1.Discussion on the Pathogenesis and Treatment of Knee Osteoarthritis from the Theory of"Deficient Qi Stagnation"Based on Mitophagy
Zifeng YE ; Gaoyan KUANG ; Yiwei YUAN ; Liguo QIU ; Xiaotong XU ; Zhi WEN ; Min LU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):14-18
Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.
2.Multi-center Study on Specific IgE Antibodies to Alternaria Alternata and Aspergillus Fumigatus in Sera of Clinical Allergy Patients in Selected Provinces in China
Chao XU ; Xingyuan ZHU ; Caizhi HUANG ; Hong ZHU ; Shu WANG ; Hongxia YUAN ; Pengfei ZHAO ; Ji YAN ; Jianhua MA ; Chunlei KUANG ; Yanli XIE ; Rongcai WU ; Yu ZHANG ; Sheng LIANG ; Qunying WANG ; Yingsha DUAN ; Yiwu ZHENG
Journal of Modern Laboratory Medicine 2025;40(3):13-17
Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.
3.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
4.Multi-center Study on Specific IgE Antibodies to Alternaria Alternata and Aspergillus Fumigatus in Sera of Clinical Allergy Patients in Selected Provinces in China
Chao XU ; Xingyuan ZHU ; Caizhi HUANG ; Hong ZHU ; Shu WANG ; Hongxia YUAN ; Pengfei ZHAO ; Ji YAN ; Jianhua MA ; Chunlei KUANG ; Yanli XIE ; Rongcai WU ; Yu ZHANG ; Sheng LIANG ; Qunying WANG ; Yingsha DUAN ; Yiwu ZHENG
Journal of Modern Laboratory Medicine 2025;40(3):13-17
Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.
5.Discussion on the Pathogenesis and Treatment of Knee Osteoarthritis from the Theory of"Deficient Qi Stagnation"Based on Mitophagy
Zifeng YE ; Gaoyan KUANG ; Yiwei YUAN ; Liguo QIU ; Xiaotong XU ; Zhi WEN ; Min LU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):14-18
Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.
6.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
7.Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients
Jian′ang LI ; Yaolin XU ; Ni DING ; Yuan JI ; Lingxiao LIU ; Shengxiang RAO ; Yiqun ZHANG ; Xiuzhong YAO ; Yue FAN ; Cheng HUANG ; Yuhong ZHOU ; Lili WU ; Yi DONG ; Lei ZHANG ; Yefei RONG ; Tiantao KUANG ; Xuefeng XU ; Liang LIU ; Dansong WANG ; Dayong JIN ; Wenhui LOU ; Wenchuan WU
Chinese Journal of Surgery 2022;60(7):666-673
Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.
8.Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients
Jian′ang LI ; Yaolin XU ; Ni DING ; Yuan JI ; Lingxiao LIU ; Shengxiang RAO ; Yiqun ZHANG ; Xiuzhong YAO ; Yue FAN ; Cheng HUANG ; Yuhong ZHOU ; Lili WU ; Yi DONG ; Lei ZHANG ; Yefei RONG ; Tiantao KUANG ; Xuefeng XU ; Liang LIU ; Dansong WANG ; Dayong JIN ; Wenhui LOU ; Wenchuan WU
Chinese Journal of Surgery 2022;60(7):666-673
Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.
9.Jujuboside A ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway.
Yang-Yang LIU ; Lin LI ; Bei JI ; Shi-Long HAO ; Xiao-Feng KUANG ; Xin-Yun CAO ; Jia-Yu YUAN ; Zhen-Zhou JIANG ; Si-Tong QIAN ; Chu-Jing WEI ; Jing XU ; Xiao-Xing YIN ; Qian LU ; Ting-Ting YANG
Chinese Journal of Natural Medicines (English Ed.) 2022;20(9):656-668
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg-1·d-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals
;
Blood Glucose
;
Diabetes Mellitus, Experimental/metabolism*
;
Diabetes Mellitus, Type 2/drug therapy*
;
Diabetic Nephropathies/metabolism*
;
Fibrosis
;
Mice
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Saponins
;
Signal Transduction
;
Streptozocin
;
Transforming Growth Factor beta1/metabolism*
10.Complications and management of penile augmentation with hyaluronic acid injection.
Yuan QUAN ; Zi-Rui GAO ; Xiang DAI ; Ling KUANG ; Min ZHANG ; Qing LI ; Tao XU ; Xiao-Wei ZHANG
Asian Journal of Andrology 2021;23(4):392-395
Hyaluronic acid injection is becoming a popular way for penile augmentation. However, only few studies and follow-ups have investigated the various complications of hyaluronic acid injection and their corresponding management. In this study, a total of 230 patients who had penile augmentation with hyaluronic acid injection from January 2018 to December 2019 were examined on follow-up for penile girth, complications, and their corresponding management. At 1-month, 3-month, and 6-month postoperative follow-ups, the penile circumference had increased by 2.66 ± 1.24 cm, 2.28 ± 1.02 cm, and 1.80 ± 0.83 cm, respectively. During the entire 6-month follow-up, 4.3% had complications such as subcutaneous bleeding, subcutaneous nodules, and infection. There were no systemic or local allergic reactions among all the patients. All complications were treated accordingly, and no further deterioration or severe sequelae were observed. Although complications of hyaluronic acid injections are mild and rare, these may affect the patient's satisfaction postoperatively. Preoperative redundant prepuce may increase the incidence of penile edema or postoperative gel migration. Standardization of the surgery protocol and elucidation of the effects of other injection parameters are still lacking. Nevertheless, it still highlights the importance of preoperative preparation and surgical technique.

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