1.Analysis of imageology appearance and clinical characteristics of the cystic and solid breast carcinoma
Shuming XU ; Linxian CHENG ; Xuanqin YANG ; Shaoling YUAN ; Lan FU
Cancer Research and Clinic 2013;25(7):448-451,454
Objective To analyze imageology appearance and clinical characteristics of the cystic and solid breast carcinoma.Methods Features of MRI and B-type ultrasonic inspection of 26 patients with the cystic and solid breast carcinoma pathologically confirmed (15 patients with mucinous carcinoma,6 patients with intracystic papillary carcinoma,5 patients with squamous cell carcinoma of the breast) were retrospectively reviewed.Results In terms of clinical appearance,the incidence of the squamous cell breast carcinoma with an average age of 70.1 years old was larger than in youth,while mucinous carcinoma with an average age of 67.7 years old and intracystic carcinoma of breast with an average age of 55.1 years old were contrary.The squamous cell breast carcinoma developed more quickly than mucinous carcinoma and intracystic carcinoma of breast.The squamous cell breast carcinoma often occurred around mammilla (4/5),while the mucinous carcinoma and intracystic papillary carcinoma often occurred upper outer quadrant of breast,which was similar with other breast cancer.The average size of 49.6 mm in the squamous cell breast carcinoma was largest than the average size of 25.1 mm in mucinous carcinoma and the average size of 35.2 mm in intracystic papillary carcinoma.The malignant degree of squamous cell breast carcinoma was higher than mucinous carcinoma and intracystic papillary carcinoma,which intended to occur lymph node metastasis and skin infiltration.The diagnosis probability of mucinous carcinoma was smaller than intracystic papillary carcinoma through preoperative puncture,while squamous cell breast carcinoma was larger.On the MRI imageology appearance,both types of breast cancer had the same shape of rotundity or lobulated.The tumors were low signal on T1WI and partially high signal on T2WI,which were circular enhancement after enhancement.However,the edge of mucinous carcinoma and squamous cell breast carcinoma was rougher than intracystic papillary carcinoma compared with squamous cell breast carcinoma.The bursa wall of mucinous carcinoma was more uniformity,while papillary soft tissue image can be found in intracystic papillary carcinoma,which was enhanced significantly after enhancement.In terms of ultrasonic sound (US),there were low echo signal and high echo signal on the back of tumor compared with other breast tumor.There were shadow beside mucinous carcinoma.Squamous cell breast carcinoma was rich in blood supply,while mucinous carcinoma and intracystic papillary carcinoma were opposite.Conclusion Histological type of cystic and solid breast carcinoma is complex,but the appearances of MRI and US have some characteristics.Histological type and the range of disease could be guessed through the combination of preoperative puncture and clinical appearance,which plays an important role in operation mode and treatment guidance.
2.Role of osteoblasts in the sense of glucose
Hongli ZHAO ; Hongqiu ZHAO ; Xiaoying FU ; Rongsen MENG ; Ying ZHANG ; Li YAN ; Hua CHENG ; Mingtong XU ; Shaoling ZHANG ; Zuzhi FU
Chinese Journal of Tissue Engineering Research 2010;14(2):201-204
BACKGROUND: Recent study showed that osteocalcin may elevate Insulin secretion and sensitivity, prevent the fat accumulation, play a role in the metablism of glucose and lipid. Undercarboxylated osteocalcin works as the main role. OBJECTIVE: To investigate the effect of different concentrations of glucose on osteoblast undercarboxylated osteocalcin. METHODS: The rib trabeculae were resected and broken, trypsinizated and washed completely by PBS. Bone surface and non-adhesive floating cells in cleaning fluid were observed with inverted microscope. Rib trabeculae was washed by DMEM culture medium once, and cultured in culture bottle. The culture liquid was replaced by new one once a week. The osteoblast was moved from the scledte a week later. The cells were fused monolayer and could be subcultured 4 to 6 weeks later. The active second or third generation cells were inoculated to 6-pore plate forming 5 groups. Osteoblast were stimulated by 5.6 mmol/L., 7.6 mmol/L, 9.6 mmol/L, 12.6 mmol/L, 20.6 mmol/L glucose medium respectively after the 80% cells were fused, the vitamin K_2 was added into the culture liquid until the concentration of it to be 10~(-5) mol/L. Supernatant was collected after half hour culturing, the undercarboxylated osteocalcin level were detected with RIA test kit, and corrected it as the total the undercarboxylated osteccalcin, calculated the carboxylated incomplete osteocalcin rate. RESULTS AND CONCLUSION: The rate of ostecblast carboxylated incomplete osteocalcin was different under different concentration glucose. The rate of 7.6 mmol/L, 9.6 mmol/L, 20.6 mmol/L concentration glucose groups were higher than that of 5.6 mmol/L glucose group [(0.27±0.02)%, (0.29±0.04)%, (0.12±0.02)%, P < 0.05]. It is indicated that osteoblast could sense the change of glucose concentration by regulating the secretion of the undercarboxylated osteocalcin between the concentration of 5.6mmol/L to 9.6mmol/L, while the carboxylated incomplete osteocalcin decreased as the concentration of glucose increased.
3.Association between activity of nuclear factor-kappa B and angiotensin system in renal tissues of diabetic rats
Helin DING ; Ying GUO ; Mingtong XU ; Shaoling ZHANG ; Lihong CHEN ; Feng LI ; Zhenyu ZHU ; Yiqun DENG ; Zuzhi FU
Chinese Journal of Tissue Engineering Research 2006;10(20):184-186
BACKGROUND: Nowadays, angiotensin Ⅱ plays an important role in onset of diabetic nephropathy. Therefore, the nuclear factor-κB may have adjustive effects on angiotonin system of kidney tissue of diabetic rats. OBJECTIVE: To observe the relationship of activity of inhibitive nuclear factor-κB with angiotensin Ⅱ and its type 1 receptor mRNA expression of renal tissue of diabetic rats. DESIGN: Completely randomized group design, control experiment. MATERIALS: The experiment was conducted at the Experimental Animal Center, Sun Yat-sen University of Medical Sciences between March and April 2000. Fifty-one pure breed clean grade male Wistar rats were select ed. METHODS: ①Models were established in 39 rats. Streptozotocin dissolv ing in citric acid buffer (0.1 mmol/L,pH=4.5) were given to establish dia betic models with 60 mg/kg intraperitoneal injection. If the fasting blood glucose maintained above 13.9 mmol/L, the establishment of models was successful. The thirty-nine rats were randomly assigned into 3 groups: model group (n=17, without other interventional measure, feeding normally) and pyrrolidine dithiocar2. Bamate (PDTC) (active inhibitor of nuclear fac tor-κB) interventional group [n=22, PDTC at the dose of 20 mg/kg were given with intraperitoneal injection, twice a day]. Other 12 rats were as normal control group, did not make into diabetic models with normal breeding. ②After feeding for 18 weeks kidneys were got in every group. The activity of nuclear factor-κB was detected with electrophoretic mobility shift assay. The expression of type 1 receptor mRNA of angiotensin Ⅱ was measured with reverse transcription polymerase chain reaction (RT-PCR). Contents of angiotonin Ⅰ and angiotensin Ⅱ were tested with Radio Im munoassay (RIA). Activity of rennin was referred to that the result of the level of angiotonin Ⅰ at 37 ℃ water bath subduced to that at 4 ℃. ③Dif ference of measurement data was compared with single factor analysis of variance. After normal transformation, the non-normal distribution data were conducted with statistical disposal. MAIN OUTCOME MEASURES: Comparison of contents of angiotensin Ⅰ and Ⅱ, activities of rennin and nuclear factor-κB and expression of type 1 receptor mRNA of angiotensin Ⅱ in renal tissues of rats of each group. RESULTS: In the normal control group, model group and PDTC interven tional group 1, 6 and 13 rats were dropped out, respectively, so 11, 11 and 9 rats in each group were involved in the result analysis. ①Activity of nu clear factor-κB: It was higher significantly in the model group than that in the normal control group and PDTC interventional group (P < 0.01 ). It was similar between the normal control group and the PDTC interventional group. ②Activity of rennin of renal tissue: It was similar among the 3 groups. ③Content of angiotonin Ⅰ of renal tissue: It was higher obviously in the model group that that in the normal control group and the PDTC interventional group (P < 0.01 ). ④Content of angiotensin Ⅱ in renal tissue: It was similar between the model group and the normal control group. It was lower markedly in the PDTC interventional group than that in the model group and the normal control group (P < 0.01 ). Expression of type 1 receptor mRNA of angiotensin Ⅱ: It was lower remarkably in the model group than that in the normal control group (P < 0.01 ). It was lower dis tinctly in the PDTC interventional group than that in the model group and the normal control group (P < 0.01 ). CONCLUSION: The increase of activity of nuclear factor-κB in renal tissue of diabetic rats can inhibit the activity of nuclear factor-κB, which will induce the reduction of the level of angiotensin Ⅱ and expression of type 1 receptor mRNA of angiotensin Ⅱ in renal tissue of diabetic rats.
4.Association of GSTT1, GSTMI and GSTP1 gene polymorphism with aristolochic acid nephropathy
Xiaojie NI ; Shaoling ZHENG ; Feifei XU ; Mei SUN ; Yirong YANG ; Jing FU ; Bicheng CHEN ; Xiaodong PAN ; Jianjian ZHENG
Chinese Journal of Nephrology 2008;24(9):614-618
Objective To investigate the association of genetic polymorphisms in glutathione S-transferases T1 (GSTrl), M1 (GSTM1) and P1 (GSTP1) with aristolochic acid nephropathy (AAN) of Chinese people in Wenzhou of China. Methods Fifty-nine patientswith AAN (AAN group) including 29 male and 30 female as well as 157 healthy ethnically matched controls (control group) including 93 male and 64 female were enrolled in this study. The genotypes of GSTT1, GSTMI and GSTP1 were determined by multiple PCR and confronting two-pair primers PCR (CTPP-PCR). Results The genotype frequencies of GSTP1 were in Hardy-Weinberg equilibrium. Compared with the healthy controls, the frequency of GSTT1 null genotype was significantly higher in the patients with AAN (66.1% vs 48.4%,P<0.05). Risk of A.AN for individuals with GSTT1 null genotype was 1.747 fold of those without GSTIl null genotype (95% CI=0.818-3.731). The frequency of GSTM1 null genotype, GSTP1 variant genotypes and GSTP1 G allele in the patients and in the controls were 40.7%, 28.8%, 16.1% and 47.8%, 31.8%, 17.5%, respectively, which were not significantly different. No significant differences were found in prevalence of GSTM1 and GSTP1 gene distribution between patients and controls. Conclusion GSTrl gene polymorphism appears to be associated with susceptibility to AAN in Southern China.
5.Evaluation of hepatic fibrosis using Aspartate aminotransferase-to-Platelet Ratio Index in children with biliary atresia
Kankan GAO ; Zhengrong CHEN ; Xiaofang PENG ; Jie FU ; Lijuan HE ; Zhe WEN ; Shuyin PANG ; Hui WANG ; Liyuan YANG ; Shaoling GUO ; Haiying LIU
Chinese Journal of Laboratory Medicine 2015;(5):337-340
Objective To investigate the correlation between the degree of liver fibrosis and Aspartate aminotransferase-to-Platelet Ratio Index ( APRI ) in children with biliary atresia ( BA ) , and evaluate the clinical significance of liver fibrosis in biliary atresia.Methods A total of 97 patients with diagnosed BA were recruited between January 2010 and June 2013.AST, PLT and APRI were determined one week before laparotomy.The severity of hepatic tibrosis was.Judged by Metavir system the correlation among AST, PLT, APRI and severity of liver fibrosis were evaluated, and their diagnostic value for degree of liver fibrosis was analyzed by ROC.Results Sera AST levels and PLT counts of BA patients were found to be positively(r=0.367, P<0.01) and negatively(r=-0.403, P<0.01) correlated with Metavir scores of liver fibrosis, respectively.There existed positive correlation between APRI and the severity of hepatic fibrosis (r=0.541, P<0.01).The area under ROC curve of APRI to diagnose none or mild fibrosis and moderately severe fibrosis was 0.78, with sensitivity of 77.9%and specificity of 62.1%at the optimal cut-off value of 0.75; the area under ROC curve of APRI to diagnose moderately severe fibrosis with liver cirrhosis arrived 0.85, with sensitivity of 75.0% and specificity of 89.4% at the optimal cut-off value of 1.77.The accuracy of none or mild fibrosis, moderate fibrosis and cirrhosis diagnosed by APRI were 73.2%, 64.9%, 87.6%, respectively.Conclusion APRI can be used as a non-invasive parameter to assess the severity of hepatic fibrosis with BA.
6.Research progress of HyproCure subtalar stabilization in flat foot
International Journal of Surgery 2022;49(2):128-133
Flatfoot is a deformity related to the collapse of the medial arch of the foot, heel valgus and forefoot abduction. The etiology and treatment plan are affected by many factors. Conservative treatment can be given in the early stage. When conservative treatment reaches a certain time and fails to improve symptoms, surgical treatment is required. Among them, HyproCure subtalar stabilization is a new minimally invasive surgical method, which has been popularized in recent years. It has remarkable effect in correcting deformities. Because the morphological design of HyproCure is more suitable for the tarsal sinus, it can enable the subtalar joint to carry out normal three-dimensional activities without excessive correction or restriction of foot movement. Compared with the traditional surgical method, it has the advantages of small incision It has the characteristics of simple operation and less postoperative complications, and can partially replace calcaneal osteotomy. By reviewing the recently published literature, this paper reviews the advantages of subtalar stabilization and the limitations compared with traditional surgery.
7.Contribution of the absence of aspartic acid at position 57 of the HLA-DQ β chain to predisposition to insulin-dependent diabetes mellitus in a Southern Chinese population
Shaoling ZHANG ; Hua CHENG ; Zuzhi FU ; Guangshu ZHONG ; Tang YAN
Chinese Medical Journal 1998;111(8):694-697
Objective To investigate the association of the absence or presence of aspartic acid at position 57 of the HLA-DQ β chain (NA or A) with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM) in a Southern Chinese population.Methods Sixty-nine IDDM patients and 47 healthy controls in a Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR).Results The frequencies of NA and A were 64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects respectively (RR for NA was 2.68, P<0.01). The frequencies of NA/NA, NA/A and A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0% and 51.1% in the controls respectively (P<0.01). The frequency of A/A phenotype was significantly lower in the IDDM patients than in the control subjects (RR=0.22, P<0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients than in control subjects. The younger the age of IDDM onset, the higher the allele frequencies of DQB1* 0201 and DQB1* 0302.Conclusion The present study suggests that the NA confers the susceptibility to IDDM, while the A confers the protection against IDDM in patients of Southern Chinese origin. These associations are more clearcut in childhood-onset IDDM patients.
8.Efficacy and safety of single high-dose versus multiple low-dose ATG-Fresenius induction in de novo renal transplantation
Liping CHEN ; Chunbai MO ; Jun TIAN ; Guanghui PAN ; Changxi WANG ; Jianghua CHEN ; Tao LIN ; Xiaodong ZHANG ; Yaowen FU ; Long LIU ; Zhishui CHEN ; Aimin ZHANG ; Minzhuan LIN ; Xuyong SUN ; Jinsong CHEN ; Hang LIU ; Shaoling ZHENG ; Tongyu ZHU ; Qingshan QU ; Bingyi SHI
Chinese Journal of Organ Transplantation 2017;38(11):665-670
Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24% vs.23.08%).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07% vs.21.37%).There was no significant difference in the incidence of DGF between SD group and MD group (12.07% vs.6.84%,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55% vs.98.29%,P =0.6714;94.83% vs 98.29%,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.
9.Arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot
Shaoling FU ; Wenqi GU ; Xueqian LI ; Cheng CHEN ; Cheng WANG ; Guoxun SONG ; Jieyuan ZHANG ; Jian ZOU ; Jianfeng XUE ; Yan SU ; Guohua MEI ; Zhongmin SHI
Chinese Journal of Trauma 2022;38(8):693-700
Objective:To evaluate the short-term outcome of arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot.Methods:A retrospective cohort study was conducted to analyze the clinical data of 12 patients suffering chronic lateral ankle instability combined with subtle cavus foot admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from November 2016 to November 2020, including 5 males and 7 females, aged 16-62 years [(40.3±15.1)years]. All patients were treated with arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy. The calcaneal pitch angle, Meary′s angle and medial cuneiform height on the foot weight-bearing lateral view plus calcaneus valgus angle on the hindfoot long axial view were compared to evaluate the improvement of bony structure and foot alignment preoperatively and at 3 months and 1 year postoperatively. At the same time, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the improvement of ankle function and pain. Postoperative complications were also observed and recorded.Results:All patients were followed up for 1-3 years [(1.6±0.6)years]. The calcaneal pitch angle was decreased from (24.6±5.3)° preoperatively to (22.5±4.9)° at postoperative 3 months and (22.3±5.0)° at postoperative 1 year; the Meary′s angle was decreased from 6.6°(5.2°,7.6°) preoperatively to 2.5°(0.5°,3.8°) at postoperative 3 months and 2.1°(0.5°,3.2°) at postoperative 1 year; the medial cuneiform height was decreased from (24.3±5.3)mm preoperatively to (22.3±4.8)mm at postoperative 3 months and (22.3±4.6)mm at postoperative 1 year; the calcaneus valgus angle was increased from -7.1°(-10.3°,-5.9°) preoperatively to 2.3°(-2.5°,4.5°) at postoperative 3 months and 2.4°(-1.6°,3.8°) at postoperative 1 year (all P<0.01). However, there were no significant differences in the calcaneal pitch angle, Meary′s angle, medial cuneiform height, and calcaneus valgus angle at postoperative 3 months and 1 year (all P>0.05). AOFAS ankle-hindfoot score was increased from (66.8±8.7)points preoperatively to (81.0±5.9)points at postoperative 3 months and (88.6±3.6)points at postoperative 1 year (all P<0.01). According to AOFAS ankle-hindfoot score, the results were excellent in four patients and good in eight patients at postoperative 1 year, with the excellent and good rate of 100%. VAS was decreased from 2.5(2.0,4.0)points preoperatively to 2.0(1.3,2.8)points at postoperative 3 months and 1.0(0,2.0)points at postoperative 1 year (all P<0.01). There were significant differences in the AOFAS ankle-hindfoot score and VAS at postoperative 3 months and 1 year (all P<0.05). Wound malunion was seen in one patient, and healed with a dress changing. All patients had no complications such as vascular or nerve injury. There was no recurrence of malformation or joint instability during 1-year follow-up. Conclusion:For chronic lateral ankle instability combined with subtle cavus foot, arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy can stabilize ankle joint, correct hindfoot alignment, improve function and relieve pain.
10.Posterior ankle arthroscopic microfracture with platelet-rich plasma injection for the treatment of osteochondral lesions of the talus
Cheng CHEN ; Shaoling FU ; Xueqian LI ; Cheng WANG ; Guohua MEI ; Yan SU ; Jianfeng XUE ; Jian ZOU ; Jieyuan ZHANG ; Wenqi GU ; Guoxun SONG ; Zhongmin SHI
Chinese Journal of Trauma 2022;38(8):701-707
Objective:To investigate the efficacy of posterior ankle arthroscopic microfracture with platelet-rich plasma (PRP) injection for the treatment of posterior osteochondral lesions of the talus (OLT).Methods:A retrospective case series study was conducted on clinical data of 13 patients with posterior OLT admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from September 2019 to October 2020. There were 10 males and 3 females, aged 10-65 years [(38.2±15.9)years]. According to Hepple′s classification, four patients were with type II, three with type IV, and six with type V. According to Elias′ grid scheme, nine patients were in zone 7 and four patients in zone 9. The disease duration was 13-51 months [(26.2±11.4)months]. All patients underwent posterior ankle arthroscopic microfracture with PRP injection. The operation time was recorded. The visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle range of motion (ROM) were compared before operation and at 3 months and 1 year after operation. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used to evaluate the repair of cartilage injury at 1 year after operation. Complications were recorded.Results:All patients were followed up for 12-25 months [(15.7±3.7)months]. The operation time ranged from 50 to 90 minutes [(63.8±13.3)minutes]. The VAS improved from 3.0(3.0, 4.0)points before operation to 1.0(0, 2.0)points at 3 months after operation and 1.0(0,1.5)points at 1 year after operation; the AOFAS ankle-hindfoot score was improved from (66.1±11.8)points before operation to (84.8±9.5)points at 3 months after operation and (92.9±8.6)points at 1 year after operation; the ankle ROM was improved from (48.5±7.5)° before operation to (61.9±10.3)° at 3 months after operation and (65.4±11.8)° at 1 year after operation (all P<0.05). There was no significant difference in VAS at 3 months and 1 year after operation ( P>0.05). There were significant differences in AOFAS ankle-hindfoot score and ankle ROM at 3 months and 1 year after operation (all P<0.05). According to AOFAS ankle-hindfoot score, the results were excellent in 11 patients, good in one, and fair in one, with the excellent and good rate of 92%. The MOCART score was 40-85 points [(70.4±14.2)points] at 1 year after operation. There was no postoperative necrosis, infection or neurovascular injury. Two patients had slight transient pain during rehabilitation training and were improved after non-surgical treatment. Conclusion:For posterior OLT, posterior ankle arthroscopic microfracture with PRP injection can effectively alleviate pain, improve ankle function and repair cartilage damage, with satisfactory short-term efficacy.