ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

Objective:To explored the correlation between anxiety and depression and cerebral small vessel disease(CSVD)in the elderly patients with type 2 diabetes mellitus(T2DM), and analyzed the influencing factors of anxiety and depression.Methods:Clinical data of 101 elderly T2DM inpatients admitted to the Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University from July 2020 to December 2021 were retrospectively analyzed, and clinical features, laboratory tests and examination data were collected.The Hamilton Depression Scale and the Hamilton Anxiety Scale were used for assessment, with a cut-off value of 14 points for anxiety and 8 points for depression.Brain scans were performed using 3.0T magnetic resonance scanner, including T1WI sequence, T2WI sequence, 3D-FLAIR sequence, SWI sequence.According to the total MRI load scoring standard of CSVD proposed by Staals, MRI imaging changes of CSVD, namely lacunar foci(LIs), cerebral microhemorrhage(CMBs), perivascular space(PVSs), and white matter high signal(WMHs), were analyzed and scored respectively.Load score ≥1 was defined as CSVD group.According to the above criteria, the enrolled patients were divided into depression group and anxiety group, and the clinical characteristics, biochemical test data and MRI imaging characteristics of CSVD between the two groups were analyzed by single factor analysis, and then Spearman correlation analysis was used to analyze the related factors of the elderly T2DM with anxiety and depression.Binary logistic analysis was used to analyze the risk factors of depression and anxiety in the elderly patients with T2DM.Results:Compared with the non-depressed group, the elderly T2DM patients with depression were older, more female, and the incidence of WMHs and DWMHs was higher( P<0.05).Compared with the non-anxious group, the incidence of WMHs and DWMHs in the elderly T2DM patients with anxiety group was higher( P<0.05).Spearman correlation analysis showed that age( r=0.224, P=0.024), WMHs( r=0.231, P=0.020), PWMHs( r=0.201, P=0.044), DWMHs( r=0.274, P=0.006)was positively correlated with depression in the elderly T2DM, while gender( r=-0.225, P=0.024)、ALT( r=-0.208, P=0.037)、AST( r=-0.204, P=0.041)was negatively correlated with depression in the elderly T2DM.WMHs( r=0.213, P=0.033)and DWMHs( r=0.270, P=0.006)were positively correlated with anxiety in the elderly T2DM.Binary logistic regression analysis showed that gender( OR=0.359, 95% CI: 0.130-0.990, P=0.048), DWMHs(OR=4.373, 95% CI: 1.290-14.828, P=0.018)were the influencing factors for the elderly T2DM patients with depression, and DWMHs( OR=5.000, 95% CI: 1.444-17.317, P=0.011)was the influencing factors for the elderly T2DM patients with anxiety. Conclusions:DWMHs is closely related to the onset of depression and anxiety in the elderly T2DM patients, suggesting that CSVD may be involved in the development of depression and anxiety in the elderly T2DM patients.

[Objective]To investigate the chemical compositions,antioxidant and anti-inflammatory activities of Jiangshan Polygonatum sibiricum alcoholic extract(PSAE)in vitro.[Methods]The chemical compositions of PSAE were identified by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MSE),its antioxidant activity was studied,and in vitro experiments were conducted to determine its effect on lipopolysaccharide(LPS)-induced THP-1 cells.Molecular docking was further used to validate the results.[Results]PSAE contained 17 chemical compositions,including 5 flavonoids,5 saponins,3 lignans,1 phenolic acid,1 steroid and 2 other compositions.In vitro experiments showed that PSAE possessed great antioxidant activity.Besides,PSAE could increase the viability of LPS-induced THP-1 cells,significantly decrease the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in cell supernatants and the expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl aspartate specific proteinase-1(Caspase-1).Molecular docking results showed that 16 of the 17 chemical compositions detected in PSAE had good docking activities with the core targets of NLRP3,ASC and Caspase-1.[Conclusion]PSAE has great antioxidant and anti-inflammatory activities,and the main active compositions may be flavonoids and saponins.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

OBJECTIVETo assess the efficacy and safety of modified ligation of the intersphincteric fistula tract for simple transsphincteric perianal fistula.

METHODSSeventy patients with simple transsphincteric perianal fistula between October 2012 and January 2014 in our department were prospectively enrolled. According to the random number table, patients were divided into two groups: modified-LIFT group (37 cases, from the external opening close to the fistula, dissect the external sphincter fistula to the intersphincteric groove by tunneling technique, resect the lateral free fistula) and LIFT group (33 cases). Clinical parametres before and after operation were compared, and results of pelvic electromyogram (EMG) and anorectal manometry three months after operation were analyzed to evaluated anal function.

RESULTSThe operative time, pain score, hospital stay, and healing time were not significantly different between the two groups (all P>0.05). During the median follow-up of 12 months (3-20 months), the healing rate in modified-LIFT group was 83.8% (31/37), which was significantly higher than 60% (20/33) in LIFT group (P=0.029). After operation, 4 patients had persistent unhealed wound, 2 recurred in modified-LIFT group, while 8 patients had persistent unhealed wound, and 5 recurred in LIFT group. No patients developed anal incontinence. By the pelvic EMG and anorectal manometry 3 months after operation, the duration of motor unit potential, occurrence of simple phase, mean resting pressure and maximun squeeze pressure were not significantly different.

CONCLUSIONModified-LIFT procedure for the management of simple transsphincteric perianal fistulas is a simple and effective operation with higher healing rate and similar anal function as LIFT.

Anus Diseases ; surgery ; Humans ; Ligation ; Operative Time ; Pelvis ; Pressure ; Rectal Fistula ; surgery ; Recurrence ; Treatment Outcome ; Wound Healing

Objective To assess the efficacy and safety of modified ligation of the intersphincteric fistula tract for simple transsphincteric perianal fistula. Methods Seventy patients with simple transsphincteric perianal fistula between October 2012 and January 2014 in our department were prospectively enrolled. According to the random number table , patients were divided into two groups:modified-LIFT group (37 cases, from the external opening close to the fistula, dissect the external sphincter fistula to the intersphincteric groove by tunneling technique, resect the lateral free fistula) and LIFT group (33 cases). Clinical parametres before and after operation were compared, and results of pelvic electromyogram (EMG) and anorectal manometry three months after operation were analyzed to evaluated anal function. Results The operative time, pain score, hospital stay, and healing time were not significantly different between the two groups (all P>0.05). During the median follow-up of 12 months ( 3-20 months ) , the healing rate in modified-LIFT group was 83 . 8%( 31/37 ) , which was significantly higher than 60%(20/33) in LIFT group (P=0.029). After operation, 4 patients had persistent unhealed wound, 2 recurred in modified-LIFT group, while 8 patients had persistent unhealed wound, and 5 recurred in LIFT group. No patients developed anal incontinence. By the pelvic EMG and anorectal manometry 3 months after operation, the duration of motor unit potential, occurrence of simple phase, mean resting pressure and maximun squeeze pressure were not significantly different. Conclusion Modified-LIFT procedure for the management of simple transsphincteric perianal fistulas is a simple and effective operation with higher healing rate and similar anal function as LIFT.

Objective To assess the efficacy and safety of modified ligation of the intersphincteric fistula tract for simple transsphincteric perianal fistula. Methods Seventy patients with simple transsphincteric perianal fistula between October 2012 and January 2014 in our department were prospectively enrolled. According to the random number table , patients were divided into two groups:modified-LIFT group (37 cases, from the external opening close to the fistula, dissect the external sphincter fistula to the intersphincteric groove by tunneling technique, resect the lateral free fistula) and LIFT group (33 cases). Clinical parametres before and after operation were compared, and results of pelvic electromyogram (EMG) and anorectal manometry three months after operation were analyzed to evaluated anal function. Results The operative time, pain score, hospital stay, and healing time were not significantly different between the two groups (all P>0.05). During the median follow-up of 12 months ( 3-20 months ) , the healing rate in modified-LIFT group was 83 . 8%( 31/37 ) , which was significantly higher than 60%(20/33) in LIFT group (P=0.029). After operation, 4 patients had persistent unhealed wound, 2 recurred in modified-LIFT group, while 8 patients had persistent unhealed wound, and 5 recurred in LIFT group. No patients developed anal incontinence. By the pelvic EMG and anorectal manometry 3 months after operation, the duration of motor unit potential, occurrence of simple phase, mean resting pressure and maximun squeeze pressure were not significantly different. Conclusion Modified-LIFT procedure for the management of simple transsphincteric perianal fistulas is a simple and effective operation with higher healing rate and similar anal function as LIFT.

Objective To investigate the effect of rosmarinic acid on the behavioral changes in enhanced single prolonged stress (ESPS) model rats and the levels of interlukin-1β (IL-1β) and interlukin-6 (IL-6) in the hippocampus.Methods 48 adult male Sprague Dawley rats were randomly divided into six groups (n =8):Control group,Control + RA (L) group,Control + RA (H) group,ESPS group,ESPS + RA (L) group and ESPS + RA (H) group.Behavioral changes of these rats were analyzed by open field test and elevated plus-maze.The levels of IL-1 β and IL-6 were measured by enzyme linked immunosorbent assay (ELISA).Results (1) Open field test showed that the number of central region entering and the fraction of time exploring in center of ESPS group were significantly reduced than that of Control group ((18.13 ± 10.15) times,(26.68 ± 10.06) ％) and ESPS + RA (H) group ((16.88 ± 8.81) times,(25.08 ± 8.52) ％) (P ＜ 0.05).And it showed no significant difference among Control + RA(L) group,Control + RA(H) group and Control group.Meanwhile,there was also no statistic difference between ESPS group and ESPS + RA(L) group.(2) Elevated plus-maze test showed that percentages of open arm entries and fraction of time exploring in open arm in reference to total number of entries into all arms and total time spent on all arms in ESPS group were significantly reduced than that of Control group((37.38 ± 8.24)％,(17.63 ±4.74)％) and ESPS + RA(H) group((33.72 ±9.49)％,(16.99 ±4.28)％) (P ＜ 0.05),but there was no significant difference between that of ESPS group and ESPS + RA(L) group(P＞0.05).It also showed no significant difference among Control + RA (L) group,Control + RA (H) group and Control group.(3) Compared with ESPS group,RA(10mg/kg) reduced the levels of IL-1β and IL-6 in the hippocampus,but RA(5mg/kg) did not have this effect.(4) Correlation analysis results showed the level of IL-1β in the hippocampus was negatively related with the ameliorated PTSD-like behaviors of ESPS exposure rats.Conclusion RA can ameliorate PTSDlike behaviors of ESPS exposure rats,and this effect may be carried out by down-regulating the levels of IL-1β and IL-6 in the hippocampus,especially the IL-1β.