1.The Preventive and Therapeutic Approach to Membranous Nephropathy Based on the Theory of "Prevention of Disease Before It Occurs"
Chenyuan NIU ; Guangzhen LIU ; Weiwei SUN
Journal of Traditional Chinese Medicine 2025;66(5):468-472
Based on the theory of "prevention of disease before it occurs", this paper explores the pathogenesis and progression of membranous nephropathy, focusing on the role of "dampness, heat, and blood stasis" as the fundamental causes. The approach emphasizes early prevention, controlling potential risks and secondary factors for disease occurrence. Starting with reinforcing lung defense, preventing blood stasis, and early detection and intervention, prescriptions such as Yupingfeng Powder (玉屏风散) and Xiaochaihu Decoction (小柴胡汤) are recommended. During disease progression, the significant role of dampness and blood stasis in pathogenesis is highlighted. Treatment strategies focus on eliminating dampness and turbidity, clearing heat and promoting urination, cooling blood and resolving blood stasis, activating blood circulation and unblocking meridians, and detoxifying the bowels. Prescriptions like Bixie Fenqing Decoction (萆薢分清饮), Sanren Decoction (三仁汤), and Taohong Siwu Decoction (桃红四物汤) are used. Concurrently, attention should be given to managing complications such as anemia, cardiovascular diseases, and osteoporosis, controlling their progression, and promoting recovery. The approach also includes improving the patient's constitution, regulating emotions, adjusting diet, and preventing colds to reduce recurrence, providing a reference for the prevention and treatment of membranous nephropathy using traditional Chinese medicine.
2.Clinicopathological features of intravascular large B-cell lymphoma and collision tumors of five cases
Jia LIU ; Guangzhen LIU ; Lei XIA ; Hongyan WANG ; Xiaofang ZHANG ; Hui LIU
Chinese Journal of Pathology 2024;53(1):22-28
Objective:To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors.Methods:Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed.Results:There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months.Conclusions:IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.
3.Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells
Yiwei SU ; Guangzhen LI ; Wenxin FANG ; Jinwei ZHANG ; Yimin LIU ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(6):401-407
Objective:To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) .Methods:In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 μmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 μmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 μmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 μmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 μmol/L PQ), and inhibitor group (200 μmol/L PQ+20 μmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted.Results:The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance ( P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group ( P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group ( P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group ( P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group ( P<0.05/3) . Conclusion:CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.
4.Efficacy and safety of Chinese patent medicine in the treatment of benign prostatic hyperplasia:a Bayesian network Meta-analysis
Jia MA ; Jianyue XING ; Yupeng ZHANG ; Guangzhen LIU
Chinese Journal of Pharmacoepidemiology 2024;33(3):301-318
Objective To compare the efficacy and safety of different Chinese patent medicines in the treatment of benign prostatic hyperplasia(BPH)by Bayesian network Meta-analysis.Methods PubMed,EMbase,Cochrane Library,CNKI,SinoMed,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)of Chinese patent medicine in the treatment of BPH from inception to January 1,2023.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Bayesian network Meta-analysis was performed using Stata 15.0 and GeMTC 14.3 software.Results A total of 51 RCTs involving 12 kinds of Chinese patent medicines and 4 927 patients were included.The results of direct Meta-analysis showed that Chinese patent medicine combined with conventional western medicine was superior to conventional western medicine alone in reducing international prostate symptom score(MD=-4.44,95%CI-5.09 to-3.79,P<0.001),improving maximum urinary flow rate(MD=3.16,95%CI 2.71 to 3.61,P<0.001),reducing residual urine volume(MD=-8.27,95%CI-9.62 to-6.92,P<0.001)and prostate volume(MD=-3.89,95%CI-4.60 to-3.18,P<0.001).The results of the network Meta-analysis showed that the Longbishu capsules combined with conventional western medicine had the best effect in reducing the international prostate symptom score.In terms of improving maximum urinary flow rate,Xialiqi capsules combined with conventional western medicine had the best effect.Zegui Longshuang capsules combined with conventional western medicine had the best effect in reducing residual urine volume.In terms of reducing prostate volume,Relinqing granules combined with conventional western medicine had the best effect.The incidence of adverse reactions in the Chinese patent medicine combined with conventional western medicine group(8.27%)was lower than that in the conventional western medicine group(11.98%).Conclusion The existing evidence shows that compared with conventional western medicine alone,Chinese patent medicine combined with conventional western medicine is better than conventional western medicine alone in improving various clinical symptoms of BPH,and has better safety.Various proprietary Chinese patent medicines have different therapeutic focuses,and individualized medication can be used according to the specific symptoms of BPH patients in clinical treatment.Limited by the quantity and quality of the included studies,the above conclusions need to be verified by more high-quality studies.
5.Role of CTGF and PI3K/Akt signaling pathway in paraquat-induced mesenchymal changes in alveolar epithelial cells
Yiwei SU ; Guangzhen LI ; Wenxin FANG ; Jinwei ZHANG ; Yimin LIU ; Zhi WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(6):401-407
Objective:To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) .Methods:In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 μmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 μmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 μmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 μmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 μmol/L PQ), and inhibitor group (200 μmol/L PQ+20 μmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted.Results:The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance ( P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group ( P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group ( P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group ( P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group ( P<0.05/3) . Conclusion:CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.
6.Diagnosis and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement
Dan LUO ; Chenxi XIANG ; Dongshen MA ; Guangzhen LIU ; Meiting FAN ; Yubo WANG ; Jing ZHAO ; Yuqing YUAN ; Qingqing SHEN ; Xinyu LIU ; Hui LIU
Chinese Journal of Pathology 2024;53(6):563-569
Objective:To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis.Methods:The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted.Results:Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months.Conclusions:Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.
7.Research progress on treatment of IgA nephropathy with Traditional Chinese Medicine therapeutic systems
International Journal of Traditional Chinese Medicine 2022;44(3):352-355
The clinical treatment of IgA nephropathy in Traditional Chinese Medicine (TCM) can be treated from theories of Sanjiao, pharynx and kidney, collateral disease and Shaoyang. The Sanjiao theory declaims to clear away damp heat through the whole process of treatment, the upper Jiao lightening the Qi, the middle Jiao clearing away damp heat, and the lower Jiao collecting astringency, strengthening the kidney and cooling blood. The theory of pharynx and kidney focuses on clearing away heat, detoxifying and making benefit of the pharynx, supplemented by tonifying the kidney and strengthening the spleen. In the treatment of collateral diseases, it is considered that the disease is caused by the external invasion of disease pathogens or the damage of the vein caused by the influence of evil Qi. The treatment should be combined with strengthening the right and eliminating evil, and paying attention to promote blood circulation and remove blood stasis. The disease is caused by pooring Qi mechanism of Sanjiao and evil invading Shaoyang. The above TCM systems showed different treatment, but they all improve symptoms, reduce urinary protein quantification, improve quality of life with less adverse events.
8.ALK-positive large B-cell lymphoma with EBV infection or cyclin D1 expression: a clinicopathological analysis of 3 cases
Wanna WU ; Chenxi XIANG ; Dongshen MA ; Guangzhen LIU ; Hui LIU
Chinese Journal of Pathology 2022;51(6):506-511
Objective:To investigate the clinicopathological features and misdiagnosis factors of ALK positive large B-cell lymphoma (ALK +LBCL). Methods:The clinicopathological data of 3 patients with ALK +LBCL in the Department of Pathology, the Affiliated Hospital of Xuzhou Medical University from 2010 to 2021 were collected retrospectively. Immunohistochemistry (IHC) was used for immunophenotyping, in-situ hybridization (ISH) for EBV-encoded RNA (EBER) detection, in-situ fluorescence hybridization (FISH, break-apart probes) for ALK, MYC, and CCND1 translocations. Next-generation sequencing (NGS) was used for the detection of gene fusions and mutations. And clinicopathological features and prognosis of patients were analyzed. Results:Among the 3 ALK +LBCL patients, there were 2 males and 1 female, aged 42, 59, and 39 years, respectively, none of which presented with B symptoms. Case 1 showed systemic lymphadenopathy with elevated serum EBV DNA loading, while cases 2 and 3 presented with extranodal lesions in the nasal and hard palate, respectively. Bone marrow biopsies were performed in cases 1 and 3, and neither showed involvement. Case 1 was at clinical stage Ⅲ while both cases 2 and 3 were at stage Ⅰ, and IPI score ranged 0-1 in all cases. The morphology of these cases was similar. The architecture was effaced by sheets of cohesive large cells growing in extensive infiltration and intra-sinus growth pattern. The neoplastic cells showed immunoblastic or plasmablastic morphology, and large anaplastic cells were easily found. The tumor cells expressed ALK protein cytoplasmically in almost all cells, with ALK gene translocations detected by FISH. Common B-cell and T-cell markers, including CD20, PAX5, CD19, CD2, CD3, CD5, CD7, CD43, CD56, and bcl-2, were negative, while plasmacytic differentiation markers, including CD138, CD38, and MUM1, were positive; CD22, BOB1 and OCT2 were variably expressed. CD10 was strongly expressed only in case 3. All cases were negative for bcl-6 but positive for CD4, perforin, CD30 (partial cells), pSTAT3 (diffusely), and MYC (40%-50%). The Ki-67 index was ranged 60%-70%. MYC translocation was not detected in any case by FISH. In case 1, EBER was strongly positive in>90% of tumor cells. Case 3 was diffusely positive for cyclin D1 but negative for SOX11 expression and CCND1 translocation. All cases harbored ALK fusion genes detected by NGS. In case 1, the fusion partner was TFG, which had not been reported in DLBCL, while in the other 2 cases, ALK fused with the CTCL gene, which was commonly seen in ALK +LBCL. Cases 1 and 3 were treated with ECHOP-based chemotherapy for six cycles and were followed up for 70 and 27 months, respectively, and both achieved complete remission. Conclusions:ALK +LBCL cases with diffuse EBER-positivity reported in this study show TGF as a new fusion partner of ALK in DLBCL, together with cyclin D1 expression. These rare cases are easily confused with EBV positive diffuse large B-cell lymphoma, not otherwise specified (EBV +DLBCL, NOS), cyclin D1 positive diffuse large B-cell lymphoma (cyclin D1 +DLBCL) and ALK positive anaplastic large cell lymphoma (ALK +ALCL), resulting in misdiagnosis. Being aware of these rare phenotypes is essential for pathologists to diagnose ALK+LBCL and guide appropriate treatment accurately.
9.Clinicopathological features of mixed cervical carcinoma with adenoid cystic pattern
Linlin LI ; Yingying CUI ; Pengying GAO ; Lei XIA ; Guangzhen LIU ; Hui LIU
Chinese Journal of Pathology 2022;51(7):615-620
Objective:To investigate the clinicopathological characteristics, immunophenotype, molecular characteristics, differential diagnosis, clinical treatment and prognosis of mixed carcinoma of cervix with adenoid cystic pattern.Methods:Three cases of mixed cervical carcinoma with adenoid cystic pattern were collected at the Affiliated Hospital of Xuzhou University Medical School from 2018 to 2021.The clinicopathological characteristics were analyzed, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed. The related literature was reviewed.Results:The three patients were postmenopausal women with a median age of 74.7 years. The clinical symptom was vaginal bleeding without obvious causes. One case was an endophytic tumor, and the others were exophytic. The median diameter of the three cases was 3.3 cm. Two patients underwent hysterectomy, the tumors infiltrated the external 1/3 and middle 1/3 of the cervix respectively. All the lymph nodes were negative. One patient had a previous biopsy. Microscopically, all three tumors were characterized by a cribriform structure, which were filled with basophilic myxoid substance and surrounded by tubules lined by two layers of cells. The tumor cells had scanty cytoplasm and showed the characteristics of cervical basal-like cells. All three cases were accompanied by high-grade squamous intraepithelial lesions and squamous cell carcinoma, and one also showed a non-specific spindle cell sarcomatoid component. Within the double-layered epithelial structure, the outer epithelium was positive for p63, CD117, p16 INK4a (clone E6H4) and MYB protein and negative for S-100 by IHC. The combined positive score of PD-L1 (clone 22C3) was less than 1 in all three cases. Human papillomavirus (HPV) types 16 and 18 were detected in one patient preoperatively, while high-risk HPV were positive in the other two patients by RNAscope ISH postoperatively. None of the three cases showed MYB gene rearrangement by FISH. The mean follow-up time was 23.3 months (36, 28 and 6 months, respectively). Two patients underwent hysterectomy and radiotherapy survived without disease. One patient survived with tumor just by radiotherapy and drug therapy. Conclusions:Mixed cervical carcinoma with adenoid cystic pattern is extremely rare. It is a high-grade malignancy with poor prognosis. The tumor is associated with high-risk HPV infection, without MYB gene rearrangement, and with low PD-L1 immunoreactivity. Radical surgery combined with radiotherapy and chemotherapy is the mainstay of treatment at present.
10.Determination and Evaluation of Antimicrobial Effectiveness of 10% Chloral Hydrate Solution
Guangzhen LIU ; Guojin WANG ; Xiangang LI ; Gang CHEN ; Lin LIN
China Pharmacist 2017;20(2):372-374
Objective:To determine and evaluate the antimicrobial effectiveness of 10% chloral hydrate solution. Methods:The determination of antimicrobial effectiveness of 10% chloral hydrate solution from two different manufacturers was carried out according to Chinese Pharmacopoeia (2015 edition). Results:The antimicrobial effectiveness of 10% chloral hydrate solution met the require-ments of Chinese Pharmacopoeia (2015 edition). Conclusion:10% Chloral hydrate solution shows adequate antimicrobial effective-ness.

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