BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

Objective: To explore the interaction of multi-target stool DNA (MT-sDNA), intestinal flora and environmental factors in the development of colorectal cancer, so as to provide insights into pathogenesis study of colorectal cancer. Methods: A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were included in the case group and 51 healthy subjects were included in the control group. Demographic information, diet and family history of colorectal cancer were collected by a questionnaire survey. MT-sDNA, intestinal flora, cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and other tumor markers were detected. Interactions of MT-sDNA, intestinal flora and environmental factors with the development of colorectal cancer was analyzed by multifactor dimensionality reduction (MDR), crossover analysis and additive model. Results: The case group included 20 males (37.04%) and 34 females (62.96%), and had a mean age of (64.89±9.72) years. The control group included 24 males (47.06%) and 27 females (52.94%), and had a mean age of (53.94±10.33) years. MDR analysis showed that subjects with both high absolute intestinal flora indexes and positive MT-sDNA had an increased risk of colorectal cancer (OR=3.782, 95%CI: 1.190-5.034). Crossover analysis showed that subjects with positive MT-sDNA and >5 μg/L of CEA had an increased risk of colorectal cancer (OR=2.121, 95%CI: 1.162-4.033). Additive model analysis showed that MT-sDNA had positive additive interaction with CEA (SI=3.687, 95%CI: 1.229-7.238), and MT-sDNA had negative additive interaction with fruit intake (SI=0.145, 95%CI: 0.020-0.753). Conclusion Positive MT-sDNA can synergistically increase the risk of colorectal cancer with high intestinal flora index and CEA, and fruit intake can reduce the risk of colorectal cancer in MT-sDNA-positive population.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

ObjectiveTo investigate the pharmacodynamics， pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide（LPS）-induced depression rats. MethodRats were randomly divided into the control group， model group， fluoxetine group（10 mg·kg^-1）， Jiaotaiwan group（1.5 g·kg^-1） and combination group（1.5 g·kg^-1 of Jiaotaiwan+0.05 g·kg^-1 of borneol）， with 8 rats in each group. Except for the control group， the depression model was established by intraperitoneal injection of LPS for 7 consecutive days， and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors［interleukin-1β（IL-1β）， IL-6 and tumor necrosis factor-α（TNF-α）］ of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin（HE） and Nissl staining. After the behavioral tests of sucrose preference， open field and forced swimming were completed， blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage， the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed， and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group， rats in the model group showed decreased sucrose preference rate and total distance of open field， prolonged swimming immobility time， and increased expression of inflammatory factors in serum（P<0.01）. Compared with the model group， the sucrose preference rate and total distance of open field were increased， and the swimming immobility time was shortened in the rats of each administration group， and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group（P<0.05， P<0.01）. The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group， the area under the curve（AUC_0-t， AUC_0-∞）， peak concentration（C_max） and the average steady-state plasma concentration（C_av） of berberine and epiberberine in the combination group were increased（P<0.05， P<0.01）， AUC_0-t， AUC_0-∞， mean residence time（MRT_0-∞） and C_av of coptisine were significantly increased（P<0.05， P<0.01）， C_max of jatrorrhizine increased significantly（P<0.05）， but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group， the contents of jatrorrhizine， epiberberine， coptisine， palmatine and berberine in the brain tissue of combination group were increased（P<0.05， P<0.01）， the content of magnoflorine increased and that of berberrubine decreased， but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats， reduce the levels of serum inflammatory factors， improve the pathological damage of hippocampus， and have antidepressant effect. Compared with Jiaotaiwan alone， the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats， improve its bioavailability， promote its absorption， and improve the brain targeting of the drug， which is more conducive to the antidepressant effect of Jiaotaiwan.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

{L-End}Objective To investigate the effect of motorcycle exhaust (ME) on the level of oxidative stress in different parts of respiratory tract epithelial cells. {L-End}Methods BEAS-2B and A549 cells in logarithmic growth phase were randomly divided into control group, low- and high-dose groups. The two kinds of cells growing on the membrane of Transwell inserts were treated with air-liquid interface (ALI) exposure technique for 60 minutes. The cells in the low- and high- dose groups were treated with diluted gas with the volume ratio of ME to clean air of 1∶20 and 1∶10, respectively, while the cells in the control group were treated with clean air. Cells were collected to detect their relative survival rate using CCK-8 method after exposure. And the levels of malondialdehyde, glutathione and the activity of superoxide dismutase (SOD) of the cells were detected using colorimetry. {L-End}Results The ME exposure dose affected the relative survival rate of cells (P<0.01), which showed a downward trend with the increasing ME exposure doses (all P<0.05). However, there was no significant difference in the main effect of cell types and the interaction effect of ME exposure dose and cell type (all P>0.05). There was a significant interaction between ME exposure dose and cell type in the level of glutathione and the activity of SOD (all P<0.01), and the level of malondialdehyde was a significant main effect of cell type (P<0.01). There was no significant difference in the glutathione level and SOD activity between the low-dose group and the control group (all P>0.05), while the glutathione level and SOD activity in high-dose group were higher than those in the control group and low-dose group in BEAS-2B cells (all P<0.05). The glutathione level decreased with increasing ME exposure dose in A549 cells (all P<0.05). Compared with the control group, the low-dose group had a significantly higher activity of SOD (P<0.05) in A549 cells. The SOD activity of A549 cells in high-dose group was lower than those in control group and low-dose group (all P<0.05). The level of malondialdehyde in A549 cells was higher than those in BEAS-2B cells(P<0.05). {L-End}Conclusion ME exposure can lead to changes in the production of oxidative stress biomarkers in respiratory tract epithelial cells. The oxidative stress response induced by ME exposure varies among respiratory tract epithelial cells from different regions.