Dry eye （DE） is a prevalent multifactorial disease of the ocular surface， clinically characterized by tear film homeostasis imbalance accompanied by related ocular surface symptoms. Specifically， the tear film is a thin liquid layer of tears covering the cornea and conjunctiva through blinking， while tear film homeostasis serves as the foundation for maintaining normal ocular surface structure and function. Insufficient tear secretion and excessive tear film evaporation lead to tear hyperosmolarity and the production of inflammatory mediators， disrupting tear film homeostasis and subsequently forming DE. Additionally， cascade reactions are triggered， resulting in a "vicious cycle of DE" that exacerbates the disease severity and prolongs its duration. Therefore， for DE treatment， it is crucial to restore tear film homeostasis and terminate this vicious cycle. Traditional Chinese medicine （TCM）， which differentiates and treats DE based on systemic conditions， often achieves favorable therapeutic outcomes， offering additional treatment options for DE. Studies have demonstrated that TCM can alleviate DE by regulating tear film homeostasis and terminating the vicious cycle. This review systematically summarizes recent basic experimental research in China and abroad on TCM in alleviating DE by regulating tear film homeostasis， aiming to provide a theoretical basis for clinical treatment and an insight for research design.

ObjectiveTo compare the differences in color， odor， coumarin content and microbial community composition of Angelicae Dahuricae Radix（ADR） during different drying processes， and to explore the correlation between changes in microbial community composition and changes in quality indexes of ADR. MethodsThe fresh ADR was processed at three drying temperatures（50， 70， 100 ℃） by drying and steaming cutting， semi-fresh cutting and drying， fresh cutting and drying， and sulfur fumigation methods. The color values of samples were extracted by Adobe Photoshop 2022 software and subjected to principal component analysis（PCA）， electronic nose was used to identify the odor information of medicinal powders and subjected to loadings analysis， PCA， and linear discriminant analysis（LDA）， and high performance liquid chromatography（HPLC） was used to determine the contents of five coumarins（bergapten， oxypeucedanin， imperatorin， phellopterin， isoimperatorin）. The samples for microbial detection were taken from fresh dried samples， 50 ℃（dried and steamed cut， sulfur fumigated） samples， and 100 ℃（dried and steamed cut） samples when the water content was 50% and 14%， respectively. And the changes of microbial community composition during processing were determined by high-throughput sequencing method. The relationship between the changes of microbial community composition and the changes of odor， color and active component content of ADR during drying process was analyzed by Pearson correlation analysis. ResultsThe color quantification results showed that an increase in drying temperature led to the decrease of brightness value（L）， and the increases of red-green value（a） and yellow-blue value（b）， and the change of processing method had no obvious effect on the color of medicinal materials. The results of odor quantification showed that W1S， W2S， W5S， W2W and W1W sensor were sensitive to the odor changes of ADR and could be used to distinguish ADR decoction pieces from different processing methods. The results of HPLC showed that the coumarin content of ADR decreased with the increase of drying temperature and the delay of processing time， the optimal processing method was drying and steaming cutting method， and the optimal temperature was 50 ℃. High-throughput sequencing results showed that the dominant bacteria in ADR during processing were Achromobacter， Agrobacterium， Nocardioides， Mycobacterium and Enterobacter， the dominant fungi were Coprinopsis， Meyerozyma and Apiotrichum. The results of correlation analysis showed that the quality indexes of ADR were positively correlated with Agrobacterium， Mycobacterium in bacteria， Candida in fungi， and negatively correlated with Bacillus in bacteria. ConclusionThere are significant differences in the color， odor， coumarin content and microbial community composition of ADR in different drying processes， and the best drying method is drying and steaming cutting at 50 ℃. The relative abundance changes of 9 bacterial genera and 4 fungal genera are closely related to the quality formation of ADR during the drying process.

AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

[Purpose]To analyze the incidence and mortality of pancreatic cancer in 2020 and the change trend from 2010 to 2020 in cancer registration areas of Gansu Province.[Methods]The data of pancreatic cancer from 2010 to 2020 were collected from cancer registries in Gansu Province.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate and proportion of pancreatic cancer were calculated.Joinpoint 4.7.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC of pancreatic cancer in cancer registration areas of Gansu Province from 2010 to 2020.[Results]In 2020,a total of 838 new cases of pancreatic cancer were reported in the cancer registration areas of Gansu Province,with a crude incidence rate of 6.52/105,ASIRC and ASIRW of 4.03/105 and 4.49/105 respectively,accounting for 2.50％of all malignant tumor incidence.In 2020,702 cases of pan-creatic cancer deaths were reported in the cancer registration areas of Gansu Province,with a crude mortality rate of 5.46/105,ASMRC and ASMRW of 3.25/105 and 3.73/105,respectively,ac-counting for 3.98％of all malignant tumor deaths.From 2010 to 2020,a total of 2 413 cases of pancreatic cancer were reported in cancer registration areas in Gansu Province,accounting for 1.90％of all malignant tumors in the province.The crude incidence rate of pancreatic cancer was 5.28/105,the ASIRC was 4.18/105,the ASIRW was 4.63/105,and the cumulative rate of 0～74 years old was 0.49％.From 2010 to 2020,a total of 1 871 pancreatic cancer deaths were reported in cancer registration areas of Gansu Province,accounting for 2.38％of all malignant tumor deaths in the province.The crude mortality rate was 3.92/105,the ASMRC was 3.09/105,the ASMRW was 3.50/105,and the cumulative rate of 0～74 years old was 0.36％.In terms of sex and region,the incidence and mortality of pancreatic cancer from 2010 to 2020 in men were higher than those in women,and higher in rural areas than those in urban areas.From 2010 to 2020,the incidence and mortality were at a low level under the age of 44 years old,and increased significantly after 45 years old,reaching a peak in the age group of 80～84 years old.ASIRC showed no significant change from 2010 to 2020 with an AAPC of 0.41 1％(P＞0.05).From 2010 to 2020,the ASMRC showed an significantly increasing trend with an AAPC of 6.515％(P=0.014).[Conclusion]From 2010 to 2020,the ASRIC of pancreatic cancer in Gansu Province showed no significant change,while the ASMRC showed a significantly in-creasing trend.The incidence and mortality rates were higher in men than those in women and higher in rural areas than those in urban areas.Middle-aged and elderly men in rural areas are the key groups of prevention and treatment of pancreatic cancer,so targeted prevention and control measures should be carried out.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective To investigate the kinematic patterns of gate-turning techniques in sitting alpine skiing at the Winter Paralympic Games and their impacts on skiing performance.Methods Using drone footage and inertial sensor technology,kinematic data were collected from 11 alpine sit-skiers preparing for the Winter Paralympics.Key technical indicators such as turning radius,skiing speed,and trajectory length were analyzed for their relationship with skiing performance.Results The minimum turning radius during gate turns was(15.80±3.55)m,and turning radius showed a significant positive correlation with skiing time(r=0.40,P=0.02)and trajectory length(r=0.88,P＜0.01).The maximum skiing speed was(16.92±1.60)m/s,which was strongly negatively correlated with total skiing time(P＜0.01).Exit speed was also significantly positively correlated with total skiing distance(P＜0.05).Additionally,single-gate technical characteristics(such as turning radius and speed variation),were strongly reflective of overall skiing performance.Conclusions Optimizing turning radius and minimizing speed loss are critical for improving skiing efficiency.Single-gate kinematic analysis provides a scientific basis for overall technique optimization and offers valuable guidance for training and competition strategy design.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

AIM:To investigate the roles of up-regulated inwardly rectifier potassium channel 2.1(Kir2.1)in macrophage activation and cardiac inflammatory injury,in order to clarify the mechanism of Kir2.1 regulation in inflam-matory injury and cardiac repair.METHODS:The RAW264.7 macrophages were activated by lipopolysacharide(LPS)and treated with Kir2.1 agonist zacopride or lentivirus-Kir2.1 overexpression(Kir2.1-OE).Macrophages were randomly divided into control,LPS,LPS+zacopride(or LPS+Kir2.1-OE),and LPS+zacopride+BaCl2 groups.The effects of Kir2.1-OE and AG490[Janus kinase 2(JAK2)inhibitor]on the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway in macrophages were also investigated.The expression of CD86,interleukin-6(IL-6)and Kir2.1 in M1 macrophages was detected by RT-qPCR or immunofluorescence staining.The expression of JAK2/STAT3 molecules was detected by Western blot.The RAW264.7 macrophages were incubated with LPS,LPS+zacopride or LPS+zacopride+BaCl2 for 12 h,and then co-cultured with H9C2(2-1)cardiomyocytes for 48 h.The expression of Kir2.1,IL-4,IL-6,IL-1β,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,calcium/calmodulin-dependent protein kinase II(CaMKII)and p-CaMKII in cardiomyocytes was detected by Western blot.We fur-ther compared the effects of zacopride and KN-93,a known CaMKII inhibitor,on cardiac CaMKII.After being incubated with LPS for 12 h and changed the medium,RAW264.7 macrophages were co-cultured with H9C2(2-1)cardiomyocytes which was pretreated with KN-93.The cardiomyocytes were divided into control,LPS,and LPS+KN-93 groups.The ex-pression of CaMKII and p-CaMKII were detected by Western blot.RESULTS:Zacopride inhibited LPS-induced M1-type polarization of macrophages in a Kir2.1-dependent manner as showed by a significant decrease in CD86(M1-type marker)and IL-6(P<0.05).Zacopride or Kir2.1-OE inhibited LPS-induced activation of JAK2/STAT3 inflammatory signaling pathway in macrophages,with effects similar to the JAK2 inhibitor AG490.The H9C2(2-1)cardiomyocytes were co-cul-tured with M1-polarized macrophages(P<0.05).Zacopride inhibited M1 macrophage-induced inflammatory injury in car-diomyocytes,which was manifested as decreased expression of IL-1β and IL-6,increased expression of IL-4,and de-creased apoptosis.Zacopride also inhibited activation of CaMKII in a Kir2.1-dependent manner in H9C2(2-1)cells co-cultured with macrophages(P<0.05).CONCLUSION:Up-regulation of Kir2.1 may inhibit LPS-induced M1-type polar-ization of macrophages via inhibiting JAK2/STAT3 signaling pathway.Up-regulation of macrophage Kir2.1 may play a pro-tective role in cardiac repair after myocardial infarction by negative regulation of CaMKII signaling.

Aim To investigate the effect of hypobaric hypoxia on macrophage necroptosis and atherosclerotic plaque instability and explore the underlying mechanisms.Methods Mouse bone marrow-derived macrophages were i-solated and cultured,and divided into control group(21％oxygen concentration)and hypoxia group(3％oxygen concen-tration).After 48 hours,cell necroptosis was detected,and the expression of cell necroptosis related proteins was deter-mined by Western blot.Healthy male ApoE-/-mice were randomly divided into control group and hypobaric hypoxia group.After the intervention for 16 weeks,the plasma lipids and inflammatory cytokines were measured,the areas of ath-erosclerotic plaque and necrotic core were evaluated by HE staining.The content of plaque collagen was detected by Mas-son staining.The number of macrophages in the plaque and the expression of necrotic apoptosis related proteins were de-tected by immunohistochemical staining and Western blot.Results Hypoxia induced increased necrotic apoptosis of macrophages(P＜0.01),while necroptotic inhibitor necrostatin-1(Nec-1)reduced hypoxia induced cell death(P＜0.05);hypoxia leads to a decrease in the expression of adenosine deaminase acting on RNA 1(ADAR1)in macrophages(P＜0.01),and an increase in the expression of Z-DNA binding protein 1(ZBP1),phosphorylated receptor-interacting serine/threonine-protein kinase(p-RIPK3),and phosphorylated mixed lineage kinase domain-like protein(p-MLKL)(all P＜0.01).Compared with the control group,the plasma lipid levels of ApoE-/-mice in the hypobaric hypoxia group did not change significantly(P＞0.05),the plasma inflammatory cytokines(TNF-α,IL-1β,IL-6 and MCP-1)increased(all P＜0.05),the area of atherosclerotic plaque increased(P＜0.05),the area of plaque necrotic core increased,the content of plaque collagen decreased,the number of macrophages increased,the expression of ADAR1 decreased,and the expres-sion of ZBP1 and p-MLKL increased(all P＜0.01).Conclusion Hypobaric hypoxia causes the imbalance of A-DAR1/ZBP1 expression in macrophages,activates RIPK3/MLKL signaling pathway,promotes macrophage necroptosis,in-creases the area of plaque necrosis core,and leads to increase instability of atherosclerotic plaque.