the control group, treated with conventional areolar triangular flap, and the observation group, treated with the modified areolar triangular dermal-glandular composite flap. Postoperatively, nipple appearance, maintenance of nipple height, and incidence of complications were assessed in both groups. At six months after surgery, surgeons evaluated the therapeutic efficacy as good, fair, or poor; the total effective rate was calculated as (number of good + fair cases) / total number of cases ×100%. Patient satisfaction was rated as very satisfied, satisfied, fair, or dissatisfied; the satisfaction rate was calculated as (number of very satisfied + satisfied cases) / total number of cases ×100%. Nipple height (measured as the distance from the areolar plane to the apex of the nipple) was recorded before and after surgery. Measurement data were analyzed using the t-test, and categorical data were analyzed using the χ2 test. A P-value < 0.05 was considered statistically significant. Results:A total of 60 female patients (94 sides) were included in the study. In the control group (28 patients), the mean age was 28.5±5.2 years; 11 cases were unilateral, and 17 cases were bilateral; 22 sides were classified as moderate, and 23 sides as severe. In the observation group (32 patients), the mean age was 29.1±4.8 years; 15 cases were unilateral, and 17 cases were bilateral; 23 sides were moderate, and 26 sides were severe. There were no statistically significant differences between the two groups regarding age, severity of nipple inversion, or the ratio of unilateral to bilateral nipple inversion (all P>0.05). Postoperative follow-up lasted 6 to 15 months, with 28 patients (43 sides) in the observation group and 24 patients (39 sides) in the control group completing follow-up. No severe complications, such as nipple necrosis, occurred in either group, and nipple morphology and appearance were generally normal. The total effective rates based on surgeons' efficacy evaluations were 94.87% (37/39) in the control group and 100.00% (43/43) in the observation group, with no statistically significant difference ( P>0.05). Patient satisfaction rates were 76.92% (30/39) in the control group and 93.02% (40/43) in the observation group, showing a statistically significant difference ( P<0.05). There was no significant difference in preoperative nipple height between the two groups [-3.2±1.1 mm vs. -3.5±0.9 mm, P>0.05]. At 6 months post-surgery, nipple height in the observation group was significantly greater than in the control group [10.9±2.0 mm vs. 9.5±1.9 mm, P < 0.05]. Conclusion:The modified triangular dermal-glandular composite flap technique for correcting nipple inversion is relatively simple, demonstrates low long-term recurrence rates, and provides stable maintenance of nipple height. It is one of the preferred methods for treating moderate to severe congenital nipple inversion.