Immunoglobulin A (IgA) nephropathy is a globally prevalent type of primary glomerulonephritis, characterized by complex symptoms and diverse clinical manifestations. The internationally recognized " multiple hit hypothesis" explains the systemic immune disease features of IgA nephropathy. However, current treatment strategies primarily focus on local pathological changes, inadequately addressing its complex systemic mechanisms. The " qi cycle in round" theory, an integral concept of the academic thought of HUANG Yuanyu, a prominent medical expert from the Qing Dynasty, offers a concise and insightful framework for understanding complex pathologies. For example, this theory provides valuable insights for elucidating the pathogenesis of IgA nephropathy and guiding its clinical management by simplifying intricate systemic processes. This study applies the " qi cycle in round" theory to postulate that patients with IgA nephropathy experience disrupted qi flow owing to spleen-stomach qi deficiency and dampness-heat accumulation. These imbalances manifest as internal symptoms, such as diarrhea; external vulnerability to illness; upper body symptoms, like sore throat; and lower body symptoms, such as hematuria and proteinuria. Pathologically, the condition is characterized by immune complex deposition. This article also emphasizes strategies that prioritize tonifying spleen-stomach qi to enhance the pivotal functions of transportation and transformation. Regulating qi and relieving stagnation are emphasized to harmonize ascending and descending dynamics. Additionally, eliminating turbidity and unblocking collaterals are highlighted to promote qi transformation. These approaches aim to restore the harmonious operation of organ qi dynamics and harmonious qi transformation functions. This study aims to provide a reference for syndrome differentiation and IgA nephropathy treatment using traditional Chinese medicine based on the " qi cycle in round" theory.

Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1⁺ NK cells (t = 8.45, P < 0.05) and DX5⁺ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1⁺ DX5⁺ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1⁺ NK cells (t = 4.58, P < 0.05) and PD-1⁺ DX5⁺ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5⁺ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5⁺ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5⁺ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5⁺ NK cell subsets.

Objective:To investigate the effects of basal luteinizing hormone(bLH)and different luteinizing hor-mone/follicle stimulating hormone ratio(LH/FSH)on the pregnancy outcome of in vitro fertilization or intracyto-plasmic sperm injection(IVF/ICSI)in patients with polycystic ovary syndrome(PCOS).Methods:From July 2013 to January 2020,424 PCOS patients who underwent flexible gonadotropin-releasing hormone antagonist protocol for ovulation induction in first IVF/ICSI were collected retrospectively from the department of reproductive medi-cine,The First Affiliated Hospital of Nanjing Medical University.The patients were divided into normal bLH(LH≤10 U/L,316 cases)and high bLH(LH>10 U/L,108 cases)group according to different levels of bLH;At the same time,according to the different levels of LH/FSH ratio,they were divided into low ratio(LH/FSH≤1,227 cases)group,median ratio(10.05).②Compared with patients in different LH/FSH ratio groups,the high ratio group had higher AMH and antral follicle count(AFC)than the other two groups,and the differences were statistically significant(P<0.05).In terms of ovulation induction,the high ratio group had lower numbers of retrieved eggs,transferred embryos,and endometrial thickness on HCG day compared to the other two groups,with statistically significant differences(P<0.05).There was no statistically significant difference in pregnancy outcome indicators among the three groups of patients(P>0.05).③Binary Logistic regression analy-sis showed no significant correlation between live birth rate and bLH,LH/FSH ratio(P>0.05),but the live birth rate was related to the number of embryos transferred(P<0.05).Conclusions:Elevated bLH level and LH/FSH ratio may affect the outcomes of ovulation induction in women with PCOS(such as the number of oocytes re-trieved and endometrial thickness on HCG injection day),but there is no significant correlation with live birth rate of assisted reproduction.

Diabetic kidney disease(DKD)is a severe complication of diabetes.Its incidence increases annually,posing a significant burden on public health.The strategy of symptomatic treatment based on pathogenesis differentiation,focusing on identifying pathogenesis,is particularly meaningful for managing complex and variable chronic diseases like DKD.Within this framework,the state of latent heat persists throughout DKD,with"latent heat causing accumulation"identified as the core pathogenesis affecting and promoting the development and progression of DKD.This paper is centered on the concept of"latent heat causing accumulation"and adopts symptomatic treatment based on pathogenesis differentiation as its guiding principle to explore the role of latent heat in DKD.It highlights that the onset of DKD involves environmental and constitutional pathogenesis associated with"the concealment of latent heat"and"stagnant-heat invading collaterals"as the initial pathogenesis,"latent heat causing accumulation"as the core mechanism,and"secondary turbid heat"as the derivative pathogenesis.These pathogenesis factors collectively influence the symptoms,sequelae,and prognosis of DKD.Moreover,this paper provides commonly used prescriptions for different stages,syndrome types,and complications of the disease,aiming to offer a reference for clinical practice in flexibly addressing changes in disease conditions based on varied pathogenesis.

Malignant tumors pose a serious threat to human health and are one of the main causes of human death worldwide.In order to further improve the therapeutic outcomes of malignant tumors and prolong patients'survival time,clarifying the pathogenesis of malignant tumors and searching for new diagnostic and therapeutic targets become particularly important.It has been found that the occurrence and development of malignant tumors are the results of the interaction between tumor cells and the tumor microenvironment(TME).Versican,encoded by the VCAN gene,is a type of chondroitin sulfate proteoglycan belonging to the exogenous lectin proteoglycan family.It is a major component of the extracellular matrix and plays an important role in embryonic development and inflammatory responses.As an important component of TME,versican is abnormally expressed in various tumor tissues such as renal cell carcinoma,hepatocellular carcinoma,and gastric cancer,and is closely related to the clinical pathological characteristics and prognosis of the patients.It is a potential biomarker for early diagnosis and prognostic evaluation of tumors.Further researches have shown that versican can promote tumor development in a number of ways,such as promoting tumor cell proliferation,invasion and metastasis,inhibiting tumor cell apoptosis,promoting tumor angiogenesis,and inhibiting anti-tumor immune responses.This article reviews the current research status of the expression and biological effects of versican in malignant tumors,aiming to provide reference for subsequent research,clinical diagnosis and treatment of tumors.

Objective In this study,we aimed to use network pharmacology techniques to predict the key targets of a prescription of Ziziphi spinosae semen formula(ZSSF)compound for depression,and to verify its mechanism of action using a zebrafish model of rifampicin-induced depression.Methods The drug targets of ZSSF were retrieved from the TCMSP database,and the target names were corrected using the UniProt database.Depression-related targets were identified using the GeneCards,OMIM,and NCBI databases.Protein-protein interaction information for the shared targets was predicted using the STRING database.The collected data were then analyzed using the Metascape database to determine GO and KEGG pathway enrichment,and the result were visualized using microbiotics.Behavioral experiments and reverse-transcription quantitative PCR experiments were conducted to verify the therapeutic effects of ZSSF on a zebrafish depression model induced by risperdal.Results 188 targets were screened to find the interactions between depression and ZSSF.The protein-protein interaction result showed that ZSSF primarily targeted TNF-α,IL-2,IL-6,IL-1β,and IL-10 to produce its antidepressant effect.KEGG pathway enrichment analysis revealed that ZSSF exerted its effects on depression through various signaling pathways,including the TNF,PI3K-Akt,and cGMP-PKG signaling pathways.The result of the animal experiments showed that the treatment groups given high,medium,and low doses of ZSSF exhibited significant improvements in movement distance under acoustic and light stimulation compared with the model group(P＜0.05).The speed of movement of the treatment groups was also significantly faster(P＜0.01).Additionally,the mRNA expression levels of TNF-α,IL-2,IL-6,IL-1β,and IL-10 were up-regulated in the brain tissues of zebrafish in the high-,medium-,and low-dosage groups of ZSSF compared those in the model group(P＜0.001).Conclusions ZSSF exerts its antidepressant effect through multiple components and targets,and its antidepressant effects may be associated with its inhibition of inflammatory factors.

Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the pa-rameters in the diagnosis of anxiety and depression in PD patients.Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The gener-alized anxiety scale(GAD-7)and the patient health questionnaire(PHQ-9)were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were col-lected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW)were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients.Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0% ,respectively.There were differences in the dialysis period(Z=-2.358,P =0.018;Z =-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z =-4.587,P<0.001;Z=-7.367,P<0.001)between the anxiety group and the non-anxiety group as well as between the de-pression group and the non-depression group.The correlation analysis showed that MPV(r =0.358,P<0.001;r =0.489,P<0.001)and PDW(r =0.340,P<0.001;r =0.447,P<0.001)were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P =0.022,P =0.011),PDW(P =0.041,P =0.018),and dialysis period(P =0.011,P =0.030)were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively.Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.

Objective To predict the structure and antigenic epitope of the Strongyloides stercoralis serine protease inhibitor 1 (Ss-SRPN-1) protein using bioinformatics tools, and to construct prokaryotic expression plasmids for expression of recombinant Ss-SRPN-1 protein, so as to provide the basis for unraveling the function of the Ss-SRPN-1 protein. Methods The amino acid sequence of the Ss-SRPN-1 protein was downloaded from the NCBI database, and the physicochemical properties, structure and antigenic epitopes of the Ss-SRPN-1 protein were predicted using bioinformatics tools, including ExPASy, SWISS-MODEL and Protean. Primers were designed according to the nucleotide sequences of Ss-SRPN-1, and the Ss-SRPN-1 gene was amplified, cloned and sequenced with genomic DNA extracted from the infective third-stage larvae of S. stercoralis as a template. The Ss-SRPN-1 protein sequence was cloned into the pET28a (+) expression vector and transformed into Escherichia coli BL21 (DE) cells for induction of the recombinant Ss-SRPN-1 protein expression. The recombinant Ss-SRPN-1 protein was then purified and identified using Western blotting and mass spectrometry. Results Bioinformatics analysis showed that the Ss-SRPN-1 protein, which was composed of 372 amino acids and had a molecular formula of C₁₉₄₈H₃₀₄₆N₄₈₈O₅₇₅S₁₆, was a stable hydrophilic protein, and the subcellular localization of the protein was predicted to be extracellular. The Ss-SRPN-1 protein was predicted to contain 11 dominant B-cell antigenic epitopes and 20 T-cell antigenic epitopes. The Ss-SRPN-1 gene with a length of 1 119 bp was successfully amplified, and the recombinant plasmid pET28a (+)/Ss-SRPN-1 was constructed and transformed into E. coli BL21(DE) cells. The expressed recombinant Ss-SRPN-1 protein had a molecular weight of approximately 43 kDa, and was characterized as a Ss-SRPN-1 protein. Conclusions The recombinant Ss-SRPN-1 protein has been expressed successfully, and this recombinant protein may be a potential vaccine candidate against strongyloidiasis.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective:To observe the path and anatomic distribution of cutaneous branch of second dorsal metacarpal artery(SDMA) from the back of hand to the web of the fingers, and to explore the feasibility and clinical effect on the transfer of free flap of SDMA.Methods:Between June 2018 and September 2018, with perfusion of red latex, 22 hand specimens were dissected to explore the course, vessel calibre and distribution of cutaneous branches of SDMA, and to discover the existence of an innervation of cutaneous nerve in Department of Hand Surgery of Tangshan Second Hospital. Later on, from February 2019 to July 2020, 2 thumb pulp defects of 2 patients were reconstructed with the free flaps of SDMA. One defect was in the left thumb and the other in the right, both were male and compression injuries. Size of thumb pulp and a skin defect was at 3.5 cm×2.0 cm in 1 patient, and 2.0 cm×2.5 cm in the other. There was no neurovascular injury, but 1 patient had a distal phalangeal fracture and a nail bed laceration. The sizes of the flaps were 3.8 cm×2.3 cm and 2.8 cm×2.5 cm. Functional exercises started from 3 weeks after surgery. Patients attended postoperation follow up regularly by outpatient visit, telephone or internet interviews. Follow-up observations included the appearance, texture, sensory recovery of the flaps and thumb functions.Results:Multiple perforating branches (4-9 branches) were found from SDMA, which distributed in the distal 1/3 of SDMA in the anatomic study. It was found that the outer diameter of SDMA was 0.76 mm±0.25 mm at the intersection of extensor tendon of index finger and that of the digital web artery was 0.71 mm±0.12 mm. The length of digital web artery was 11.00 mm±1.27 mm. The 2 surgically transferred flaps were all survived. One patient showed the function of thumb in excellent with two-point discrimination (TPD) at 7.0 mm, at 18 months of follow-up. The other patient showed good thumb movement, soft and elastic skin of the flap and with a 7.5 mm in TPD, at 15 months of follow-up. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the results of the 2 flaps were all excellent.Conclusion:The flap of SDMA has a constant cutaneous nerve and a long vascular pedicle with an ideal vessel size. It is suitable for free transfer and can be used to reconstruct soft tissue defects of thumb.