Guided by the theory of "fire and original qi are restricted"， it is believed that original qi depletion is the root of the cutaneous immune-related adverse events （cirAEs） related to immune checkpoint inhibitors （ICIs）， and the yin fire exuberance is the branch. Among them， original qi depletion is the internal foundation of the disease， while the drug toxicity of ICIs harming original qi is the initiating factor， and exuberant yin fire is the key pathogenesis. In clinical practice， the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction （补中益气汤） can be used to activate transportation of middle jiao （焦） and promote ascent and dispersion of clear yang， thereby restoring the balance of qi and fire， and medicinals such as Huangqin （Radix Scutellariae）， Huanglian （Rhizoma Coptidis） and Huangbai （Cortex Phellodendri Chinensis） can be supplementetd to clear and drain yin fire. At the same time， considering the accompanying symptoms such as dampness-stasis and fluids depletion， the methods of removing dampness and dispelling stasis， supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.

Objective:To compare the clinical efficacy of axillary transthoracic approach and posterior approach in the treatment of upper thoracic tuberculosis with vertebral clearance, bone graft fusion, and internal fixation surgery.Methods:Fifty five patients with upper thoracic tuberculosis admitted to Changsha Central Hospital, University of South China from March 2017 to March 2022 were selected and divided into axillary transthoracic group and posterior group according to different surgical approaches. The incision length, surgical time, intraoperative blood loss, and postoperative hospitalization time were compared between the two groups of patients. Two groups of patients were recorded for preoperative and postoperative pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores at 1 week, 3 months, and 12 months, preoperative and postoperative serum inflammatory indicators, CD4 + /CD8 + ratio of T lymphocyte subsets, and complications. Results:The incision length, operation time, and intraoperative blood loss in the axillary transthoracic group were significantly less than those in the posterior group, and the differences were statistically significant (all P<0.05). However, there was no statistically significant difference in postoperative hospitalization time between the two groups of patients ( P>0.05). The VAS and ODI scores of the two groups of patients showed significant improvement compared to preoperative levels at 1 week, 3 months, and 12 months after surgery (all P<0.05); And at 1 week and 3 months after surgery, the VAS scores of patients in the axillary transthoracic group were significantly lower than those in the posterior group (all P<0.05), and the ODI scores at 3 and 12 months after surgery were significantly lower than those in the posterior group (all P<0.05). The erythrocyte sedimentation rate and CRP levels of both groups of patients increased significantly one week after surgery compared with preoperative levels (all P<0.05), but the erythrocyte sedimentation rate and CRP levels basically returned to normal levels at three months after surgery. The CD4 + /CD8 + ratio of T lymphocyte subsets in both groups was lower than preoperative levels at one week after surgery, but with the continuation of treatment, the CD4 + /CD8 + ratio increased significantly at three months after surgery. Conclusions:Both axillary and posterior approaches can be used for surgical treatment of upper thoracic tuberculosis, but axillary and thoracic approaches have the advantages of less trauma, less bleeding, and faster recovery.

Objective To reduce the risk of cervical spinal cord injury,the most medial point of the cervical intervertebral disc that the posterior percutaneous endoscopic sheath could reach was evaluated.And that could help to determine the indication of posterior percutaneous endoscopic cervical discectomy for cervical intervertebral disc herniation.Methods Cervical MRI images for 50 randomly selected patients,21 males and 29 females with ages from 20 to 60(average 33.5± 10.03 years),were analysed.All 50 patients underwent MRI examination at our institution between January 2014 and December 2017.As 50％ of the zygapophyseal joint was preserved,on the cross-section T2-weighted MRI images,when the sheath just touched the spinal cord,the intersection point of the medial wall of sheath and cervical spinal cord (Point L) was the most medial point of the posterior percutaneous endoscopy could get.The distance between Point L and the line through and tangent to the most lateral point of cervical disc border was the length of the line section DL.The distance between the middle sagittal line of the cervical disc and the line through and tangent to the most lateral point of cervical disc border was the length of the line section D.D1/D was the most medial distance ratio of the posterior percutaneous endoscopic cervical discectomy when 50％ of the lateral zygapophyseal joint was preserved.In the same way,D'1/D was the most medial distance ratio of the posterior percutaneous endoscopic cervical discectomy when 75％ of the lateral zygapophyseal joint was preserved.Results When 50％ of the lateral zygapophyseal joint was preserved,the upper limit of 95％ confidence intervals of the most medial distance ratio that the posterior percutaneous endoscopy could get were 78％,76％,81％,93％ in C3,4,C4,5,C5,6,C6,7 respectively.This meant that the most medial distance the posterior percutaneous endoscopy could get were the 78％,76％,81％,0.93％ of the length of the line section D in C3,4,C4,5,C5,6,C6,7 respectively.The most medial distance the posterior percutaneous endoscopy could get in C5,6 or C6,7 was longer than that in C3,4,C4,5.Conclusion When 50％ of the lateral zygapophyseal joint was preserved,the upper limit of the most medial distance ratio that the posterior percutaneous endoscopy should get were 78％,76％,81％,93％ in C3,4,C4,5,C5,6,C6,7 respectively.This meant that the most medial distance the posterior percutaneous endoscopy could get were the 78％,76％,81％,93％ of the length of line section D in C3,4,C4,5,C5,6,C6,7 respectively.If the resected disc was beyond this range,the cervical spinal cord should be in the risk of being injured.

Objective To investigate the clinical efficacy and complications of minimally invasive transforaminal lumbar-interbody fusion (TLIF) in the treatment of lumbar spondylolisthesis. Methods Total 142 patients with single level spondylolis-thesis who treated by TLIF from 2010.01 to 2015.06 were included in this study, with 68 cases in minimally invasive TLIF (MIS-TLIF) group and 74 cases in traditional open TLIF group. The general information (age, gender, isthmic or degenerative type, per-centage of slip degree, levels), operative time, blood loss, length of postoperative hospital stay, Visual Analogue Scale (VAS) of low-back pain and leg pain, and Oswestry Disability Index (ODI) were recorded and collected. The posterior height of the interverte-bralpace and segmental lordosis, reduction of spondylolisthesis and cross-sectional area of spinal canal were measured. Results There was no statistically significant difference between the two groups in age, gender ratio, percentage of slip degree, and sur-gicallevels distribution. Total of 66 cases in MIS-TLIF group and 71 cases in Open TLIF group finished 2 years follow up, and 25 cases in MIS-TLIF group and 31 cases in Open TLIF group finished 5 years follow up. The blood loss of the MIS-TLIF group was 164.7±51.7 ml, significantly lower than the open TLIF group of 239±69.3 ml(P<0.001). The length of postoperative hospital stay was 5.9 ± 1.5 days in MIS-TLIF group, significantly shorter than the open TLIF group of 7.3 ± 3.1 days(P<0.001). The operative time of MIS-TLIF and Open TLIF was 146.3±21.9 mins, 152.0±20.4 mins, respectively, and no significant differ-ence was found between them. The VAS ofback pain, leg pain, ODI in MIS-TLIF group was 1.76±1.16, 1.91±1.36 and 23.5± 7.3 at 2 years follow up, and in Open TLIF was 1.73±1.10, 1.83±1.36 and 23.8±6.7, respectively, all of them were significant-ly different to pre-operation, however, no significant difference was found between two groups. The VAS of back pain, leg pain, ODI in MIS-TLIF group was 1.73±1.21, 1.93±1.48, and 25.4±6.8 at 5years follow up, and in Open TLIF was 1.85±1.02, 1.85± 1.33 and 26.1 ± 6.5, respectively, no significant difference between twogroups. The posterior height of the intervertebral space and segmental lordosis of MIS-TLIF was 9.52±1.67 mm and 12.11°±3.44° at 2 years follow up, while the open TLIF was 9.88± 1.54 mm and 12.98 ± 3.83° , all of them were significantly different to pre-operation,however, no significant difference between two groups. The posterior height of the intervertebral space and segmental lordosis of MIS-TLIF was 9.37 ± 1.46 mm and 11.55° ± 2.77° , while the open TLIF was 9.66 ± 1.68 mm and 12.59° ± 4.23° , no significant difference between two groups. The percentage of slip degree was reduced to 5.2％±4.6％ in MIS-TLIF and 5.6％±4.3％ in open TLIF, the cross-sectional area of spinal canal was enlarged to 139.7±19.5 mm2 and 141.7±20.7 mm2, no significant difference between two groups either. Con-clusion MIS-TLIF has less blood loss, shorter postoperative hospital stay than open TLIF, and similar clinical pain and function-al outcomes. MIS-TLIF is suggested to be a safe and effective choice in the treatment of lower grade lumbar spondylolisthesis (Grade II or less).

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.

Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.

Objective To examine the effect of metformin on serum thyrotropin (TSH) level in diabetic patients with subclinical hypothyroidism (SCH).Methods The long-term effects of metformin on thyroid axis hormones were assessed in 55 diabetic patients with primary SCH who were untreated with L-T4(study group),as well as in 31 diabetic patients with normal thyroid function (control group).According to using metformin or not,patients of study group were divided into the metformin group (group 1,n =28),and the non-metformin group(group 2,n =27).Serum TSH levels were compared between baseline and follow-up in patients receiving metformin treatment.Results After 30 weeks of metformin administration,a significant TSH decrease(t =2.91,P ＜ 0.05) was observed in group 1 [from(6.98 ± 1.92) to(2.44 ± 0.61) mIU/L].After stopping metformin therapy,the level of TSH at 52 weeks fol low-up was back to the baseline level [(6.99 ± 1.76) mIU/L,P ＞ 0.05].There was no significant difference in TSH level between baseline and after 30 weeks follow-up in group 2[(6.01 ± 1.63) mIU/L vs(6.21 ± 1.71) mIU/L,P ＞0.05].At the end of 30 weeks follow-up,no significant differences were found in body mass index and thyroid func tion in both metformin group and non-metformin group.In control group,metformin administration for 30 weeks had no effect on TSH level(P ＞ 0.05).Conclusion Metformin administration influences TSH without change of FT4 level in type 2 diabetic patients with primary SCH.

Objective To investigate complications associated with Coflex interspinous process device for degenerative lumbar disc diseases and methods to treat.Methods Clinical data of 121 patients with degenerative lumbar disc diseases,who had undergone surgical decompression and additional fixation of Coflex between November 2007 and June 2011,was analyzed retrospectively.There were 76 males and 45 females,aged from 37 to 75 years (average,54.6 years).Surgery-related complications and sequelae were recorded and analyzed.Results Surgery-related complications occurred in 10 patients,and the incidence was 8.3％ (10/121).There were 3 cases of device-related complications,including wing break in 1 case,prosthetic loosening in 1 case and spinal process fracture in 1 case; all 3 cases were treated conservatively and received good results.There were 7 cases of non-device-related complications,including dura mater dilaceration in 2 cases,superficial wound infection in 1 case,insufficient decompression of spinal canal in 2 cases,recurrence of disc herniation in 1 case,and intraspinal hematoma in 1 case; the former 3 patients recovered after corresponding treatment,and the latter 4 patients also recovered after re-operation.Conclusion The incidences of complications and re-operation associated with application of Coflex are low,and the incidence of device-related complications is also low.The precise intraoperative manipulation is the key to reduce incidence of device-related complications.It's absolutely necessary to strictly master surgical indications and perform sufficient decompression in order to receive good surgical results and avoid non-device-related complications.

Objective To evaluate the mid-term clinical effects and the imaging changes of Coflex interspinous dynamic internal fixation for low back pain. Methods From February 2007 to June 2009,Coflex interspinous dynamic internal fixation was performed in a consecutive 45 patients. They included 26 males and 19 females, with an average of 51.4 years ranging in age from 45 to 70 years. Thirty-two cases were in L4.5 level, 11 in L5S1 level and 2 in both two levels. The patients were treated with limited laminectomy and implanted with Coflex device. Clinical outcomes were assessed by Oswestry disability index (ODI)scores and Japanese Orthopaedic Association (JOA) questionnaires before and after operation. The imaging examination was obtained to assess height of the intervertebral space, area of the intervertebral foramen,segment movement of the operation level, low lumbar curvature and signal of the lumbar disc on MRI. Results The follow-up time ranged from 10 to 34 months, with an average of 24 months. The ODI scores decreased significantly from 62.82±10.42 preoperatively to 11.80±3.35 postoperatively. The JOA scores were improved remarkably from 9.00±2.63 preoperatively to 24.65±1.86 postoperatively. The proportion with optimal effect was 89% (40 cases). The Cobb angle after operation of L4.5 and L5S1 level was 15.1°±3.9° and 16.3°±3.8° respectively, which was significantly decreased after operation. The range of motion of the L4.5 level increased from 6.5°±1.5° to 8.4°±2.6° while the L5S1 level did not change notedly. The heights of the dorsal intervertebral disc, distance of the spinous processes, intervertebral foramen height and area were significantly higher than those before operation. Conclusion The Coflex interspinous dynamic internal fixation is available to reserve segment movement, to increase intervertebral space height and foramen area. Meanwhile,it is effective to self-repair and prevent degeneration for the disc in adjacent levels.

Objective To discuss the clinical characteristics and treatment of upper cervical spine injuries in the elderly. Methods A retrospective study was done on clinical data of 28 elderly patients ( > 60 years old) with upper cervical spine injuries treated from January 2003 to December 2007. There were 20 males and 8 females, at age range of 60-86 years (mean 68.1 years). Injury causes included slip in 16 patients, traffic injury in eight and fall from height in four. Atlas fractures occurred in five patients and axis ones in 15,of which there were eight patients with odontoid fractures, six with C2 vertebral arch fractures and one with C2 body fractures. Upper cervical spine injury was combined with lower cervical spine injuries in five patients. There were combined atlantoaxial injuries including odontoid fractures combined with lateral atlas fracture in one and edontoid fractures combined with anterior atlas arch fracture in one. Atlantoaxial dislocation occurred in one patient and combined spinal injury in four. Of all, eight patients were treated conservatively, eight with open surgical operation and 12 with minimally invasive surgery. Results The average hospital stay was 16.5 days, with no statistical difference be-tween conservative treatment group and open surgical operation group ( P > 0.05 ). While the average hos-pital stay in minimally invasive surgery group was shorter than that in conservative treatment and open sur-gical operation groups ( P < 0.05 ). Of all, two patients in conservative treatment group and one in open surgical operation group died and the other 25 patients were followed up for average 16.8 months (9-56 months). The satisfaction rate was 50% in conservative treatment group, 72% in open surgical operation group and 75% in minimally invasive surgery group. Complications occurred in four patients in conserva-tive treatment group, three in open surgical operation group and two in minimally invasive surgery group. Conclusions With odontoid fracture the most common injury type, upper cervical spine injuries arema-inly caused by low-energy force and characterized by low mobidity of spinal cord injuries and high possi-bility of missed diagnosis in the elderly patients. The surgical treatment especially minimally invasive surgery can bring good results compared with conservative methods.