1.Changes of Immunological Indexes and Blood Routine in Treatment of Aplastic Anemia by Yiqi Yangxue Prescription
Yaoyin ZHANG ; Chaochang ZHANG ; Jiaqi HE ; Wenru WANG ; Yubin DING ; Jinhuan WANG ; Ruirong XU ; Haixia DI ; Jiangwei WAN ; Qifeng LIU ; Haixia WANG ; Antao SUN ; Xudong TANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):97-104
ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia (AA) and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters, thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted, involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters [including hemoglobin (HGB), white blood cell count (WBC), platelet (PLT), and absolute neutrophil count (ANC)] after 6 months of treatment. One group had the elevation <50%, and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%, the group with HGB elevation≥50% showed elevated level of CD3+ human leukocyte antigen-DR (HLA-DR)+ and increased proportion of patients with T-helper cell type 2 (Th2)<5%, CD8+≥50%, and CD3+HLA-DR+≥9% before treatment (P<0.05, P<0.01). The multivariate Logistic regression analysis showed that CD8+≥50% before treatment was the independent influencing factor for HGB elevation ≥50% [odds ratio (OR)=12.000, 95% confidence interval (CI) 2.218, 64.928, P<0.01]. ② Compared with the group with WBC elevation<50%, the group with WBC elevation≥50% showed increased proportion of patients with CD3+HLA-DR+<6% and T-box transcription factor (T-bet)≥200% before treatment (P<0.05). The multivariate Logistic regression analysis showed that CD3+HLA-DR+<6% (OR=2.998, 95%CI 1.036, 8.680, P<0.05) and T-bet≥200% (OR=3.634, 95%CI 1.076, 12.273, P<0.05) before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%, the group with PLT elevation≥50% presented lowered Th1 and CD3+HLA-DR+ levels and increased proportion of patients with Th1<12%, CD4+≥6%, and CD3+HLA-DR+<5% before treatment (P<0.05, P<0.01). The multivariate Logistic regression analysis showed that CD3+HLA-DR+<5% before treatment was the independent influencing factor for PLT elevation≥50% (OR=16.190, 95%CI of 3.430 to 76.434, P<0.01). ④ Compared with the group with ANC elevation<50%, the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB, Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3+HLA-DR+≥9%, especially those with CD8+≥50%. As for the AA patients with rapid elevation in WBC, the therapy was particularly effective in the patients with CD3+HLA-DR+<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT, the therapy was particularly effective in the patients with Th1<12% and CD4+≥6%, especially those with CD3+HLA-DR+<5%.
2.Comparing the efficacies of different treatments for T lymphoblastic lymphoma
Andie FU ; Xiaojian ZHU ; Yang YANG ; Lifang HUANG ; Jinhuan XU ; Yang CAO ; Yi XIAO ; Fankai MENG ; Donghua ZHANG ; YiCheng ZHANG
Chinese Journal of Organ Transplantation 2024;45(2):75-81
Objective:To explore the differential efficacies of conventional chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL) .Method:From January 2012 to December 2022, the relevant clinical data were retrospectively reviewed for 82 T-LBL patients hospitalized at Affiliated Tongji Hospital. According to different treatments, they were assigned into two groups of non-transplantation (49 cases) and transplantation (33 cases). The transplantation group was divided further into two groups of allo-HSCT (22 cases) and auto-HSCT (11 cases) according to different transplantation modes. In non-transplantation group, remission was induced mostly by cyclophosphamide+messosodium+doxorubicin+dexamethasone+vincrine/methotrexate+Hyper CAVD A/B. Six patients achieved remission based upon cyclophosphamide+cytarabine+6-mercaptopurine (CAT), etoposide+vincristine+doxorubicin+cyclophosphamide+cyclophosphamide+ prednisone (EPOCH), high-dose methotrexate+dexamethasone and vincristine+pirubicin+ cyclophosphamide+ pemasase+prednisone (VDCLP). The transplantation group underwent HSCT after multi-drug combination intensive induction therapy. Efficacy and survival were analyzed by observing the rates of overall survival (OS) and progression-free survival (PFS) .Result:There were 64 males and 18 females with a median age of 23 (11~74) year. Among them, 62 cases (75.61%) had clinical stage Ⅲ~Ⅳ. And 43 cases (53.44%) had systemic symptoms (B symptom) of fever, night sweats and weight loss at an onset of disease. Fifty cases (61.00%) had an involvement of bone marrow and 33 cases (80.5%) belonged to Ann Arbor stage Ⅲ and above. There were 65 cases (79.27%) with Eastern Cooperative Oncology Group (ECOG) score ≤2 and 17 cases (20.73%) with ECOG score >2. International Prognostic Index (IPI) was ≤3 (63 cases, 76.83%) and >3 (19 cases, 23.17%). Follow-up period was 27.5 (5~118) month. And 3-year OS and PFS were 53.64% (95% CI: 42.35%~64.62%) and 47.56% (95% CI: 36.53%~58.82%). Significant inter-group difference existed in 3-year OS[42.86% (95% CI: 29.12%~57.71%) vs 69.70% (95% CI: 51.13%~83.79%), P=0.014]and 3-year PFS was 38.76% (95% CI: 25.54%~53.76%) and 60.61% (95% CI: 42.24%~76.57%). And the difference was statistically significant ( P=0.032) . Conclusion:As a consolidation therapy, HSCT may improve the long-term outcomes of T-LBL patients as compared with chemotherapy alone.
3.Meta-analysis of clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst
Luliang LIU ; Jinhuan SUN ; Xiaofei WU ; Yuanyuan ZHANG ; Boyu GU ; Fulin GUO
China Modern Doctor 2024;62(31):36-41
Objective Meta-analysis was performed to evaluate the clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst.Methods Randomized controlled trials comparing fenestration decompression and curettage in treatment of jaw cysts were retrieved from PubMed,Cochrane Library,CNKI,SinoMed,VIP and Wanfang data from built databases to June 2024.A Meta-analysis was performed using RevMan 5.4 software to compare the rate of capsule volume reduction,bone hyperplasia thickness and bone density at 3,6 and 12 months after treatment with two methods.Results A total of 14 literatures were included.At 3,6 and 12 months after operation,rate of capsule volume reduction and bone density after fenestration decompression were significantly better than that after curettage.At 6 and 12 months after operation,bone hyperplasia thickness after fenestration decompression were significantly greater than that after curettage.Conclusion Fenestration decompression is superior to curettage in the treatment of jaw cyst in terms of rate of capsule volume reduction,bone hyperplasia thickness and bone density.
4.Research progress in molecular mechanism of acupuncture for diabetes mellitus.
Kaiting HE ; Qinhong ZHANG ; Jinhuan YUE ; Tong PU ; Hao CHI ; Qiaoyun WU ; Songhe JIANG ; Guanhu YANG
Chinese Acupuncture & Moxibustion 2024;44(11):1357-1362
This paper discusses the mechanism of acupuncture for diabetes mellitus from the perspective of molecular biology, aiming to reveal the potential rules of restoring the balance in the body and fighting against diabetes mellitus (DM). By searching the basic research literature of acupuncture treatment for DM, it is found that the molecular biological mechanism of acupuncture treatment for DM is closely related to the regulation of insulin signaling pathway, the modulation of inflammatory response, the protection and regeneration of islet β-cells, fat metabolism and energy balance. It points out that there are few studies of acupuncture on the type 1 diabetes mellitus and the large-scale randomized controlled trials, as well as the studies on the upstream regulation mechanism, the specific cellular molecules and the interaction mechanism of various molecules. It needs to deepen the multi-level, multi-target and multi-dimensional exploration on the molecular biological mechanism of acupuncture for diabetes mellitus.
Humans
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Acupuncture Therapy
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Diabetes Mellitus/genetics*
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Animals
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Insulin/metabolism*
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Signal Transduction
5.Early Efficacy Predictors of Bushen Shengxue Prescription Combined with Western Medicine in Treatment of Aplastic Anemia
Chaochang ZHANG ; Jian LIU ; Wenru WANG ; Rui LI ; Qifeng LIU ; Jinhuan WANG ; Jiangwei WAN ; Ruirong XU ; Feng LIU ; Rou MA ; Xudong TANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):64-72
ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia, and provide prognosis indicators for the treatment of aplastic anemia (AA) with kidney-tonifying therapy in traditional Chinese medicine (TCM) combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment, the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age, sex, disease severity (including severe aplastic anemia and non-severe aplastic anemia), course of disease, degree of bone marrow nucleated cell proliferation, baseline hemogram levels [including white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (HGB), platelets (PLT), and reticulocytes (RET)], T lymphocytes subsets, and the expression levels of T-box transcription factor (T-bet) and GATA-binding protein-3 (GATA-3) were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of [20, 40) and [60, 80) were higher in the 4-month effective group (P<0.05). The sex, disease severity, course of disease, and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB, WBC, ANC, and PLT than the 4-month ineffective group (P<0.05), and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time, while other indicators did not affect the onset time. The receiver operating characteristic (ROC) curve was established to analyze the value of PLT level before treatment for predicting the onset time, and the area under the curve was 0.691. With the critical value of 40.5×109/L, the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893, respectively. The two groups of patients were graded according to age {(14, 20), [20, 40), [40, 60), and [60, 80)} and PLT level before treatment (PLT<40×109/L, PLT≥40×109/L). The proportion of the patients with PLT≥40×109/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group (P<0.05). The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment (P<0.05). The levels of Th1 cells, Th2 cells, CD4+ T cells, and CD8+ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment (P<0.05), while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of [20, 40) or [40, 60), with higher levels of HGB, WBC, ANC, and PLT (especially those with PLT≥40×109/L), lower level of total T lymphocytes, or higher T-bet expression level before treatment.
6.Analysis of Predictive Factors for Efficacy of Yiqi Yangxue Prescription Combined with Western Medicine in Treatment of Aplastic Anemia in Non-elderly Adults
Chaochang ZHANG ; Rui LI ; Jian LIU ; Yubin DING ; Jinhuan WANG ; Qifeng LIU ; Ruirong XU ; Haixia WANG ; Haixia DI ; Antao SUN ; Yonggang XU ; Xiupeng YANG ; Feng LIU ; Rou MA ; Xudong TANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(20):88-98
ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia (AA) in non-elderly adults, so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6th month of treatment, the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender, age, disease classification [non-severe aplastic anemia (NSAA)/severe aplastic anemia (SAA)], course of disease, family history, complications, history of drug allergy, baseline blood routine examination [hemoglobin (HGB), white blood cell (WBC), neutrophil (ANC), platelet (PLT), and reticulocyte (Ret)], T lymphocyte subsets, degree of proliferation of nucleated cells in bone marrow, and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study, including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group (P<0.05). The body height, body weight, gender, age, disease classification, course of disease, family history, and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment (P<0.05) and higher proportion of patients with ANC≥1.6×109/L and PLT≥25×109/L (P<0.05, P<0.01) than the ineffective group. The baseline levels of WBC, HGB, and Ret showed no significant statistical differences between two groups. The levels of CD3+HLA-DR+T cells in the effective group before treatment was higher than that in the ineffective group (P<0.05). The levels of CD3+CD19-T cells, CD4+T cells, CD8+T cells, Th1 cells, Th2 cells, and CD3+CD25+T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group (P<0.05). The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy (P<0.05, P<0.01), while other indicators were not influencing factors for efficacy. The receiver operating characteristic (ROC) curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 (P<0.05), with the critical value of 1.595×109/L, the sensitivity of 0.42, and the specificity of 0.95. ConclusionThe history of drug allergy, pre-treatment ANC, PLT, CD3+HLA-DR+ T cell levels, and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy, higher ANC and PLT levels before treatment, especially those with ANC≥1.6×109/L, PLT≥25×109/L, and higher CD3+ HLA-DR+T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.
7.Professor SUN Weizheng's Experience in Diagnosing and Treating Multiple Myeloma with the Clearing-Releasing Therapy
Dandi HE ; Jinhuan WANG ; Chunyu ZHANG ; Antao SUN ;
Journal of Traditional Chinese Medicine 2023;64(24):2500-2504
The article summarized professor SUN Weizheng's clinical experience in treating multiple myeloma using the clearing-releasing therapy. It is believed that the mechanism of multiple myeloma is kidney essence insufficiency, pathogenic toxin erosion, and blinding of phlegm and stasis. The treatment should consider both the deficiency and the excess, and the root and branch. Thus, the clearing-releasing therapy is proposed. “Clearing” refers to the approach of supplementing deficiency and reinforcing health while advocating the use of clearing and supplementing products to replenish without generating additional pathogenic factors. Additionally, products that clear heat, resolve toxins, dispel stasis, dissolve phlegm, and eliminate masses is suggested to benefit for clearing away pathogenic toxins. “Releasing” means to replenish the normal yang qi with sweet-warm and acrid-warm products on the basis of “clearing” method, and to release the cold pathogen constraint in the muscles and bones. Based on the principle of clearing and releasing, the selfmade Jishi Beverage (济世饮) is formulated to supplement the kidney and secure essence, dispel phlegm and dissolve stasis, resolve toxins and dissipate masses. The prescription can be modified according to syndrome differentiation. It is also advocated to use multiple methods and pay attention to external therapies such as enema for relieving constipation and draining heat, and to combine acupuncture and medicine to relieve pain.
8.A single-cell landscape of triptolide-associated testicular toxicity in mice
Wei ZHANG ; Siyu XIA ; Jinhuan OU ; Min CAO ; Guangqing CHENG ; Zhijie LI ; Jigang WANG ; Chuanbin YANG
Journal of Pharmaceutical Analysis 2023;13(8):880-893
Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.
9.Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels
Wanhe LUO ; Jinhuan LIU ; Shanling ZHANG ; Wei SONG ; Samah Attia ALGHARIB ; Wei CHEN
Journal of Veterinary Science 2022;23(1):e1-
Background:
The poor bioadhesion capacity of tilmicosin resulting in treatment failure for Staphylococcus aureus small colony variants (SASCVs) mastitis.
Objectives:
This study aimed to increase the bioadhesion capacity of tilmicosin for the SASCVs strain and improve the antibacterial effect of tilmicosin against cow mastitis caused by the SASCVs strain.
Methods:
Tilmicosin-loaded chitosan oligosaccharide (COS)-sodium carboxymethyl cellulose (CMC) composite nanogels were formulated by an electrostatic interaction between COS (positive charge) and CMC (negative charge) using sodium tripolyphosphate (TPP) (ionic crosslinkers). The formation mechanism, structural characteristics, bioadhesion, and antibacterial activity of tilmicosin composite nanogels were studied systematically.
Results:
The optimized formulation was comprised of 50 mg/mL (COS), 32 mg/mL (CMC), and 0.25 mg/mL (TPP). The size, encapsulation efficiency, loading capacity, polydispersity index, and zeta potential of the optimized tilmicosin composite nanogels were 357.4 ± 2.6 nm, 65.4 ± 0.4%, 21.9 ± 0.4%, 0.11 ± 0.01, and -37.1 ± 0.4 mV, respectively; the sedimentation rate was one. Scanning electron microscopy showed that tilmicosin might be incorporated in nano-sized crosslinked polymeric networks. Moreover, adhesive studies suggested that tilmicosin composite nanogels could enhance the bioadhesion capacity of tilmicosin for the SASCVs strain. The inhibition zone of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels were 2.13 ± 0.07, 3.35 ± 0.11, and 1.46 ± 0.04 cm, respectively. The minimum inhibitory concentration of native tilmicosin, tilmicosin standard, and tilmicosin composite nanogels against the SASCVs strain were 2, 1, and 1 µg/mL, respectively. The in vitro time-killing curves showed that the tilmicosin composite nanogels increased the antibacterial activity against the SASCVs strain.
Conclusions
This study provides a potential strategy for developing tilmicosin composite nanogels to treat cow mastitis caused by the SASCVs strain.
10.Clinical and CT imaging features of immune checkpoint inhibitor-associated pneumonia
Wenping LI ; Pengju ZHANG ; Jinhuan XU ; Wei WANG ; Xiang YAN ; Yang XU ; Shaohong ZHAO
Chinese Journal of Radiology 2022;56(12):1352-1358
Objective:To explore the clinical and CT imaging features of immune checkpoint inhibitor-associated pneumonia (CIP) and to improve the early diagnostic ability of CIP.Methods:From June 1, 2020 to October 31, 2021, the clinical data and chest CT images of 2 067 patients with advanced malignant tumor treated with immune checkpoint inhibitor (ICI) in the First Medical Center, Chinese PLA General Hospital were retrospectively analyzed. Patients with CIP were enrolled according to the guidelines for CIP diagnosis, and the incidence, time from the start of medication to the onset of CIP, medication cycle, imaging features, imaging patterns, CT grade and outcomes were analyzed. χ 2 test was used to compare the incidence of CIP in patients with or without basic lung disease. Results:Among 2 067 patients with malignant tumors treated with ICI, 67 patients developed CIP, the incidence of CIP was 3.2%. The incidence of CIP was significantly different between 386 patients with basic lung disease (7.00%, 27/386) and 1 681 patients without basic lung disease (2.4%, 40/1 681) (χ 2=21.32, P<0.001). The time from the start of medication to the onset of CIP was 7-367 d (median 52 days), and the duration of medication was 1-12 cycles (median 2 cycles). The imaging features of CIP presented as ground glass opacities in 54 cases (80.6%), solid nodules in 26 cases (38.8%), consolidations in 25 cases (37.3%) and irregular reticular opacities in 24 cases (35.8%). The main radiologic pattern was organizing pneumonia (OP, 34 cases, 50.7%), and followed by diffuse alveolar damage (DAD) pattern (14 cases, 20.9%). According to CT grading, there were 26 cases in low risk grade, 17 cases in moderate risk grade and 24 cases in high risk grade. Of 43 low-and medium-risk grade cases, 25 were OP pattern, accounting for 58.1%, and among 24 high-risk grade patients, 13 were DAD pattern, accounting for 54.2%. Forty-three of the 52 patients were initially untreated, of which 23 patients progressed, 17 had lesion shrinkage, and 3 had resolution, and relapsed in 8 cases after resolution or drug withdrawal. Conclusions:The imaging manifestations of CIP are mainly ground glass opacities, nodules, consolidations, and irregular reticular opacities. The radiologic patterns are mainly OP and DAD. OP is the most common pattern in low-moderate risk grade CIP and DAD is the most common pattern in high risk grade CIP. Patients with basic lung disease are more likely to get CIP.

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