ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

ObjectiveTo evaluate and analyze the syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis in a rhein-induced cathartic colon （CC） rat model. MethodsTwenty-four rats were divided into a normal group and a model group （CC group）. The rats were administered equal volumes of physiological saline or 2% rhein suspension by gavage to establish the model over three cycles （approximately 118 days）. The first cycle lasted 46 days， with a dosage of 12 mL·kg^-1·d^-1， administered every other day. The second cycle lasted 37 days， with a dosage of 12 mL·kg^-1·d^-1， administered for 5 consecutive days followed by 2 days of cessation. The third cycle lasted 35 days， with a dosage of 16 mL·kg^-1·d^-1， also administered for 5 consecutive days followed by 2 days of cessation. Each cycle ended when 80% of the rats no longer exhibited loose stools. Body mass， 24 h food intake， coat condition， and coat red （R）， green （G）， and blue （B） values were recorded. The open field test （OFT） was used to measure the total distance traveled to evaluate Qi deficiency. The body mass coefficient and 24 h water intake were recorded to assess Yin deficiency. The sucrose preference test （SPT） was used to determine the sucrose preference rate （SPR）， and the average speed in OFT was measured to evaluate depressive status （liver depression and Qi stagnation）. Tongue images and their R， G， and B values were recorded. Whole blood viscosity （WBV） and plasma viscosity （PV） were measured using an automatic hemorheological analyzer to evaluate blood stasis. A carbon ink propulsion test was performed to determine the intestinal transit rate （ITR） for disease model evaluation. Hematoxylin-eosin （HE） staining was used to observe histopathological changes in the colon. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of transient receptor potential ankyrin 1 （TRPA1） and tryptophan hydroxylase 1 （TPH1） in colon tissue. Western blot was used to detect the protein expression of TRPA1 and TPH1. ResultsIn terms of syndrome indicators， compared with the normal group， the body mass of the CC group decreased （P<0.05）， while 24 h food intake increased （P<0.01）. The coats of the CC group appeared withered， disheveled， and dull， and the R， G， and B values of the coat decreased （P<0.01）. The total distance traveled in OFT decreased （P<0.01）. The body mass coefficient decreased （P<0.01）， while 24 h water intake increased （P<0.05， P<0.01）. The SPR decreased （P<0.01）， and the average speed in OFT slowed （P<0.01）. The tongue appeared dark red， and the R， G， and B values of tongue images decreased （P<0.01）. WBV and PV increased （P<0.01）. Regarding disease indicators， compared with the normal group， the ITR decreased in the CC group （P<0.01）. Pathologically， HE staining showed necrosis and shedding of colonic mucosal epithelial cells， disruption of mucosal continuity， and infiltration of inflammatory cells in the lamina propria in the CC group. Semi-quantitative analysis showed increased HAI scores （P<0.05） and increased inflammatory cell counts and area proportion （P<0.05）. In terms of molecular biological indicators， compared with the normal group， the mRNA and protein expression levels of TRPA1 and TPH1 in colon tissue decreased in the CC group （P<0.05， P<0.01）. ConclusionThe rhein-induced CC rat model conforms to the traditional Chinese medicine syndrome characteristics of Qi and Yin deficiency accompanied by Qi stagnation and blood stasis.

Recent years have witnessed significant advancements in myopia control research through the application of diffuse optical technology(DOT)spectacle lenses. Myopia has emerged as a global public health challenge, affecting nearly half of the world's population, with childhood and adolescent myopia rates continuing to rise. DOT lenses represent an innovative myopia control intervention based on retinal contrast signal theory. These lenses incorporate micro-light scattering dots distributed across the lens surface to reduce retinal imaging contrast and modulate the influence of visual input on axial elongation, thereby slowing myopia progression. The core mechanism operates through refractive index differences between the lens substrate(1.53)and scattering dots(1.50), which generate optical scattering effects. This design maintains clear vision through a central 5 mm optical zone while effectively reducing contrast signal intensity in the peripheral retina. Large-scale randomized controlled trials, including the CYPRESS study, have demonstrated significant myopia control efficacy in children aged 6-10 years: 12-month follow-up data revealed a 74% reduction in myopia progression and a 50% reduction in axial elongation, with sustained safety and visual quality maintained over 4-year long-term follow-up. However, several aspects of DOT technology remain contentious and require further clinical validation, including its applicability across different age groups, optimal scattering dot density configurations, combined application effects with other myopia control methods, and long-term visual adaptation during extended use. This review systematically examines the theoretical foundations, design characteristics, clinical application progress, and future development directions of DOT technology, providing scientific evidence for clinical myopia prevention and control strategy formulation.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P<0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P<0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P<0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P>0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

ObjectiveTo explore the possible mechanism of the treatment of dry eye with liver-meridian constraint-heat syndrome by Runmu Xiaoyao Powder （润目逍遥散） by miR-146a-5p and interleukin-1 receptor-associated kinase 1/tumour necrosis factor receptor associated factor 6/nuclear factor-κB （IRAK1/TRAF6/NF-κB） signalling pathway. MethodsEighty C57BL/6J mice were randomly divided into normal group， model group， agonist group， inhibitor group， sodium hyaluronate group， and Runmu Xiaoyao Powder high-， medium-， and low-dose groups， with 10 mice in each group. Except for the normal group， the mice of dry eye with liver-meridian constraint-heat syndrome were modeled by using benzalkonium chloride solution eye drops combined with chronic pain stimulation. Beginning on the 30th day of modelling， mice in Runmu Xiaoyao Powder high-， medium-， and low-dose groups were given 29， 14.5， and 7.25 g/kg of Runmu Xiaoyao Powder respectively twice daily by gavage； mice in sodium hyaluronate group were given 5 μl of sodium hyaluronate drops twice daily； mice in the agonist group were given 2 nmol of agomir-146a-5p drops in each eye at a time， and those in the inhibitor group were given 5 nmol of antagomir-146a-5p drops in each eye， with every other day， 3 times per week； mice in the normal and model groups were gavaged with deionised water at 1 ml/（100 g·d）. The intervention was continued for 14 days in each group， and mice in each group were examined for tear secretion， tear film rupture time， corneal fluorescein staining， and irritability scores on the day following the last intervention； HE staining was used to observe the pathological conditions of the cornea and lacrimal glands in each group； corneal and lacrimal gland inflammatory factors， such as interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， miR-146a-5p expression， were examined； matrix metalloproteinase 3 （MMP-3） and matrix metalloproteinase 9 （MMP-9） expression in cornea， IRAK1， TRAF6， nuclear factor κB p65 （NF-κB p65） protein and mRNA expression in cornea and lacrimal gland， and phosphorylated nuclear factor κB p65 （p-NF-κB p65） protein expression were detected. ResultsCompared with the normal group， mice in the model group showed reduced tear secretion， shorter tear film rupture time， higher irritability score （P＜0.05）， and pathological examination showed staining in the centre of the cornea， obvious corneal damage， increased volume of lacrimal gland follicular cells， disordered arrangement， a large number of inflammatory cell infiltration， and increased neovascularisation； corneal and lacrimal gland tissues showed elevated expression of IL-1β and TNF-α， decreased expression of miR -146a-5p， elevated expression of IRAK1， TRAF6， NF-κB p65， p-NF-κB p65 protein and IRAK1， TRAF6， NF-κB p65 mRNA， and elevated expression of MMP-3， MMP-9 protein in the cornea （P＜0.05）. Compared with the model group， all of the above indexes were significantly improved in high-dose group of Runmu Xiaoyao Powder， while some indexes were improved in the sodium hyaluronate group and the middle- and low-dose Runmu Xiaoyao Powder groups （P＜0.05）. Compared with the model group， corneal and lacrimal IRAK1 and TRAF6 mRNA and IRAK1， TRAF6 and p-NF-κB p65 protein expression decreased in the agonist group； compared with the inhibitor group， IRAK1， TRAF6， NF-κB p65 mRNA and protein expression in the cornea and lacrimal gland in the Runmu Xiaoyao Powder groups decreased （P＜0.05）. ConclusionRunmu Xiaoyao Powder can negatively regulate the IRAK1/TRAF6/NF-κB signalling pathway in the cornea and lacrimal gland of mice with dry eye of liver-meridian constraint-heat syndrome by up-regulation of miR-146a-5p， so as to inhibit inflammatory response and reduce the damage of the ocular surface tissues， and the high doses group showed the best effect.