1.Exploration of the antidepressant machanism of Shugan hewei tang based on metabolomics of PFC-NAc-VTA neural circuit
Xinyue QU ; Junjie HU ; Juan LI ; Min ZHANG ; Xian ZHOU ; Songlin LIU ; Xin CHEN
China Pharmacy 2025;36(10):1172-1178
OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang (SGHWT) based on the metabolomics of prefrontal cortex (PFC)-nucleus accumbens (NAc)-ventral tegmental area (VTA) neural circuit. METHODS Male SD rats were randomly divided into blank group, model group, SGHWT low-, medium- and high-dose groups [3.67, 7.34, 14.68 g/(kg·d), by raw material], and fluoxetine group [1.58 mg/(kg·d), positive control], with 12 rats in each group. Except for the blank group, the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups, and the corresponding drug solution or normal saline was administered via gavage during modeling, once a day, for 6 consecutive weeks. After the last administration, the body weight, sucrose preference rate, total moving distance, frequency into the center and immobility time of rats in each group were detected. Samples of PFC, NAc and VTA areas of rats in the blank group, model group, SGHWT medium-dose group and fluoxetine positive control groups were collected,and their histomorphological features were observed, and non-targeted metabolomics analysis (except for fluoxetine group)were performed and validated. RESULTS Compared with model group, the cytolysis, structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group, while their body weight, sucrose preference rate, total moving distance and frequency into the center were all significantly higher or longer (P<0.05), and immobility time was significantly shorter (P<0.05). The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified, with 40, 35 and 24 in the PFC, NAc and VTA regions respectively, mainly involved in amino acid, lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, saturated fatty acid biosynthesis, among which alanine, aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 (NMDAR1) in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats, the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.
2.Efficacy and Mechanism of Action of Ermiao Situ Decoction in Modulating JAK/STAT Pathway in Rats with Damp-heat Eczema
Kangning HAN ; Junjie HU ; Juan LI ; Min ZHANG ; Xian ZHOU ; Songlin LIU ; Xin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):37-47
ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene (DNCB), and it was randomly divided into the normal group, the model group, the medium- and high-dose groups of Ermiao Situ decoction (3.40 g·kg-1 and 6.80 g·kg-1), and the prednisone acetate group (2.51 mg·kg-1), with eight rats in each group, totalling 46 rats, of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS, combined with network pharmacology for the prediction of key components, core targets, and signaling pathways, and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin (GAS), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6), Janus kinase 1 (JAK1), phosphorylated (p)-JAK1, signal transduction and activation of transcription factor 3 (STAT3), and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats, which were predicted to act on 198 targets for the treatment of damp-heat eczema, among which the key ingredients included rhodopsin, huangpai alkaloids, and quercetin, and the main core targets included STAT3, tumor necrosis factor (TNF), and IL-6, which were mainly involved in the cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase (Akt) signaling pathway, T helper 17 (Th17) cell differentiation signaling pathway, and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6, JAK1, and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group, rats in the model group were depressed. They had loose hair, loose stools, epidermal oozing, vesiculation, and generation of thick scabs in the form of scales, decreased body weight, increased anus temperature and water intake, and increased indexes of the spleen, thymus gland, and stomach (P<0.05, P<0.01), and the lesion tissue could be seen to be hyperkeratotic, with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned, deficient, and structurally disorganized, and obvious inflammatory cell aggregation was seen. The levels of GAS, IL-4, and IL-13 in serum were significantly reduced (P<0.05, P<0.01), and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the lesion tissue were significantly increased (P<0.05, P<0.01). Compared with those in the model group, rats in each administration group had stable mental states, formed feces, a clean perianal area, and basically normal epidermis. Only a small amount of scaly scabs existed, and the rats had body weight increased, with decreased anal temperature and water intake, as well as decreased spleen, thymus, and gastric indexes (P<0.05, P<0.01). Epidermal thickness was decreased, and epidermal and dermal separation boundaries were obvious, but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased, and the structure was restored to varying degrees. The levels of GAS, IL-4, and IL-13 content in the serum of rats were increased to varying degrees, and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the dermal lesion tissue were significantly decreased (P<0.05, P<0.01). ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.
3.Research progress in antibody drug therapy for relapsed/refractory diffuse large B-cell lymphoma
Yanyan SUN ; Weichen ZHAO ; Chunyuan HE ; Yimiao XIA ; Wei ZHOU ; Yuanyuan ZHEN ; Junjie JIANG ; Facai WANG
China Pharmacy 2025;36(13):1677-1682
Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease. Although standard first-line regimens can cure >50% of patients, approximately one-third of them develop relapsed/refractory DLBCL (r/r DLBCL). Consequently, immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment, antibody-based therapies have evolved rapidly, progressing from monoclonal antibodies (e.g., rituximab, tafasitamab) to bispecific antibodies(e.g., odronextamab,glofitamab, epcoritamab) and antibody-drug conjugate (e.g., polatuzumab vedotin, loncastuximab tesirine). These engineered agents enhance immune cytotoxicity and tumor-specific targeting, providing novel therapeutic options for r/r DLBCL patients.
4.Clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder
Shuping ZHOU ; Shimin LI ; Yingguang SHI ; Liwu ZHENG ; Chaonan CHANG ; Junjie CHEN ; Huanpeng WANG ; Ke SUN ; Xiuhuan WANG ; Linbo LIU
Chinese Journal of Burns 2024;40(7):665-672
Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.
5.Diagnosis and treatment of low anterior resection syndrome after intersphincteric resection for low rectal cancer
Wenhao CHEN ; Junjie ZHOU ; Heng HU ; Xianghai REN ; Xiaoyu XIE ; Qun QIAN ; Congqing JIANG
Chinese Journal of Digestive Surgery 2024;23(6):806-811
Intersphincteric resection (ISR) is an advanced sphincter-preserving surgery for low rectal cancer. Accumulating evidences from clinical studies indicate that ISR can spare some pati-ents with low rectal cancer from the distress of anal amputation while ensuring oncological efficacy. However, due to the necessity of removing part or all of the internal sphincter during rectal resection and the extremely low anastomosis level, a subset of patients may experience low anterior resection syndrome (LARS) after surgery. LARS is characterized by symptoms such as anal incontinence, increased bowel frequency, urgency, incomplete evacuation, and obstructed defecation. Based on relevant literature and team practice, the authors provide an overview of the diagnosis and treat-ment progress of LARS following ISR.
6.The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia
Shiyu DENG ; Jiawang OU ; Zicong HUANG ; Junjie CHEN ; Zihong CAI ; Qifa LIU ; Hongsheng ZHOU
Chinese Journal of Hematology 2024;45(3):257-263
Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.
7.Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells
Huang SHAOWEI ; Xie XUEQIAN ; Xu BO ; Pan ZENGFENG ; Liang JUNJIE ; Zhang MEILING ; Pan SIMIN ; Wang XIAOJING ; Zhao MENG ; Wang QING ; Chen JINYAN ; Li YANYANG ; Zhou LIAN ; Luo XIA
Journal of Pharmaceutical Analysis 2024;14(6):889-901
Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2% DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.
8.The nursing care of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool
Zhixin WANG ; Cong LI ; Junjie ZHANG ; Yongping MA ; Wenhua ZHOU
Chinese Journal of Practical Nursing 2024;40(31):2461-2466
To summarize the nursing experience of a patient with large skin ulcers caused by EBV positive T/NK-cell lymphoproliferative diseases based on TIME Clinical-Decision-Support-Tool. The main points of nursing care were as follows: early identification of the cause of ulceration and active treatment of the underlying disease; accurate and continuous assessment of patients and their wounds; multidisciplinary consultation to ensure the integrity and comprehensiveness of diagnosis and treatment; active identification of obstacle factors and risk control; providing different dressing change programs according to different wound healing stages; evaluation of treatment effects at any time; timely pain management; improving the nutritional status of patients; providing health education and psychological nursing care. After 367 days of wound dressing, the patient′s wound was fully healed, and EBV-DNA was not detected in genetic examination after hematopoietic stem cell transplantation.
9.Chinese expert consensus on targeted and immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer
Ping JIANG ; Zi LIU ; Lichun WEI ; Yunyan ZHANG ; Fengju ZHAO ; Xiangkun YUAN ; Yipeng SONG ; Jing BAI ; Xiaofan LI ; Baosheng SUN ; Lijuan ZOU ; Sha LI ; Yuhua GAO ; Yanhong ZHUO ; Song GAO ; Qin XU ; Xiaohong ZHOU ; Hong ZHU ; Junjie WANG
Chinese Journal of Radiation Oncology 2024;33(10):893-901
Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.
10.A meta-analysis of the effect of post-activation potentiation on athletic performance after activation of lower-extremity relative strength levels
Junjie ZHANG ; Wei ZHOU ; Haiyuan LIU ; Chenggen GUO
Chinese Journal of Tissue Engineering Research 2024;28(28):4586-4592
OBJECTIVE:The effect of post-activation potentiation on sports performance is characterized by increased muscle mobility and increased rate of muscle force generation.In this paper,Meta-analysis is used to quantitatively evaluate the effects of post-activation potentiation on sprint speed,jumping performance,and kinetic parameters(peak impulse,peak power,maximum ground reaction force,rate of force generation,etc.)after activation of relative strength levels in the lower limbs. METHODS:Electronic databases such as CNKI,WanFang,Web of Science,PubMed,and Medline were retrieved for randomized control,random crossover,or clear grouping according to the relative strength levels of the lower limbs(non-randomized controls)on the post-activation potentiation effect after activation induced by the relative strength level of the lower limbs.Free weight equipment and rapid telescopic compound exercises were used as main intervention methods in each group.The publication time of the literature was from the inception of each database until August 5,2023.Endnote software was used to manage the literature.Literature quality assessment was conducted using the PEDro scale for randomized controlled trials and ROBINS-I 2.0 standards for non-randomized controlled trials.Revman5.4 and Stata15.0 software were used to conduct publication bias evaluation,subgroup analysis and sensitivity analysis of the extracted data,and forest plots were produced for Meta-analysis. RESULTS:Eleven documents(seven randomized controlled trials and four non-randomized controlled trials)were finally included,including 216 subjects.Overall,the methodological quality of the literature was high.According to the grouping standard of 1-repetition maximum/body mass>2 for the strong group and 1-repetition maximum/body mass≤2 for the normal group,there were 99 subjects in the strong group and 117 subjects in the normal group,all of whom were male.The positive effect of post-activation potentiation on sprint performance in the strong group was significantly higher than that in the normal group[standardized mean difference(SMD)=-1.34,95%confidence interval(CI):-1.74 to-0.93,P<0.000 01];the positive effect of post-activation potentiation on vertical jump height showed no significant difference between the strong and normal group(SMD=0.30,95%CI:-0.07 to 0.66,P=0.11);the positive effect of post-activation potentiation showed no significant difference between the strong and normal groups in terms of peak impulse(SMD=-0.07,95%CI:-0.62 to 0.47,P=0.61],peak power(SMD=0.21,95%CI:-0.29 to 0.72,P=0.12),maximum ground reaction force(SMD=0.31,95%CI:-0.20 to 0.81,P=0.16)and force generation rate(SMD=0.36,95%CI:-0.11 to 0.82,P=0.39). CONCLUSION:The post-activation potentiation effect in the strong group can significantly increase the short-distance sprint speed.The potentiation effect after activation of the relative strength level of the lower limbs has similar effects on the kinematic and kinetic parameters,including explosive vertical jump height,peak impulse,peak power,maximum ground reaction force and force generation rate.

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