ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress （CUMS） and explore the mechanism from the histomorphology of frontal cortex， expression of key molecules in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB） signaling pathway， and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups （n=10）： blank control， depression model， Chaihu Shugansan （3.3 g·kg^-1·d^-1）， ferulic acid （50 mg·kg^-1·d^-1）， Chaihu Shugansan （3.3 g·kg^-1·d^-1） + ferulic acid （50 mg·kg^-1·d^-1）， and fluoxetine （2.1 mg·kg^-1·d^-1）. Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used， including fasting with free access to water for 24 h， water deprivation with free access to food for 24 h， wetting the bedding with water in the cage， restraint for 3 h， tail clamping for 1 min， swimming in ice water at 4 ℃， and day and night reversal. Each stimulus was used 1 to 3 times， and the modeling lasted for a total of 21 days. At the same time of stimulation， rats in each medication group were treated with corresponding agents by gavage， while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test， sucrose preference test， and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium， and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF， TrkB， and cyclic adenosine monophosphate-responsive element-binding protein （CREB） in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine （5-HT）， dopamine （DA）， and norepinephrine （NE） in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group， the depression model group showed reduced body mass （P<0.05， P<0.01）， decreased number of crossings and rearings in the open field test and sucrose preference （P<0.01）， prolonged time of immobility in the forced swimming test （P<0.01）， reduced neuronal cells， increased necrotic cells， and darkening cell staining in the frontal cortex， down-regulated mRNA and protein levels of BDNF， TrkB， CREB， and lowered levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Compared with the depression model group， each intervention group showed improved general state， increased body mass （P<0.05）， increased number of crossings （P<0.05）， shortened immobility time in the forced swimming test （P<0.01）， increased neuronal cells， reduced necrotic cells， and lightened cellular staining in the frontal cortex， up-regulated mRNA and protein levels of BDNF， TrkB and CREB， and elevated levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Moreover， the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex （P<0.05）. The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex （P<0.05）， and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test， up-regulating the mRNA levels of BDNF， TrkB， and CREB and the protein levels of BDNF and CREB in the frontal cortex， and increasing the DA content in the frontal cortex （P<0.05）. ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover， the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.

Objective To observe the protective effect of Zhilong Huoxue Tongyu Capsule(Zhilong Capsule)on myocardial ischemia reperfusion injury(MIRI)in mice,and explore its regulatory mechanism using metabolomics.Methods Using a random number table method,30 C57BL/6J mice were randomly divided into the following three groups:sham operation group,model group,and Zhilong Capsule group(6.24 g/kg),with 10 mice in each group.In mice in the model group and the Zhilong Capsule group,a mouse MIRI model was established by ligating the left anterior descending branch,while mice in the sham operation group underwent threading without ligation.The Zhilong Capsule group began modeling one week after pre-administration and continued to receive intragastric administration for two weeks after modeling once daily.The cardiac function,including the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS),was assessed by color echocardiography.The myocardial fibrosis and apoptosis were observed by Masson staining and TUNEL staining,respectively.Enzyme-linked immunosorbent assay was used to measure the serum contents of lactate dehydrogenase(LDH)and brain natriuretic peptide(BNP).Liquid chromatography-mass spectrometry combined with multivariate statistical method was performed for serum metabolite detection and identification analysis.Results Compared with the model group,the mice in the Zhilong Capsule group exhibited an increase in LVEF and LVFS,a reduction in cardiac tissue structure disorder,a decrease in myocardial fibrosis,a decrease in cell apoptosis rate,and a decrease in serum LDH and BNP contents(P<0.05).Metabolomics result showed that intervention with Zhilong Capsule significantly regulated 30 differential metabolites related to MIRI.Important metabolic pathways involved 20 pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.Conclusion Zhilong Capsule has a protective effect on MIRI,and it may achieve this effect by regulating pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.

ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine（TCM） through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects， they were divided into the "1-2 seven" group （under 21 years old）， "3 seven" group （21-27 years old）， "4 seven" group （28-34 years old）， "5 seven" group （35-41 years old）， "6 seven" group （42-48 years old） and "7 seven" and older group （49 years old and above）. The age， average menstrual cycle in the past 3 months， basic hormone levels including follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， testosterone （T） and FSH/LH value， and anti-müllerian hormone （AMH） levels were collected and compared. ResultsA total of 1221 cases were included. The differences in FSH， LH， FSH/LH values， E₂， T， AMH levels and average menstrual cycle among the groups were statistically significant （P＜0.05 or P＜0.01）. AMH peaked in the "3 seven" group. Compared to those in the "3 seven" group， the FSH/LH value in the "4 seven" group increased， while the LH， AMH and T levels decreased， and the menstrual cycle was shortened （P＜0.01）. The FSH/LH， LH， AMH， T and menstrual cycle in the "5 seven" group were consistent with the changing trend of those in the "4 seven" group， while the FSH and E₂ levels in the "5 seven" group were significantly higher （P＜0.05 or P＜0.01）. Compared to those in the "5 seven" group， the FSH， LH and E₂ levels of the "6 seven" group increased， and the AMH and T levels continued to decrease （P＜0.05 or P＜0.01）. Compared to those in the "6 seven" group， the FSH and LH levels of the "7 seven" and older group continued to increase， and the AMH and E₂ levels decreased （P＜0.01）. ConclusionThe law of women reproductive aging in the "seven-year period" theory is basically consistent with the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. The reproductive capacity reaches its peak in the "three-seven-year period" and gradually moves towards reproductive aging in the "four-seven-year period".

Objective:To explore the clinical characteristics of tigecycline-associated hypofibrinogenemia in critically ill patients, and analyze risk factors for its occurrence.Methods:Clinical data of patients treated with tigecycline in the Intensive Care Unit (ICU) at Zhongda Hospital Affiliated to Southeast University from January 2021 to December 2022 were collected and retrospectively analyzed. Patients were divided into hypofibrinogenemia group and non-hypofibrinogenemia group according to their fibrinogen levels. General information, laboratory tests results, tigecycline application, combined drugs, and blood concentration of tigecycline were compared between the 2 groups. Variables with P<0.10 in intergroup comparisons were included in a multivariate logistic regression model to analyze the risk factors for tigecycline-associated hypofibrinogenemia, and odds ratios ( OR) and its 95% confidence intervals ( CI) were calculated. Results:A total of 79 patients using tigecycline were collected, including 43 cases with hypofibrinogenemia and 36 cases without hypofibrinogenemia. Univariate analysis showed that the differences in patients with diabetes [41.9%(18/43) vs. 16.7%(6/36)], acute kidney injury [41.9%(18/43) vs. 19.4%(15/36)], and baseline fibrinogen (before tigecycline treatment) ≤4 g/L [37.2%(16/43) vs. 16.7%(6/36)] between the 2 groups were statistically significant (all P<0.05). The related factors ( P<0.10) of the 2 groups, including diabetes, acute renal injury, continuous renal replacement therapy, baseline FIB ≤4 g/L (before using tigecycline), larger total dose of tegacycline and longer treatment duration, were included in the multivariate logistic regression analysis. The results showed that diabetes ( OR=4.851, 95% CI: 1.180-19.494, P=0.029), continuous renal replacement therapy ( OR=8.610, 95% CI: 1.987-37.311, P=0.004), and longer treatment duration ( OR=1.452, 95% CI: 1.018-2.071, P=0.040) were independent risk factors for tigecycline-related hypofibrinogenemia. Conclusion:In critically ill patients, with diabetes, continuous renal replacement therapy, and longer treatment duration of tigecycline may increase the risk of hypofibrinogenemia.

Objective:To explore the clinical characteristics of tigecycline-associated hypofibrinogenemia in critically ill patients, and analyze risk factors for its occurrence.Methods:Clinical data of patients treated with tigecycline in the Intensive Care Unit (ICU) at Zhongda Hospital Affiliated to Southeast University from January 2021 to December 2022 were collected and retrospectively analyzed. Patients were divided into hypofibrinogenemia group and non-hypofibrinogenemia group according to their fibrinogen levels. General information, laboratory tests results, tigecycline application, combined drugs, and blood concentration of tigecycline were compared between the 2 groups. Variables with P<0.10 in intergroup comparisons were included in a multivariate logistic regression model to analyze the risk factors for tigecycline-associated hypofibrinogenemia, and odds ratios ( OR) and its 95% confidence intervals ( CI) were calculated. Results:A total of 79 patients using tigecycline were collected, including 43 cases with hypofibrinogenemia and 36 cases without hypofibrinogenemia. Univariate analysis showed that the differences in patients with diabetes [41.9%(18/43) vs. 16.7%(6/36)], acute kidney injury [41.9%(18/43) vs. 19.4%(15/36)], and baseline fibrinogen (before tigecycline treatment) ≤4 g/L [37.2%(16/43) vs. 16.7%(6/36)] between the 2 groups were statistically significant (all P<0.05). The related factors ( P<0.10) of the 2 groups, including diabetes, acute renal injury, continuous renal replacement therapy, baseline FIB ≤4 g/L (before using tigecycline), larger total dose of tegacycline and longer treatment duration, were included in the multivariate logistic regression analysis. The results showed that diabetes ( OR=4.851, 95% CI: 1.180-19.494, P=0.029), continuous renal replacement therapy ( OR=8.610, 95% CI: 1.987-37.311, P=0.004), and longer treatment duration ( OR=1.452, 95% CI: 1.018-2.071, P=0.040) were independent risk factors for tigecycline-related hypofibrinogenemia. Conclusion:In critically ill patients, with diabetes, continuous renal replacement therapy, and longer treatment duration of tigecycline may increase the risk of hypofibrinogenemia.

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990^th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female ; Humans ; Male ; Burns/surgery* ; Cicatrix ; Eosine Yellowish-(YS) ; Hyaluronic Acid/therapeutic use* ; Hyperplasia ; Ki-67 Antigen ; Prospective Studies ; Umbilical Cord ; Vimentin ; Young Adult ; Adult ; Middle Aged

Objective:To explore cough cases recorded in ancient traditional Chinese medicine (TCM) books based on the Rules of Latent Structure Differentiation. Method:The 9 323 cough cases in the database of ancient TCM books and pulmonary diseases were extracted. At first, Lantern 5.0 software was used to construct the top 120 TCM hidden structure model with the frequency>100. Then, the obtained hidden variables were comprehensively clustered and interpreted. Result:The 46 hidden variables and 114 hidden classes were obtained through the modeling of 120 traditional Chinese medicines. According to the bayesian information measure (BIC) score, the model score was -161 242.92. The model diagram was formed with Y0, Y5, Y7, Y13, Y35 and Y38 as the cores, and Y36, Y38, Y24, Y19 and Y17 involved 4 hidden classes. Ten comprehensive clustering models were summarized according to the hidden structure flow chart, among which the highest score of Z5 external cold and internal decoction syndrome was 8.4, indicating that the result of syndrome differentiation rules of Z5 had a high degree of support, and the highest mutual information degree and information coverage of Pinellia sinensis were 0.31 and 63%. Z2 had a low score for the syndrome of deficiency of lung qi and Yin, which was -2， and Schisandra had the lowest score of -15, indicating that the syndrome differentiation rules of Z2 was less supportive. Forsythia and Notopterygium both had the highest score of Z6 wind-heat attack lung syndrome and Z10 phlegm and blood-stasis pulmonary syndrome, which was 19.1, indicating that these two TCMs had a great contribution to it. According to the test, the common syndromes of cough were cold and dryness attacking the lung, kidney-Yin deficiency, kidney-Yin deficiency of the lung, cold and internal decoction, wind heat invading the lung, liver fire invading the lung, lung heat burning, phlegm-dampness blocking the lung, phlegm-stasis blocking the lung. The newly discovered cough syndromes were external cold and internal rheum syndrome and phlegm-stasis blocking the lung syndrome. Conclusion:Based on the syndrome differentiation rules of hidden structure, the improved classification of cough syndromes provides ideas for the demonstration of tacit knowledge of TCM and methodological reference for the improvement of syndromes of other diseases, and is conducive to the development of valuable new prescriptions.