1.Effect of preoperative oral ibuprofen on postoperative pain after dental implantation: a randomized controlled trial
Kang GAO ; Xuezhu WEI ; Bin ZHAO ; Zhiguang LIU ; Conglin DU ; Xin WANG ; Yao WANG ; Changying LIU ; Dezheng TANG ; Qi ZHANG ; Ruiqing WU ; Mingming OU ; Wei LI ; Qian CHENG ; Yilin XIE ; Pan MA ; Jun LI ; Hao WANG ; Zuomin WANG ; Su CHEN ; Wei ZHANG ; Jian ZHOU
Chinese Journal of Stomatology 2024;59(8):777-783
Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.
2.Quantitative analysis of macular structure and microvascular changes in patients with diabetic macular ischemia
Changying LIU ; Lingna LI ; Meizi GAO ; Xuzheng ZHAO
Chinese Journal of Ocular Fundus Diseases 2024;40(2):116-121
Objective:To observe the changes of macular structure and microvessels in eyes with diabetes macular ischemia (DMI).Methods:A retrospective case study. From January 2023 to July 2023, 23 patients of 31 eyes diagnosed with DMI at Tangshan Ophthalmological Hospital were included in this study. Among them, there were 14 males with 23 eyes; Female cases with 8 eyes. Age were (59.5±4.6) years old. According to the DMI grading standard formulated by the research group for early treatment of diabetes retinopathy, the patients were divided into mild DMI group, moderate DMI group, and severe DMI group, with 8, 12, and 11 eyes respectively. The blood flow density (VD), perfusion area (FA), small vessel VD (SVD), inner retinal capillary plexus VD, FA, and outer retinal, choroidal, and ganglion cell complex (GCC) thickness within 1 mm of the macular fovea in retinal superficial vascular plexus (SVP)were measured using a scanning frequency light source optical coherence tomography instrument. The changes in macular structure and microvasculature in the affected eyes of different degrees of DMI groups were compared and observed. Inter group comparisons were conducted using one-way ANOVA or Kruskal Wallis H-test. Spearman correlation analysis was used to analyze the correlation between DMI severity and GCC, outer retina, choroid thickness, VD, FA and SVP VD, SVD and FA in inner retina. Results:The GCC ( F=70.670), outer retinal thickness ( H=12.393), VD ( F=105.506), SVD ( H=25.300), FA ( F=107.655), and VD ( H=24.098) and FA ( H=25.300) of the retinal SVP in the mild, moderate, and severe DMI groups were compared, and the differences were statistically significant ( P<0.05). There was no statistically significant difference in choroidal thickness ( H=2.441, P>0.05). Pairwise comparison between groups: VD, SVD, FA of GCC thickness and SVP, and VD of inner retina were statistically significant between severe DMI group and moderate DMI group, and between moderate DMI group and mild DMI group ( P<0.05). The thickness of outer retina was statistically significant between severe DMI group and moderate DMI group ( P<0.05). Inner retinal FA: there were statistically significant differences between severe DMI group, moderate DMI group and mild DMI group ( P<0.05). The correlation analysis results showed that GCC ( r s=-0.918), outer retinal thickness ( r s=-0.448), and inner retinal VD ( r s=-0.894) and FA ( r s=-0.918), as well as VD ( r s=-0.919), SVD ( r s=-0.924), and FA ( r s=-0.939) of retinal SVP, were all negatively correlated with the degree of DMI ( P<0.05). There was no correlation between choroidal thickness and degree of DMI ( r s=-0.081, P>0.05). Conclusion:The thickness of GCC, outer retina and choroid, the VD, SVD, and FA of the retinal SVP, the VD and FA of inner retina are all reduced in eyes with different degrees of DMI, while all of them are negatively correlated with the degree of DMI, except for choroid thickness.
3.Correlation between preoperative coronary angiography and postoperative acute kidney injury in cardiac surgery: A retrospective study in a single center
Changying ZHAO ; Yang YAN ; Tao SHI ; Yongxin LI ; Jing LI ; Wenyan LIU ; Miaomiao LIU ; Xinglong ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1820-1825
Objective To explore the relationship between preoperative coronary angiography and postoperative acute kidney injury (AKI) in cardiac surgery. Methods The clinical data of patients who underwent coronary angiography within 30 days before cardiac surgery in the First Affiliated Hospital of Xi’an Jiaotong University from January 2015 to April 2019 were retrospectively analyzed. Univariate analysis and multivariate logistic regression analyses were used to explore the relationship between the interval from preoperative coronary angiography to cardiac surgery and postoperative AKI. Results Finally 1 112 patients were collected, including 700 males and 412 females, with a median age of 61 (55, 66) years. The incidence of postoperative AKI was 40.8% (454/1 112), of which grade 2-3 AKI accounted for 11.9%. Multivariate analysis showed that age (OR=1.049, 95%CI 1.022-1.077, P<0.001), body mass index (OR=1.065, 95%CI 1.010-1.123, P=0.020) and time interval between preoperative coronary angiography and cardiac surgery within 24 hours (OR=1.625, 95%CI 1.116-2.364, P=0.011) were independent predictors of postoperative AKI. Patients who underwent coronary angiography within 24 hours before surgery had a 10.6% higher incidence of postoperative AKI compared to those who underwent angiography ≥24 hours before surgery (P=0.004). Patients who underwent valve surgery with or without coronary artery bypass grafting (CABG) had a higher risk of AKI than those who only underwent CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing coronary angiography within 24 hours before cardiac surgery did not prolong the length of ICU stay or hospital stay, nor did it increase the risk of death or renal failure after the operation. Conclusion Undergoing coronary angiography within 24 hours before cardiac surgery increases the risk of postoperative AKI.
4.Effect and mechanism of Qishishenshu Capsule on renal fibrosis in mouse early diabetic nephropathy
Xiaoqing LAO ; Chen CHEN ; Hongmin ZHANG ; Xiu YANG ; Jiangshan SHI ; Hongwei SU ; Hongping SHEN ; Li WANG ; Manrui YOU ; Xiaobin LI ; Changying ZHAO
Chinese Journal of Comparative Medicine 2024;34(9):56-65
Objective To investigate the therapeutic effect and underlying mechanism of Qishishenshu Capsule on renal fibrosis in mice with early diabetic nephropathy(DN).Methods A DN mouse model was established by multiple injections of streptozotocin.The mice were randomly divided into a normal group(NC),model group(DN),and Qishi group(QS)(0.9 g/(kg·d)),with eight mice in each group.Mice were gavaged continuously for 4 weeks,and fasting blood glucose(FBG)was measured weekly.Four weeks later,urinary albumin/creatinine(UACR),serum creatinine,and blood urea nitrogen were measured.Hematoxylin-eosin,periodicacid-Schiff,and Sirius red staining were used to analyze renal pathological changes.Real-time fluorescence quantitative reverse-transcription polymerase chain reaction was used to detect the mRNA levels of fibronectin(FN),collagen type Ⅰ alpha 1(Col1a1),and α-smooth muscle actin(α-SMA).Immunohistochemistry and Western blot were performed to detect FN,collagen type Ⅰ(Collagen Ⅰ),collagen typeⅢ(Collagen Ⅲ),α-SMA,Podocin,Nephrin,and transforming growth factor-β1/SMAD family member2/3(TGF-β1/Smad2/3)pathway-related proteins.Results Compared with mice in the NC group,those in the DN group showed significantly higher levels of FBG and UACR(P<0.001),and mesangial hyperplasia,basement membrane thickening,and collagen deposition in the renal tissue.The mRNA levels of FN,Col1a1,and α-SMA were increased(P<0.05).Protein levels of Podocin and Nephrin were decreased(P<0.05).The levels of FN,Collagen I,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were increased(P<0.05).Compared with the DN group,the QS group's level of UACR was decreased(P<0.05),their renal pathological injury was alleviated,and mRNA levels of FN,Collagen Ⅰ,andα-SMA were attenuated(P<0.05);whereas their protein levels of Podocin and Nephrin were elevated(P<0.05).The levels of FN,Collagen Ⅰ,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were also decreased(P<0.05).Conclusions Qishishenshu Capsule improved renal fibrosis in DN mice,probably through the inhibition of the TGF-β1/Smad2/3 signaling pathway.
5.Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion.
Hua LI ; Yong WANG ; Changying ZHAO ; Jian LIU ; Lei ZHANG ; Anyuan LI
Chinese Medical Journal 2022;135(6):707-713
BACKGROUND:
: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.
METHODS:
: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.
RESULTS:
: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.
CONCLUSIONS
: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.
Animals
;
Disease Models, Animal
;
Fecal Microbiota Transplantation
;
Gastrointestinal Microbiome/physiology*
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Mice
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RNA, Ribosomal, 16S/genetics*
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Serotonin
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Tics
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Tourette Syndrome/therapy*
6.Local recurrence pattern of pT 1-2N 1 breast cancer after modified radical mastectomy—a pooled-analysis of 5442 patients from 12 centers
Xinyuan GUO ; Yujing ZHANG ; Na ZHANG ; Yu TANG ; Xuran ZHAO ; Hao JING ; Hui FANG ; Ge WEN ; Jing CHENG ; Mei SHI ; Qishuai GUO ; Hongfen WU ; Xiaohu WANG ; Changying MA ; Yexiong LI ; Hongmei WANG ; Min LIU ; Shulian WANG
Chinese Journal of Radiation Oncology 2022;31(3):248-252
Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.
7.Application of lobed anterolateral thigh chimeric perforator flap in repairing the complex soft tissue defects of limbs
Chengwu ZANG ; Yongxiang CHEN ; Hang XIAN ; Changying ZHAO ; Jianlei ZHANG ; Qingyang ZOU ; Yule ZHU ; Rui CONG
Chinese Journal of Microsurgery 2022;45(3):254-259
Objective:To investigate the application and surgical effect of lobed anterolateral femoral chimeric perforator flap in repairing the complex soft tissue defects of limbs.Methods:Clinical materials of 52 cases with complex soft tissue defects of limbs were retrospectively reviewed from October 2013 to October 2020. Thirty-two males and 20 females were reviewed, and the age of them ranged from 6 to 65(mean 39) years old. The injuries include 17 cases of traffic accidents, 15 machine crush injuries, 12 engineering accidents, and 8 extensive resection of malignant tumors. The size of soft tissue defects ranged from 26.0 cm×10.0 cm to 35.0 cm×15.0 cm. Lobed anterolateral thigh chimeric perforator flaps or lobed Flow-through chimeric perforator flaps were designed according to the soft tissue defects and blood circulation of the distal extremities. Start from 8-month post-operation, upper limb function was assessed according to the Upper Limb Function Assessment Standard of Hand Surgery Branch of Chinese Medical Association and Disability of arm shoulder and hand(DASH) score scale, and Fugl-Meyer score system was used to evaluate the lower limb function. Long-term follow-up was conducted through WeChat video call and outpatient clinic evaluation.Results:All flaps survived. One patient with crush injury got delayed wound healing due to deep hemaetoma after surgery, and the rest were healed at the first stage. All the cases entered followed-up, ranged from 6 to 20(mean 8) months. The appearance of the flaps was satisfactory, and the color of the flaps has no significant difference compared with the recipient area. No recurrence of tumor was reported during the follow-up period. According to the Upper Limb Function Assessment Standard of Hand Surgery Branch of Chinese Medical Association, there were 21 excellent cases and 8 good cases, and the total excellent and good rate was 100%. The DASH score of upper limbs ranges from 11.5 to 45.1(mean 25.4±13.7), and the Fugl-Meyer score of lower limbs range from 18.6 to 31.8(mean 26.2±11.2) at the last follow-up.Conclusion:The complex soft tissue defect of limbs is a common complication caused by high-energy trauma, which is difficult to repair. The lobed anterolateral thigh chimeric perforator flap through a Decompose-Combine and arrange method for reconstruction, which is flexible in flap design. A variety of tissue flaps can be obtained by anastomosing only one group of blood vessels. It is an ideal choice for repairment of complex soft tissue defects of limbs.
8.Multimodal imaging features of tamoxifen retinopathy
Changying LIU ; Lingna LI ; Xuzheng ZHAO ; Huaiqiang ZHANG ; Fang CHEN
Chinese Journal of Ocular Fundus Diseases 2022;38(11):901-904
Objective:To observe the multimodal imaging characteristics of tamoxifen retinopathy.Methods:A retrospective case study. From January 2019 to December 2021, 4 patients (8 eyes) with tamoxifen retinopathy diagnosed in Tangshan Eye Hospital were included in the study. All patients were female, with sick binoculus. The age was 59.5±4.6 years. After breast cancer resection, tamoxifen 20 mg/d was taken orally consecutively, including 1, 1, and 2 cases who took tamoxifen orally for 5, 7, and ≥10 years. All eyes were examined by fundus color photography, optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and fundus autofluorescence (AF). The multi-mode image features of the fundus of the affected eyes were observed.Results:The yellow white dot crystal like material deposition in the macular area was observed in all eyes. In fundus AF examination, macular area showed patchy strong AF. FFA examination showed telangiectasia and fluorescein leakage in macular area at late stage. OCT showed that punctate strong reflexes could be seen between the neuroepithelial layers in the macular region with the formation of a space between the neuroepithelial layers, the interruption of the elliptical zone (EZ), and the formation of a hole in the outer lamella including 4, 5 and 3 eyes; The thickness of ganglion cells in macular region decreased in 7 eyes. OCTA showed that the blood flow density of the superficial retinal capillary plexus around the arch ring was decreased, and the retinal venules were dilated in 2 eyes; Deep capillary plexus (DCP) showed telangiectasia.Conclusion:Deposition of yellowish white dot like crystals can be seen in the macular region of tamoxifen retinopathy; dotted strong reflex between neuroepithelial layers, cavity formation, thinning of ganglion cell layer, EZ middle fissure and outer lamellar fissure; DCP capillaries and venules around the arch were dilated; telangiectasia in macular region; flaky strong AF in macular region.
9.Scar management after operation of congenital syndactyly of hand in children
Hang ZHANG ; Changying ZHAO ; Hang XIAN ; Chengwu ZANG ; Yongxiang CHEN ; Rui CONG
Chinese Journal of Plastic Surgery 2022;38(8):911-917
Objective:To explore the method of scar management after the operation of congenital syndactyly.Methods:The clinical data of children with congenital cutaneous skin syndactyly of the hand admitted to the Department of Orthopedics of the First Affiliated Hospital of Air Force Medical University from January 2018 to January 2020 were retrospectively analyzed. The procedures of finger dividing were performed under general anesthesia, and the fingers were bandaged in an extended position after the operation. After the incision was healed entirely, anti-scar drugs were used in conjunction with the reconstruction of the webbed with a self-adhesive soft silicone film, wrapped with a self-adhesive elastic bandage for one year, and an extended finger brace was worn for 3 to 6 months. Postoperative complications, finger shape, and appearance were followed up. At the last follow-up, family members of the children were asked to evaluate the reconstruction effect of the webbed shape, scar condition, and flexion and extension of the affected finger.Total active movement( TAM )evaluation criteria were used to evaluate the flexion and extension function of the affected finger. The Vancouver Scar Scale (VSS) was used to evaluate the postoperative cicatrix.Results:A total of 28 children with 32 syndactyly were included, including 12 males and 16 females. The age ranged from 12 to 34 months (mean, 18.3 months). The syndactyly was unilateral in 24 patients (left in 14 and right in 10) and bilateral in 4. Among all the 32 syndactyly, there were 16 cases of the middle-ring finger, 9 cases of the ring-little finger, 5 cases of the index-middle finger, and 2 cases of the thumb-index finger. All the children were followed up for 13~36 months (mean, 28.6 months). No complications such as infection and abnormal blood supply occurred in the early postoperative period. The shape and appearance of the fingers were in good condition. While using a self-adhesive soft silicone membrane, two children developed a local rash, which was improved by desensitization treatment and continued to use usually. The family members were satisfied with the shape of the reconstructed finger web, the scar, and the flexion and extension of the affected finger. TAM evaluation criteria showed a 100% excellent flexion and extension function rate. VSS showed a 100% excellent-good rate of scar status.Conclusions:After incision healing of the reconstruction surgery for pediatric congenital syndactyly, the use of anti-scar drugs, including self-adhesive elastic bandages and split-finger braces, can effectively prevent postoperative scar hyperplasia and better consolidate the treatment effect, with distinct clinical application value.
10.Scar management after operation of congenital syndactyly of hand in children
Hang ZHANG ; Changying ZHAO ; Hang XIAN ; Chengwu ZANG ; Yongxiang CHEN ; Rui CONG
Chinese Journal of Plastic Surgery 2022;38(8):911-917
Objective:To explore the method of scar management after the operation of congenital syndactyly.Methods:The clinical data of children with congenital cutaneous skin syndactyly of the hand admitted to the Department of Orthopedics of the First Affiliated Hospital of Air Force Medical University from January 2018 to January 2020 were retrospectively analyzed. The procedures of finger dividing were performed under general anesthesia, and the fingers were bandaged in an extended position after the operation. After the incision was healed entirely, anti-scar drugs were used in conjunction with the reconstruction of the webbed with a self-adhesive soft silicone film, wrapped with a self-adhesive elastic bandage for one year, and an extended finger brace was worn for 3 to 6 months. Postoperative complications, finger shape, and appearance were followed up. At the last follow-up, family members of the children were asked to evaluate the reconstruction effect of the webbed shape, scar condition, and flexion and extension of the affected finger.Total active movement( TAM )evaluation criteria were used to evaluate the flexion and extension function of the affected finger. The Vancouver Scar Scale (VSS) was used to evaluate the postoperative cicatrix.Results:A total of 28 children with 32 syndactyly were included, including 12 males and 16 females. The age ranged from 12 to 34 months (mean, 18.3 months). The syndactyly was unilateral in 24 patients (left in 14 and right in 10) and bilateral in 4. Among all the 32 syndactyly, there were 16 cases of the middle-ring finger, 9 cases of the ring-little finger, 5 cases of the index-middle finger, and 2 cases of the thumb-index finger. All the children were followed up for 13~36 months (mean, 28.6 months). No complications such as infection and abnormal blood supply occurred in the early postoperative period. The shape and appearance of the fingers were in good condition. While using a self-adhesive soft silicone membrane, two children developed a local rash, which was improved by desensitization treatment and continued to use usually. The family members were satisfied with the shape of the reconstructed finger web, the scar, and the flexion and extension of the affected finger. TAM evaluation criteria showed a 100% excellent flexion and extension function rate. VSS showed a 100% excellent-good rate of scar status.Conclusions:After incision healing of the reconstruction surgery for pediatric congenital syndactyly, the use of anti-scar drugs, including self-adhesive elastic bandages and split-finger braces, can effectively prevent postoperative scar hyperplasia and better consolidate the treatment effect, with distinct clinical application value.

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