OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

The Menghe Medical School is a highly influential academic school of Chinese medicine in China.Its academic features are mainly learning from others'strengths,openness and tolerance;integrity as the foundation,communication as the strength;harmo-ny as the way,and agility as the technique.The Menghe Medical School originated in Menghe,developed in Shanghai,spread all over the country,and spread around the world.The reasons for the prosperity and development of the Menghe Medical School are analyzed.Among them,imperial doctors being rewarded and supported,the stars having their roots in Menghe,inheritance from teach-ers by blood,help from in-laws,and the establishment of education and leadership in development are the main factors.On the basis of inheriting the scholarship of Menghe Medical School,Professor Tong Xiaolin innovatively proposed academic ideas such as the train-ing path of Xiang thinking,state-target differentiation and treatment,and dosage and effectiveness of prescriptions and medicines,pushing the academic thought of Menghe Medical School to a new theoretical peak in the new era.Based on the majestic development path of the Menghe Medical School,the implications for the inheritance,innovation and development of modern Chinese medicine are analyzed.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*

Objective:To compare closed reduction and intramedullary nailing versus open reduction and locking plate fixation in the treatment of middle and upper humeral fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 62 patients with middle and upper humeral fracture who had been treated at Department of Orthopaedics, The First People's Hospital of Jinmen and at Department of Orthopedics, General Hospital of PLA Central Theater from October 2017 to February 2021. There were 35 males and 27 females, aged from 27 to 86 years. The left side was affected in 24 cases and the right side in 38 cases. All fractures were fresh. According to the AO classification, 16 cases were type A, 32 type B, and 14 type C. Of the patients, 29 were treated with closed reduction and intramedullary nailing (intramedullary nail group) and 33 with open reduction and locking plate fixation (locking plate group). The length of incision, operation time, intraoperative blood loss, hospital stay, fracture healing and complications were recorded and compared between the 2 groups. The pain degree was evaluated by visual analogue scale (VAS) at one week and one month after operation, and the functional recovery of the shoulder was evaluated by Constant-Murley score at one month and 12 months after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The intramedullary nail group was followed up for 12 to 29 months and the locking plate group for 15 to 50 months. In the intramedullary nail group, the length of incision [(4.1±0.7) cm], operation time [(58.3±7.7) min], intraoperative blood loss [(52.7±6.5) mL], and hospital stay [(7.3±1.5) d] were significantly less than those in the locking plate group [(21.7±2.3) cm, (95.8±11.7) min, (237.4±14.9) ml, and (12.3±1.7) d] ( P<0.05). The fracture healing time in the intramedullary nail group was (5.0±1.9) months, significantly longer than that in the locking plate group [(3.5±1.7) months] ( P<0.05). The VAS scores at one week and one month after operation in the intramedullary nail group [(2.8±0.3) points and (1.2±0.5) points] were significantly lower than those in the locking plate group [(4.3±0.4) points and (1.6±0.5) points], and the Constant-Murley score at one month after operation in the intramedullary nail group [(63.5±7.4) points] was significantly higher than that in the locking plate group [(54.3±6.9) points] ( P<0.05). However, at 12 months after operation, there was no significant difference in the Constant-Murley score between the 2 groups ( P>0.05). In both groups, the VAS score at one month after operation was significantly lower than that at one week after operation while the Constant-Murley score at 12 months after operation was significantly higher than that at one week after operation ( P<0.05). In the intramedullary nail group, intraoperative distal refracture happened in one case; in the locking plate group, incision infection occurred in one case and postoperative radial nerve injury in another. There was no significant difference in the incidence of complications between the 2 groups [3.4% (1/29) versus 6.1% (2/33)] ( P>0.05). Conclusion:In the treatment of middle and upper humeral fractures, compared with open reduction and locking plate fixation, closed reduction and intramedullary nailing shows advantages of a smaller surgical incision, shorter operation time, less intraoperative blood loss, shorter hospital stay and faster functional recovery.

Objective:To analyze the correlation between 1H-MRS in hippocampus and peripheral blood cytokines and T lymphocyte subsets in patients with temporal lobe epilepsy, and to explore the relationship between immune dysfunction and the degree of neuronal injury. Methods:Fifty patients with temporal lobe epilepsy were selected from Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021.Clinical data of all patients were collected and they were divided into two groups according to MRI results of epileptic sequence: abnormal hippocampal MRI group ( n=20) and normal hippocampal MRI group ( n=30). Bilateral 1H-MRS scanning of hippocampal and detection of T lymphocyte subsets and cytokines in peripheral blood during interictal period were performed in both groups. The levels of hippocampal metabolites NAA, NAA/(Cr+ Cho), T lymphocyte subsets and cytokines in peripheral blood of the two groups were compared.At the same time, the levels of NAA and NAA/ (Cr+ Cho) in the hippocampus on the abnormal side and the normal side in the abnormal hippocampal MRI group were compared within the group. Finally, the correlation between the levels of metabolites NAA, NAA/ (Cr+ Cho) in the hippocampus on the abnormal side obtained by 1H-MRS scanning and T lymphocyte subsets and cytokines in the abnormal group of MRI was analyzed. The data were statistically analyzed by SPSS 26.0 software. Independent sample t-test or Mann-Whitney U test was used for comparison between the two groups. Paired sample t-test was used for intra group comparison of different sides. Spearman correlation analysis was used to analyze the correlation between each index. Results:The NAA and NAA/(Cr+ Cho) values of the abnormal MRI group(normal side NAA: (1.22±0.37), NAA/(Cr+ Cho): (0.56±0.15). abnormal side NAA: (1.02±0.34), NAA/(Cr+ Cho): (0.48±0.13)) were significantly lower than those of the normal MRI group (NAA: (1.51±0.36), NAA/(Cr+ Cho): (0.73±0.19))(NAA: t=2.705, 4.800, both P<0 05; NAA/(Cr+ Cho): t=3.394, 4.914, both P<0 05). The values of NAA and NAA/(Cr+ Cho) in the abnormal side in the MRI abnormal group were significantly lower than those in the normal side( t=6.467, P<0 05). The levels of IL-1β(11.19(3.56, 20.98)pg/ml), IL-5 (3.12(1.86, 6.41)pg/ml), TNF-α(2.55(1.19, 8.28)pg/ml), CD4+ T lymphocytes((43.13±6.82)%) and Th/Ts((1.96±0.66)) in the hippocampal MRI abnormal group were significantly higher than those in normal MRI group (IL-1β: 3.27(1.63, 6.17)pg/ml, IL-5: 1.15(0.96, 2.96)pg/ml, TNF-α: 1.34(1.02, 2.36)pg/ml, CD4+ T: (38.01±7.21)%, Th/Ts: (1.48±0.53))( Z=-3.041, -2.516, -2.496, all P<0.05; t=2.511, 2.810, both P<0 05). The level of CD8+ T ((23.48±5.33)%) in peripheral blood of abnormal MRI group was significantly lower than that of normal group CD8+ T((27.18±6.08)%)( t=2.210, P<0.05). In the abnormal MRI group, the levels of NAA and NAA/ (Cr+ Cho) in the abnormal hippocampus were negatively correlated with the levels of IL-1β, IL-5 and TNF- α ( r=-0.612--0.463, all P<0.05), and positively correlated with CD8+ T lymphocytes ( r=0.537, 0.478, P<0.05). Conclusion:There is neuronal damage and dysfunction in the abnormal hippocampal region of patients with temporal lobe epilepsy with abnormal hippocampal formation, and the degree of neuronal damage is highly correlated with CD8+ T lymphocytes, IL-5, IL-1β and TNF-α in peripheral blood. The imbalance of interictal lymphocyte subsets and chronic inflammatory response may play an important role in the pathogenesis of epilepsy and neuronal injury .

Karyotyping analysis is a classical cytogenetic method for the prenatal diagnosis of fetal chromosomal aberrations. In order to standardize fetal chromosomal karyotyping analysis and adapt to the development of medical genetics technology, the Committee for the Prevention and Control of Birth Defect, Chinese Association of Preventive Medicine has organized the formulation of this guideline. The content has covered general requirements and standards for the analysis of fetal chromosomal karyotypes, analysis of chromosomal mosaicisms, and methods for determining the resolution of G-banding, etc., with the purpose to serve the clinical practice.

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

Objective To discuss the clinical influence and advantages of applying the local flap of finger tip lateral skin to repair the fingertip defective injuries.Methods From August,2013 to December,2015,used the way of local the flap of finger tip lateral skin to repair the first-fourth fingertip defects for 32 cases and 32 fingers,among which there were 20 males and 12 females;finger categories:11 thumbs,9 index fingers,8 middle fingers and 4 ring fingers.The defective area of fingertips was 0.5 cm×0.8 cm-1.0 cm×1.5 cm,all with bone exposure,23 cases had defects at the end part of phalanx,32 cases had different extent of nail bed defects.Reasons for the injuries:13 cases of grind injuries,11 cases of punch pressing injuries,8 cases of sharp tool cutting injuries.The time from injury to the treatment was 0.5-3.0 h,all of them had no associated injuries.Results Thirty-two cases of finger flaps all survived,with the follow-up for 3-24 months and average follow-up of 6 months,the flaps were slightly bloated after 3 months comparing with the normal skin,there was no contracture in the flap area and pedicle scars,two-point discrimination was 4-5mm,the farinterphalangeal joint flexion was normal.Conclusion The local flap of fingertip lateral skin can repair the defects of fingertip with less scar,not bloated flap,satisfying appearance,operation is simple,and good function,so it's the ideal way to repair the defects of fingertip.

Objective To evaluate the effect of tea polyphenol epigallocatechin gallate (EGCG)on ultraviolet B (UVB)-induced skin pigmentation,transfer and degradation of melanosomes in mice,and to explore the role of autophagy in the mechanism of melanosome degradation.Methods A total of 32 ears from 16 female C57/BL6 mice were randomly and equally divided into 4 groups:acetone control group topically treated with acetone solution daily,EGCG group topically treated with 10 g/L EGCG acetone solution daily,UVB irradiation group irradiated with 500 mJ/cm2 UVB once a day and 2 hours later topically treated with acetone solution,UVB + EGCG group irradiated with 500 mJ/cm2 UVB once a day and 2 hours later topically treated with EGCG acetone solution.Ten days later,all the mice were sacrificed,and skin tissue samples were collected from the ears.Transmission electron microscopy was performed to observe ultrastructural changes of melanosomes and autophagosomes,immunohistochemical study to measure expression of protease-activated receptor 2 (PAR2) and microtubule-associated protein light chain 3 (LC3) in the epidermis,and Western blot analysis to determine the protein expression of PAR2,Rasrelated protein Rab27a and LC3 in the epidermis.Results There was a significant difference in the number of melanosomes and autophagosomes among the acetone control group,EGCG group,UVB irradiation group and UVB + EGCG group (H =12.249,13.888,respectively,both P ＜ 0.05).Compared with the acetone control group,the UVB irradiation group showed significantly increased number of melanosomes (1.85 ± 0.32 vs.1.00 ± 0.41,P ＜ 0.05)and autophagosomes (1.94 ± 0.64 vs.1.00 ± 0.46,P ＜ 0.05) in epidermal keratinocytes in mouse skin.Compared with the UVB irradiation group,the UVB + EGCG group showed significantly decreased number of melanosomes (1.30 ± 0.44,P ＜ 0.05),but significantly increased number of autophagosomes (3.03 ± 0.75,P ＜ 0.05).Immunohistochemical study showed a significant difference in the level of PAR2 in the epidermis among the 4 groups (H =18.700,P ＜ 0.05),and the expression of PAR2 was significantly lower in the UVB + EGCG group than in the UVB irradiation group (7.94 ± 4.57 vs.12.54 ± 3.07,Z =2.143,P ＜ 0.05).However,the 4 groups all showed a low level of LC3,and there was no significant difference among the 4 groups (H =5.051,P ＞ 0.05).Western blot analysis revealed significant differences in the protein expression of PAR2 and Rab27a,as well as in the LC3-Ⅱ/LC3-Ⅰ ratio,among the 4 groups (F =18.739,25.967,24.022,respectively,all P ＜ 0.05).Compared with the UVB irradiation group,the UVB + EGCG group showed significantly decreased expression of PAR2 (0.91 ± 0.54 vs.3.12 ± 0.61,P ＜ 0.05) and Rab27a (0.99 ± 0.16 vs.1.42 ± 0.07,P ＜ 0.05),but significantly increased LC3-Ⅱ/LC3-Ⅰ ratio (1.67 ± 0.08 vs.1.24 ± 0.07,P ＜ 0.05).Conclusion Topical EGCG treatment can effectively suppress UVB-induced skin pigmentation,which may be related to the inhibition of melanosome transfer and promotion of melanosome autophagy.

Background and objectiveComputed tomography-guided needle biopsy (CTNB) is a well-established and commonly used technique for diagnosing pulmonary nodules with high accuracy and safety. Needle-tract implantation after CTNB has been reported in various reports. The aim of this study is to evaluate whether preoperative CTNB affected the distant metastasis and overall survival in pathological stage I-II lung cancer patients.Methods A total of 1,234 patients with pathological stage I-II non-small cell lung cancer were collected. 113 patients received preoperative CTNB, and 1,121 patients did not receive any biopsy before surgical resection. Propensity score-matching method was adopted to balance observed co-variates between two groups, 113 pairs were matched.Cox regression analysis andKaplan-Meier estimates were used to process survival analysis.Results Distant metastasis free survival (DMFS) was significantly poorer in the preoperative CTNB group than in the non-biopsy group (P=0.032). But there was no difference in the overall survival between the two groups (P=0.086). Conclusion CTNB increased the risk of distant metastasis, not increasing the risk of mortality.