OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Background Metals and metalloids in fine particulate matter (PM_2.5) may cause damage to the respiratory and circulatory systems of the human body, and long-term exposure is prone to causing chronic poisoning, cancer, and other adverse effects. Objective To assess the distribution characteristics of metals and metalloids in outdoor PM_2.5 in a southern city of China, conduct source apportionment, and evaluate the associated health risks, thereby providing theoretical support for further pollution control measures. Methods PM_2.5 samples were collected in districts A, B, and C of a southern China city, and the concentrations of 17 metals and metalloids were detected by inductively coupled plasma-mass spectrometry (ICP-MS). Pollution sources were assessed through enrichment factor and principal components analysis, and the main pollution sources were quantified using absolute principal component scores-multivariate linear regression (APCS-MLR). Health risks were evaluated based on the Technical guide for environmental health risk assessment of chemical exposure (WS/T777—2021). Results The ambient air PM_2.5 concentrations in the city were higher in winter and spring, and lower in summer and autumn. The annual average concentrations of ambient PM_2.5 in districts A, B, and C were 36.7, 31.9, and 24.4 μg·m⁻³, respectively. The ambient PM_2.5 levels in districts B and C were below the second-grade limit set by the Ambient air quality standards (GB 3095—2012). The enrichment factors of cadmium (Cd), aluminum (Al), and antimony (Sb) were greater than 10, those of copper (Cu), lead (Pb), arsenic (As), nickel (Ni), mercury (Hg), and molybdenum (Mo) fell between 1 and 10, and those of manganese (Mn), vanadium (V), chromium (Cr), cobalt (Co), barium (Ba), beryllium (Be), and uranium (U) were below or equal to 1. The comprehensive evaluation of source analysis showed that the main pollution sources in districts A and C and the whole city were coal-burning. In district B, the main pollution source was also coal combustion, followed by industrial process sources and dust sources. The carcinogenic risks of As and Cr were between 1×10⁻⁶ and 1×10⁻⁴. However, the hazard quotients for 15 metals and metalloids in terms of non-carcinogenic risk were below 1. Conclusion Cr and As in the atmospheric PM_2.5 of the city present a certain risk of cancer and should be paid attention to. In addition, preventive control measures should be taken against relevant pollution sources such as industrial emission, dust, and coal burning.

AIM: To assess the impact of optimized pulsed technology(OPT)on the morphological and functional changes of meibomian glands in patients with meibomian gland dysfunction(MGD).METHODS: This prospective case-control study enrolled 60 MGD patients(60 right eyes)treated at Weifang Eye Hospital from September 2023 to February 2024. Patients were categorized into mild, moderate, and severe groups based on the extent of meibomian gland loss, with 20 cases(20 eyes)per group. Treatments consisted of bilateral OPT combined with meibomian gland massages, administered biweekly over four sessions. Ocular surface function indicators including the ocular surface disease index(OSDI), corneal fluorescein staining(CFS), non-invasive average tear break-up time(NIBUTav), and non-invasive tear meniscus height(NITMH), as well as meibomian gland function parameters such as meibomian gland expressibility score(MGES)and meibomian gland secretion score(MGYSS)were observed and recorded before treatment and at 3 mo after final treatment. Cellular-level assessments using in vivo confocal microscopy(IVCM)examined meibomian gland acinar unit density(MGAUD), inflammatory cell density(ICD), meibomian gland acinar longest diameter(MGALD)and meibomian gland acinar shortest diameter(MGASD).RESULTS: At baseline, no significant differences were found in NITMH across groups(P>0.05). Statistical significance were observed in NIBUTav, MGES, MGYSS, MGAUD, MGALD, and MGASD(all P<0.05). Compared to the mild group, the moderate and severe groups showed significant differences in OSDI, CFS, and ICD(all P<0.05), though no significant differences existed between moderate and severe groups(all P>0.05). At 3 mo after treatment, all groups showed no significant differences in NITMH(all P>0.05). All parameters improved significantly in the mild group(all P<0.05); all indicators improved in the moderate group(P>0.05), except for MGASD before and after treatment(all P<0.05); significant improvements were noted in OSDI, CFS, and NIBUTav in the severe group(all P<0.05), while MGES and MGYSS did not differ significantly(all P>0.05). IVCM parameters(MGAUD, ICD, MGALD, and MGASD)showed no significant change in the severe group(all P>0.05).CONCLUSION:OPT effectively enhances various ocular surface functions and improves gland expressibility and secretion quality in mild to moderate MGD cases, while also positively impacting certain cellular parameters. In severe cases, where most acinar functions are lost and structural reversibility is limited, OPT can still mitigate MGD symptoms and decelerate disease progression.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.