1.Dosimetric analysis of radiation pneumonitis induced by 125I seed implantation for the treatment of malignant lung tumors
Ke XU ; Jinxin ZHAO ; Zezhou LIU ; Yansong LIANG ; Guohui CAO ; Xiaoli LIU ; Yan DI ; Juan WANG ; Hongtao ZHANG
Chinese Journal of Radiological Medicine and Protection 2024;44(1):13-17
Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.
2.Effect and mechanism of casticin on wound healing in rats with superficial second-degree burn
Guohui ZHANG ; Haibo ZHANG ; Dongsheng CAO
China Pharmacy 2024;35(21):2603-2608
OBJECTIVE To explore the mechanism by which casticin (CAS) promotes wound healing in superficial second- degree burned rats through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS Rats were randomly assigned to a control group (physiological saline), a model group (5% sodium carboxymethyl cellulose blank matrix), low- and high-dose CAS groups (15 mL of CAS solution at concentrations of 30 and 60 mmol/L, respectively), a high dose CAS plus LY294002 group [a mixture of 15 mL CAS solution (60 mmol/L) and PI3K inhibitor LY294002 solution (20 μmmol/L)], and a positive control group (thick application of Jingwanhong ointment 0.5-1.0 cm), with 15 rats in each group. Except for the control group, the other groups were subjected to a superficial second-degree burn rat model by igniting a mixture of burn fuel on the skin surface, and the administration was applied topically within two hours after the burn. After 28 days of administration, the wound healing rate of the burned rats was calculated, the histopathological changes in the central tissue of the rat’s burned wound were observed, and the levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL- 1β), IL-6, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) in the serum of rat were detected. The phosphorylation levels of related proteins in the PI3K/AKT/mTOR signaling pathway in the burned tissue of the rats were also detected. RESULTS Compared with the control group, the rats in the model group showed epidermal and superficial dermal damage in skin tissue, poor healing status, inflammatory cell infiltration, and incomplete tissue structure. The levels of IL-6, IL-1β, TNF-α, MMP-2 and MMP-9 in the serum were significantly increased (P<0.05), and the levels of VEGF in the serum and the phosphorylation levels of E-mail:caodongsheng@ahmu.edu.cn PI3K, AKT, mTOR proteins in the central tissue of the burned wound were significantly decreased (P<0.05). Compared with the model group, the pathological changes and the levels of the above indicators in the serum and central tissue of the burned wound in the CAS low- and high-dose groups were significantly reversed (P<0.05), and the changes in the CAS high-dose group were significantly more pronounced than those in the CAS low- dose group (P<0.05). The addition of the PI3K inhibitor LY294002 could reverse the promoting effect of CAS on the wound healing of superficial second-degree burned rats (P<0.05). CONCLUSIONS CAS can promote the healing of superficial second- degree burned wounds in rats, and its mechanism of action may be related to the activation of the PI3K/AKT/mTOR signaling pathway.
3.Effectiveness and safety of autologous fat particle transplantation in facial rejuvenation: a meta analysis
Zhiming CAO ; Lilin FANG ; Junyi ZHANG ; Xiaoen ZHANG ; Guohui WU ; Qingni TU
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(6):598-602
Objective:To explore the effectiveness and safety of autologous fat granule transplantation for facial rejuvenation.Methods:Databases including PubMed, Cochrane Library, Google Scholar, Web of Science, China Biology Medicine Database, Wanfang Database, and CNKI were searched. The search time range was from 2013 to 2023. Search key words included autologous fat transplantation, facial rejuvenation, efficacy, effectiveness, safety, complications, etc. Meta-analysis was used. Literature search was conducted by using tool method and forward search method. OR (95% CI) was used as the statistical measure for efficacy analysis. Heterogeneity of literature was tested by I2 test. Publication bias was tested by Begg′ s test. Results:A total of 23 literatures were included, covering 2 852 beauty seekers. There was no significant publication bias. The satisfactory rate of beauty seekers after autologous granular fat transplantation was relatively high ( OR=0.95, 95% CI: 0.91-0.97). The success rate of one-time injection was relatively high ( OR=0.79, 95% CI: 0.73-0.84). The incidence of postoperative complications was relatively low ( OR=0.02, 95% CI: 0.01-0.04). Conclusion:Autologous fat granule transplantation surgery has good effectiveness and safety for facial rejuvenation.
4.Correlation between serum human epididymis protein 4 levels and proteinuria in type 2 diabetes patients
Chunyan BO ; Shipei ZHANG ; Jinshen CHU ; Guohui XUE ; Fang WAN ; Junda CAO ; Keqi CHEN ; Jing CHEN ; Xiaofeng LIU ; Xueli CHEN
China Modern Doctor 2024;62(33):1-5
Objective To investigate the correlation of human epididymis protein 4(HE4)with proteinuria in patients with type 2 diabetes mellitus(T2DM).Methods A total of 147 T2DM patients from January 2020 to July 2023 in Jiujiang NO.l People's Hospital were enrolled in observation group.According to the severity of proteinuria,observation group was divided into three groups:Normal albuminuria group(101 cases),microalbuminuria group(25 cases),and massive albuminuria group(21 cases).50 healthy examinees with gender and age matching during the same period were selected as control group.HE4 levels and clinical indicators in each group were compared and analyzed.Correlation between HE4 and proteinuria was analyzed by using univariate and multivariate linear regression.Results The correlation network diagram reveals that HE4 functions was a pivotal node linking serum albumin,urinary microalbumin,urinary microalbumin-to-creatinine ratio(UACR),and renal function biomarkers.Compared to control group,HE4 levels significantly elevated in observation group(P<0.01).Both univariate and multivariate linear regression analysis demonstrate a positive correlation between HE4 and UACR.Logistic regression analysis shew that after adjusting for confounding factors including age,gender,estimated glomerular filtration rate(eGFR),albumin(ALB),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),lactate dehydrogenase(LDH)etc.elevated HE4 levels was a risk factor for proteinuria(OR=1.110,95%CI:1.005-1.226).Conclusion Elevated HE4 levels in patients with T2DM is positivly correlated with UACR.Increase its level increases the risk of proteinuria in T2DM patients.
5.Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns
Yan LIANG ; Wen SHI ; Yang SHAO ; Xinzhuang LIU ; Hongmin GONG ; Guohui CAO ; Cong GAO ; Naijun XIN ; Guodong SONG
Chinese Journal of Burns 2024;40(4):348-357
Objective:To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns.Methods:This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing.Results:Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group ( Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups ( P>0.05). Conclusions:For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.
6.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.
7.Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023)
Yan HU ; Dongliang WANG ; Xiao CHEN ; Zhongmin SHI ; Fengjin ZHOU ; Jianzheng ZHANG ; Yanxi CHEN ; Liehu CAO ; Sicheng WANG ; Jianfei WANG ; Hongliang WANG ; Yong FENG ; Zhimin YING ; Chengdong HU ; Qinglin HAN ; Ming LI ; Xiaotao CHEN ; Zhengrong GU ; Biaotong HUANG ; Liming XIONG ; Yunfei ZHANG ; Zhiwei WANG ; Baoqing YU ; Yong WANG ; Lei ZHANG ; Lei YANG ; Peijian TONG ; Ximing LIU ; Qiang ZHOU ; Feng NIU ; Weiguo YANG ; Wencai ZHANG ; Shijie CHEN ; Jinpeng JIA ; Qiang YANG ; Tao SHEN ; Bin YU ; Peng ZHANG ; Yong ZHANG ; Jun MIAO ; Kuo SUN ; Haodong LIN ; Yinxian YU ; Jinwu WANG ; Kun TAO ; Daqian WAN ; Lei WANG ; Xin MA ; Chengqing YI ; Hongjian LIU ; Kun ZHANG ; Guohui LIU ; Dianying ZHANG ; Zhiyong HOU ; Xisheng WENG ; Yingze ZHANG ; Jiacan SU
Chinese Journal of Trauma 2023;39(4):289-298
Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
8.Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection (version 2023)
Chenchen YAN ; Bobin MI ; Wu ZHOU ; Faqi CAO ; Yun SUN ; Mengfei LIU ; Yiqiang HU ; Guandong DAI ; Dianying ZHANG ; Guodong LIU ; Zhiyong HOU ; Kun ZHANG ; Bin YU ; Jinmin ZHAO ; Xinlong MA ; Xieyuan JIANG ; Xinbao WU ; Jican SU ; Peifu TANG ; Baoguo JIANG ; Yingze ZHANG ; Guohui LIU
Chinese Journal of Trauma 2023;39(4):309-317
As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.
9.Modified arthroscopic Brostr?m procedure for the treatment of chronic ankle instability combined with multiple ligament laxity
Yan XU ; Deyu DUAN ; Guohui LIU ; Cao YANG ; Liu OUYANG
Chinese Journal of Trauma 2023;39(4):349-353
Objective:To investigate the effectiveness of modified arthroscopic Brostr?m procedure for the treatment of chronic ankle instability combined with multiple ligament laxity.Methods:A retrospective case series study was used to analyze the clinical data of 26 patients with chronic ankle instability combined with multiple ligament laxity treated at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2016 to December 2020, including 10 males and 16 females; aged 18-48 years [(27.5±7.1)years]. All patients underwent arthroscopic repair of the anterior talofibular ligament (ATFL) by the modified Brostr?m procedure. Healing of surgical incisions was observed after operation. The change of talus tilt angle for ankle stability evaluation, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score for ankle function evaluation, and the visual analogue score (VAS) for pain evaluation were assessed before operation, at 3 months postoperatively and at the last follow-up. Complications were observed.Results:All patients were followed up for 18-47 months [(25.3±8.5)months]. All surgical incisions were healed at stage I. The talus tilt angle was decreased from preoperative (15.6±4.7)° to (4.1±1.3)° and (3.5±0.9)° at 3 months postoperatively and at the last follow-up (all P<0.01). The AOFAS ankle-hindfoot score was improved from preoperative (65.8±14.5)points to (86.5±5.6)points and (93.4±4.2)points at 3 months postoperatively and at the final follow-up (all P<0.01). The VAS was decreased from preoperative 3.0 (2.0, 4.0)points to 1.5 (0.0, 2.0)points and 1.0 (0.0, 1.2)points at 3 months postoperatively and at the last follow-up (all P<0.01). Significantly higher AOFAS ankle-hindfoot score and lower VAS were found at the final follow-up when compared with the scores at 3 months postoperatively (all P<0.05). One patient developed superficial peroneal nerve injury, which was recovered spontaneously without special treatment. Conclusion:For chronic ankle instability combined with multiple ligament laxity, the modified arthroscopic Brostr?m procedure has advantages of improved ankle stability, good ankle function recovery, obvious pain relief and less postoperative complications.
10.Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023)
Yuan XIONG ; Bobin MI ; Chenchen YAN ; Hui LI ; Wu ZHOU ; Yun SUN ; Tian XIA ; Faqi CAO ; Zhiyong HOU ; Tengbo YU ; Aixi YU ; Meng ZHAO ; Zhao XIE ; Jinmin ZHAO ; Xinbao WU ; Xieyuan JIANG ; Bin YU ; Dianying ZHANG ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Qikai HUA ; Mengfei LIU ; Yiqiang HU ; Peng CHENG ; Hang XUE ; Li LU ; Xiangyu CHU ; Liangcong HU ; Lang CHEN ; Kangkang ZHA ; Chuanlu LIN ; Chengyan YU ; Ranyang TAO ; Ze LIN ; Xudong XIE ; Yanjiu HAN ; Xiaodong GUO ; Zhewei YE ; Qisheng ZHOU ; Yong LIU ; Junwen WANG ; Ping XIA ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Dongliang WANG ; Fengfei LIN ; Jiangdong NI ; Aiguo WANG ; Dehao FU ; Shiwu DONG ; Lin CHEN ; Xinzhong XU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Yingze ZHANG ; Xiaobing FU ; Guohui LIU
Chinese Journal of Trauma 2023;39(6):481-493
Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

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