By systematically reviewing the concept evolution of pre-chronic obstructive pulmonary disease （pre-COPD） and the research status of traditional Chinese medicine （TCM）， as well as considering the clinical practice， this paper puts forward the strategies for the prevention and treatment of pre-COPD with TCM. These strategies include identifying high-risk groups by combining TCM syndrome and constitution， advocating the principle of "treating disease before it arises" and promoting the combination of syndrome differentiation and constitution evaluation to achieve individualized intervention， promoting collaboration between TCM and western medicine， supported by digital and intelligent technologies， to establish a whole-process management mode of "hospital-community-family". The aim is to realize the early diagnosis， early intervention and whole-process management of pre-COPD， thereby helping reduce the incidence of COPD.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Chronic obstructive pulmonary disease （COPD） is a common clinical chronic airway disease with high morbidity， high mortality， a heavy disease burden， and complex mechanisms that have not been fully elucidated. Clinical problems promote the continuous progress of basic research. The establishment and evaluation of animal models is an important way to delve into the pathogenesis and treatment strategies of COPD. On the basis of the etiology， pathogenesis， diagnostic criteria， and syndrome differentiation of COPD in traditional Chinese medicine （TCM） and Western medicine， this paper summarizes the establishment methods and characteristics of existing animal models of COPD and analyzes the fitting degree of the models with the disease characteristics in Western medicine and syndrome characteristics in TCM. The results showed that the animal models of COPD in Western medicine were mainly induced by single factors and compound factors， and the model with the highest fitting degree was established by cigarette smoke combined with lipopolysaccharide and hormone. The model showed a fitting degree of 84% with the disease characteristics in Western medicine and 70% with the syndrome characteristics in TCM， being consistent with the clinical characteristics of COPD induced by multiple factors. Most of the animal models of COPD in TCM were established on the basis of disease models and combined with TCM etiology and pathogenesis characteristics， and prepared by syndrome differentiation. Among them， the model of accumulation of cold and water retention in lung had the highest fitting degree of 92% with the TCM diagnostic criteria. The models of phlegm-heat obstructing lung and phlegm-stasis obstructing lung had the fitting degree of 94% with clinical manifestations in Western medicine and the highest fitting degree with the diagnostic criteria in Western medicine. Different animal models of COPD have their own advantages and disadvantages， and most of them simply replicate the manifestations of COPD at a certain stage， failing to reflect the multiple causes and the dynamic changes of TCM etiology and pathogenesis. Moreover， the syndromes of these models fail to match the clinical syndromes in TCM. Therefore， establishing the animal models reflecting clinical characteristics of COPD in TCM and Western medicine and improving the model evaluation criteria are important contents to promote the overall development of integrated traditional Chinese and western medicine for COPD.

Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P＜0.0001),BBB disruption(P＜0.0001),impairment in learning skills and memory(P＜0.001),and anxiety/depression-like behaviors(P＜0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P＜0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P＜0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P＜0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P＜0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P＜0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

Objective:In this study, the role of IL-17 in the pathogenesis of idiopathic myositis (IIM) was preliminarily investigated by detecting the expression of IL-17 in the muscle tissues of patients with idiopathic inflammatory myositis (IIM) and normal controls.Methods:Twenty-eight patients (20 in DM group with dermatomyositis and 8 in ASS group with anti-synthase syndrome) who were diagnosed with IIM after muscle biopsy and autoantibody detection in our hospital for the first time from October 2019 to August 2021 were included. Twelve cases with normal muscle tissue matched for age and sex were included as the control group. Western blot and immunohistochemical techniques were used to detect the expression level of IL-17 in muscle tissue, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum IL-6. Mann-Whitney U rank sum test was used to compare the difference of IL-17 expression in muscle tissue between the two groups, and non-parametric test was used for comparison between multiple groups. Chi-square test and Spearman rank correlation analysis were used, and P<0.05 was considered statistically significant. Results:① The expression level of IL-17 in IIM muscle tissue[1.63(1.30, 2.05)pg/ml was higher than that in control group[1.00(0.96, 1.00)pg/ml, and the difference was statistically significant ( Z=-3.52, P<0.001). The difference be-tween DM[1.94(1.58, 2.14)pg/ml] and ASS[1.22(1.04,1.55)pg/ml was statistically significant ( Z=-3.20, P=0.001). ② Compared with healthy control group [4.08(3.01, 5.67)pg/ml, the expression of IL-6 in ⅡM serum[8.88(4.93, 13.64) was high ( Z=-3.01, P=0.003), which was positively correlated with the expression of IL-17 ( r=0.42, P=0.027). ③ The ex-pression of IL-17 in muscle tissue was higher in IIM associated with muscle weakness[1.91(1.56, 2.14) pg/ml vs 1.50(1.04, 2.00)pg/ml] ( Z=-1.38, P=0.020), dysphagia [2.06(1.99, 2.14)pg/ml vs 1.62(1.52, 2.04)pg/ml] ( Z=-2.74, P=0.010) and skin involvement[1.98(1.57, 2.14)pg/ml vs 1.04(0.86, 1.61)pg/ml] ( Z=-3.20, P<0.010), and the differences were statistically significant ( P<0.05). ④IL-17 was positively correlated with Myoact-total activity ( r=0.51, P=0.006), Myoact-muscle symptom ( r=0.45, P=0.016), erythrocyte sedimen tation ( r=0.48, P=0.020), and myoenzyme increase ( r=0.56, P=0.002). Conclusion:IL-17 and IL-6 are synergistically involved in the pathogenesis of IIM, suggesting that IL-17 is the therapeutic target of IIM.

Objective To evaluate the efficacy and safety of tip-flexible ureterorenoscope (tf-URS) with holmium laser for one-stage management of parapelvic cyst.Methods The clinical data of 26 patients treated with tf-URS incision and drainage using holmium laser from February 2016 to August 2018 were reviewed.The study were including 15 male and 11 female patients,ranging from 32 to 68 years old,with an average of 53.5 years old.There were 24 cases of unilateral single renal parapelvic cyst and 2 cases of bilateral single renal parapelvic cyst.There were 4 cases in 26 cases with unilateral single renal parapelvic cyst and contralateral single renal cyst,2 cases with unilateral single renal parapelvic cyst and ipsilateral kidney of stones.The diameter of parapelvic cyst was 3.4-5.6 cm,average 4.8 cm.All patients had undergone holmium laser endo-decortication of parapelvic cyst by tf-URS.With general anesthesia,tf-URS accessed pelvis retrogradely and decorticated parapelvic cyst with 200 μm Holium laser to drainage the cyst to pelvis.If the tf-URS was not placed successfully for the first time,Double-J tubes were retained for 1-2 weeks before treatment.The operative time,hospitalization time,blood loss,postoperative complications and clinical symptoms were collected and analyzed.Results The one-time access success rate of insertion of ff-URS was 88.5％ (23/26).All operations were successful without severe complications.The average time of operation was 17.2 min,ranging from 11 to 25 min.In 3-30 months follow-up,the cysts disappeared in 22 patients and reduced by more than one half in 1 patients.Flank pain relieved in 19 patients.Conclusions Holmium laser endo-decortication of parapelvic cyst by tf-URS could be a simple,minimally invasive,safe and effective method for parapelvic cyst,which is worthy of further promotion and application in clinical practice.

Objective To evaluate the efficacy and safety of transurethral laser shovel type vaporresection-enucleation of the prostate (LS-VREP) based on the inter-layer of surgical capsule for the treatment of benign prostatic hyperplasia (BPH),which was less 80 g weight.Methods From September 2013 to August 2016,a retrospective study was performed including 1 369 cases of BPH patients,who were treated by 120-160 W transurethral laser (straight green-light) shovel type vapor-resection-enucleation of the prostate (LS-VREP group,n =1 008) and transurethral resection of the prostate (TURP group,n =361).The preoperative data,including average age,prostate weight,IPSS,QOL,Qmax and PVR was reviewed.There was no significant difference of the above data between the two groups (P ＞ 0.05).Operative time,changes of hemoglobin and serum sodium concentration,postoperative bladder irrigation time,catheter indwelling duration,hospital stay,pre-and 3 months post-operative IPSS,QOL,Q PVR were recorded.In addition,complications were monitored.Results Mean operation time of LS-VREP group was (46.1 ± 18.6) min,while TURP group was (48.2 ± 15.2) min,and there was no difference between the two groups (P ＞ 0.05).Post-operative mean hemoglobin concentration and serum sodium concentration of LS-VREP group decreased (1.6 ± 1.2) g/L and (1.2 ± 0.6) mmol/L respectively,while those of TURP group decreased (5.7 ± 3.6) g/L and (3.2 ± 1.2) mmol/L,and the differences were statistically significant (P ＜ 0.05).Mean post-operative catheter indwelling time,and post-operative hospital stay of LS-VREP group was (42.9 ± 12.7) h and (3.2 ± 0.6) d,while TURP group was (65.7 ± 15.4) h and (5.4 ± 1.2) d,and the differences were statistically significant (P ＜ 0.05).Comparatively IPSS,QOL,Qmax and PVR were all improved significantly in both groups at 3 months after operation (P ＜ 0.05),but no significant difference was found between the two groups (P ＞ 0.05).After three months' follow-up of post-operation,as for the complication rate,including TURS,bleeding requiring reoperation,incontinence,dysuria and erectile dysfunction,LS-VREP group (15/1 008) was less than that of TURP group (30/361,P ＜ 0.05).Conclusions The LS-VREP based on the inter-layer of surgical capsule is safe and effective for the treatment of BPH patients whose prostate weight was less than 80 g.LS-VREP showed less intraoperative bleeding,faster postoperative recovery,and high safety,which is considered a safe,effective and optimized minimally invasive surgery.

Objective To evaluate the safety and efficacy of transurethral frontfiring photoselective vaporesection for the treatment of cystitis glandularis,by comparing with the transurethral bipolar plasmakinetic resection.Methods From January 2014 to July 2016,41 patients with pathologically diagnosed cystitis glandularis in our hospital,were divided into two groups,including 22 cases underwent transurethral frontfiring photoselective vaporesection(the observation group),and the other 19 cases underwent transurethral bipolar plasmakinetic resection(the control group).All patients were regularly treated with postoperative intravesical instillation chemotherapy with pirarubicin.The clinical data of two groups were statistically analyzed to compare the differences of the safety and efficacy.Results All the surgeries were performed successfully.There were no statistical significances in perioperative data,the operation time,the decreased concentration of hemoglobin(Hb)and Na+,operative related complications, indwelling catheter duration and hospitalization duration between the two groups.The first-time cure rate and the effective rate of transurethral frontfiring photoselective vaporesection showed significantly better than those of transurethral bipolar plasmakinetic resection(P<0.05 for each).Conclusion Comparing the traditional transurethral bipolar plasmakinetic resection for the treatment of cystitis glandularis,tansurethral frontfiring photoselective vaporesection with postoperative intravesical instillation chemotherapy with pirarubicin,is a safer,simpler,and more effective method,which could be a new optional method in the conditional hospitals,deserving the worthy of clinical popularization.