Knee osteoarthritis（KOA）is one of the most commonfrequent chronic diseases today，and it has a significant impact on a patient′s physical，mental，and social well ⁃being. Treatment combining Traditional Chinese Medication（TCM）and western medicine has undeniably proven to be beneficial in the overall manage⁃ ment of KOA. The KOA instruction in TCM and western medicine clinical practice is extremely important，as it was written on the basis of Evidence⁃based Medicine. It aids in the standardization and improvement of diagnostic and treatment practices in both Chinese and Western medicine. The instruction was created in accordance with the clinical practice guideline′ s standards.It excludes standards such as range，words，definitions，epidemic characteristics， diagnosis，treatment，effect evaluation，and other components of the KOA diagnostic and treatment process in TCM and western medicine.The instruction was created in accordance with the clinical practice guideline′ s stan⁃ dards. It excludes standards such as range，words，definitions，epidemic characteristics，diagnosis，treatment， effect evaluation，and other components of the KOA diagnostic and treatment process in TCM and western medicine. In terms of disease differentiation and syndrome differentiation of TCM，this instruction highlights the influence of territorial characteristic on KOA occurrence，development，and distribution of different syndrome types in TCM. With regards to the aspect of treatment，the instruction highlights the exercise and training′ s importance on the whole KOA treatment management. More than that，the instruction provides recommendation on the exercise/train⁃ ing way，method，movement detail，intensity and treatment course. Besides，some techniques applied in non⁃oper⁃ ative KOA treatment are underscored in this instruction，such as acupuncture，small needle⁃knife，acupoint injec⁃ tion，and so on. This training adapts well to clinical practice and is both safe and effective.

Objective To investigate the clinical characteristics and laboratory results of patients infected with the Delta variant of concern（VOC）vs a cohort of wild⁃type. Methods A total of 145 patients infected with Delta VOC in Guangzhou Eighth People′s Hospital Affiliated to Guangzhou Medical University from May to June， 2021 were retrospectively analyzed as a contrast of 278 patients infected with wild ⁃type strain from January to February，2020. The differences of general demographics，clinical symptoms，laboratory examinations，lung CT imaging results were analyzed. Results In the Delta VOC group，common type was majority and 13 patients（11%） were severe and critical types. In terms of time interval from early onset to severe manifestation，patients in the Delta VOC group were significantly shorter than that of the wild⁃type strain group（P ≤ 0.05）. The incidences of pharyngodynia and anosmia in the Delta VOC group were significantly greater than those in the wild ⁃type strain group（P ≤ 0.05）. The incidences of the lymphocyte count decline in the Delta VOC group were significantly greater than those in the wild⁃type strain group（P ≤ 0.05）. The first time CT mainly showed that the ground glass opacity and interstitial inflammation change in the Delta VOC group showed no significant difference compared with the wild⁃type group（all P > 0.05）. Conclusion Mild case was still the primary type for patients infected with Delta VOC，the rate of severe cases didn′t increase apparently，but the time interval from onset to severe manifestation was significantly lower than that of the wild⁃type strain group. There was little difference between the two groups on multiple organs or systems injury.

Objective To obtain the 58 amino acid peptide of the carboxyl terminal of ETAR（ETAR ⁃ C58）and investigate the effects on the migration and invasion of melanoma A375 cells. Methods ETAR ⁃C58 sequence was amplified by PCR，inserted into the vector pWaldo⁃GFPe and then transformed into Escherichia coli BL21（DE3）. After expression，the fusion peptide was purified by nickel column affinity chromatography and gel filtration chromatography，analyzed by SDS ⁃PAGE and further identified by immunoblotting. Finally，Transwell assay was carried out to measure the migration and invasion of A375cells. Results The recombinant expression vector pWaldo⁃ETAR⁃C58 was successfully constructed and the soluble fusion peptide was accounted for approxi⁃ mately 90%. SDS⁃PAGE and immunoblotting results verified the successful purification of the ETAR⁃C58 with nearly 95% purity. ETAR ⁃ C58 peptide could inhibit A375 cell migration and invasion at 2 μmol/L. Conclusion The ETAR⁃C58 peptide have anti⁃melanoma activity，which allows a possibility for further clinical application.

Objective To investigate the effect and mechanism of STAT3/SDF⁃1 signaling pathway of spinal dorsal horn neurons in postoperative chronic pain. Methods A SMIR animal model，with or without antiSDF ⁃1 and S3I⁃201 intrathecally，was established. Mechanical withdrawal threshold on the ipsilateral side before and after operation，expression level of SDF⁃1 and STAT3，and cell location in the spinal dorsal horn were observed. In addition，ChIP was used to detect the interaction between STAT3 and SDF⁃1 promoter. Results The mechanical withdrawal threshold of rats on the 5th，10th，and 20th day after operation was significantly reduced，accompanied by up⁃regulation of the expression of SDF⁃1 and p⁃STAT3 in the spinal dorsal horn neurons，and all co⁃stained with Neun⁃positive neurons. AntiSDF⁃1 and S3I⁃201 pretreatment alleviated the changes in the mechanical withdrawal threshold after SMIR，and S3I ⁃201 also reduced the upregulation of SDF ⁃1 transcription and translation after surgery. After SMIR，the combination of STAT3 and SDF⁃1 promoter in the dorsal horn of the spinal cord was in⁃ creased. Conclusions STAT3/SDF⁃1 signaling pathway of spinal dorsal horn neurons is involved in the formation of postsurgical chronic pain.

Objective To study the effect and mechanism of namefen hydrochloride combined with electri⁃ cal vagal stimulation on lung ischemia⁃reperfusion injury. Methods A total of 75 rats were randomly divided into model group，electrical vagal stimulation group，nalmefene group，nalmefene combined with electrical vagal stimu⁃ lation group and sham operation group equally（n = 15）. The lung ischemia⁃reperfusion model was established by occlusion of the left pulmonary hilum in the model group. When the lung tissue expanded and the color recovered based on lung ischemia⁃reperfusion model，left vagus nerve was stimulated and namefen（15 μg/kg）was injected into the tail vein immediately in electrical vagal stimulation group and in the namefen group respectively. When the lung tissue expanded and the color recovered based on lung ischemia⁃reperfusion model，left vagus nerve stimula⁃ tion and namefen（15 μg/kg）injected into the tail vein were synchronously applied in nalmefene combined with electrical vagal stimulation group. The sham operation group without occlusion of the left pulmonary hilum was not given any treatment. At 3 h after reperfusion，all rats were detected arterial blood gas value and then sacrificed. The specimens from the upper lobe of the left lung tissue were preserved to observe pulmonary lesions ，detect the ratio of wet/dry weight and the expressions of myeloperoxidase，dynorphin，κ ⁃receptor and IL⁃17 in lung tissue. Results Compared with those in the model group，the value of pCO2，the degree of pulmonary lesions，the ratio of wet/dry weight and the expressions of myeloperoxidase and IL⁃17 in lung tissue were significantly decreased（P < 0.01），and the value of pO2 was significantly increased（P < 0.01）in the electrical vagal stimulation group and the nalmefene group. The expression of dynorphin and κ⁃receptor in lung tissue were significantly decreased in the nalmefene group（P < 0.01），but this expression was not significantly changed in the electrical vagal stimulation group（P > 0.05）. Compared with those in electrical vagal stimulation group，the value of pCO2，pO2，the degree of pulmonary lesions，the ratio of wet / dry weight and the expressions of myeloperoxidase and IL ⁃ 17 in lung tissue were not significantly changed（P > 0.05），but the expression of dynorphin and κ ⁃receptor were significantly decreased in the nalmefene group（P < 0.01）. Compared with those in the nalmefene group or the electrical vagal stimulation group，the value of pCO2，the degree of pulmonary lesions，the ratio of wet/dry weight and the expres⁃ sions of myeloperoxidase，dynorphin，κ⁃receptor and and IL⁃17 in lung tissue were significantly decreased（P < 0.01），and the value of pO2 was significantly increased in the nalmefene combined with electrical vagal stimulation group（P < 0.01）. Conclusion Nalmefene may inhibit the lung ischemia ⁃ reperfusion injury by accelerating the degradation of dynorphin and alleviating the inflammatory reaction of lung tissue. Electric stimulation of vagus nerve attenuates pulmonary ischemia⁃reperfusion injury by inhibiting inflammatory response. The treatment of nalmefene combined with electrical vagal stimulation in the prevention and treatment of lung ischemia⁃reperfusion injury may produce synergistic effects.

Objective To investigate the effect of liraglutide combined with zinc alpha2 glycoprotein （ZAG）on palmitic acid⁃induced HepG2 cell apoptosis，lipid metabolism and the expression of inflammatory factor. Methods Real⁃time quantitative PCR（RT⁃qPCR）and western blotting were used to analyze the expression levels of ZAG in liver tissues of patients with non⁃alcoholic fatty liver disease（NALFD）and palmitic acid⁃induced HepG2 cells. HepG2 cells were divided into control group，palmitic acid group，palmitic acid + liraglutide group，palmitic acid + pcDNA⁃ZAG group，palmitic acid + liraglutide + ZAG shRNA group，palmitic acid + liraglutide + pcDNA⁃ ZAG group. Cell apoptosis was detected by flow cytometry. Kit was applied to determine the levels of total cholesterol （TC）and triglycerides（TG）in the cells，as well as the levels of interleukin 6（IL⁃6）and tumor necrosis factor⁃α （TNF⁃α）in the supernatant of the cell culture medium. Results The expression of ZAG mRNA and ZAG protein in liver tissues of NALFD patients was significantly reduced（P < 0.05）. Treatment with Palmitic acid significantly down⁃regulated the expression of ZAG mRNA and ZAG protein，increased the levels of TC，TG，IL⁃6 and TNF⁃α， and increased the apoptosis rate of HepG2 cells（P < 0.05）. Treatment with liraglutide or over⁃expression of pcDNA⁃ ZAG significantly inhibited palmitic acid⁃induced apoptosis of HepG2 cells，and reduced the levels of TC，TG，IL⁃6 and TNF ⁃α（P < 0.05）. Silencing ZAG significantly weakened the effect of liraglutide on palmitic acid ⁃induced apoptosis，TC，TG，IL ⁃6 and TNF ⁃ α levels in HepG2 cells（P < 0.05）. Over ⁃ expression of ZAG significantly enhanced the effect of liraglutide on palmitic acid⁃induced apoptosis，TC，TG，IL⁃6 and TNF⁃α levels in HepG2 cells（P < 0.05）. Conclusion Liraglutide combined with ZAG can inhibit palmitic acid⁃induced apoptosis，lipid deposition and inflammatory reaction in HepG2 cells. 

Objective To study the relationship between immune activation and host restriction factor SAMHD1expression and HIV ⁃1 DNA levels in HIV ⁃1 infected patients. Methods A total of 57 HIV ⁃1 patients without antiretroviral therapy（ART），62 HIV⁃1 patients with ART and 48 healthy controls were recruited. Periph⁃ eral blood mononuclear cells（PBMCs）and CD4 + T cells were purified. SAMHD1 mRNA and HIV⁃1 RNA were detected by RT⁃PCR. Count of CD4 + and CD8 + T cells，and immune activation of CD4 + T cells were analyzed by flow cytometry. HIV⁃1 DNA levels in peripheral blood were detected by PCR. Results Immune activation of CD4+ T cells was increased in HIV⁃1 patients，especially in ART naïve group. HIV⁃1 DNA levels in peripheral blood of ART naïve patients were much higher than those of the patients in ART group（P < 0.01）. We found elevated SAM⁃ HD1 mRNA levels in PBMCs of all HIV ⁃1 patients，but decreased levels in CD4 + T cells compared with healthy controls（P < 0.01）. SAMHD1 expression was inversely associated with immune activation. No relationship was found between SAMHD1 and HIV⁃1 DNA levels. Conclusion SAMHD1expression in CD4+ T cells was decreased in HIV ⁃1 patients and negatively related to immune activation levels. No direct relationship found between SAM⁃ HD1 expression and HIV⁃1 DNA levels.

Objective To investigate the relation of multiple single nucleotide polymorphisms（SNPs）of vitamin D receptor gene with gestational diabetes mellitus，in order touncover genetic susceptibility factors and pro⁃ vide a foundation for GDM prevention and treatment. Methods According to inclusion criteria，555 pregnant wom⁃ en diagnosed with GDM during 24 ~ 28 weeks were assigned to the case group，while 646 healthy pregnant women were assigned to the control group. Fluorescence quantitative PCR was used to genotype the VDR gene polymor⁃ phisms rs2228570 and rs739837.To investigate the relationship between polymorphisms in the VDR gene and GDM risk，multivariate logistic regression models were used. Results The frequency of GA genotype of rs2228570 in GDM group（52.43%）was higher than that in control group（50.77%），individuals with the GA genotype had a 2.80⁃ fold increased risk of developing GDM（OR = 2.80，95%CI：1.06 ~ 7.40，P = 0.038）；The frequency of AA geno⁃ type in GDM group（29.01%）was significantly higher than that in control group（24.15%），individuals with the AA genotype had a 3.98⁃fold increased risk of developing GDM（OR = 3.98，95%CI：1.23 ~ 12.86，P = 0.021）. The frequency of A allele of rs2228570 in GDM group was significantly higher than that in control group（55.23% vs. 49.54%，OR = 1.72，95%CI：1.04 ~ 2.85，P = 0.035）. The rs2228570 were associated with GDM in a dominant model （OR = 3.07，95%CI：1.20 ~ 7.86，P = 0.019）. There were no statistically significant differences in genotypes and allele frequency distribution of rs739837 between the case and control groups（P > 0.05）. Multivariate logistic regres⁃ sion analysis showed that family history of diabetes and rs2228570 polymorphism were independent risk factors for GDM（P＜0.05）. Conclusions The rs2228570 loci of VDR gene is associated with the pathogenesis of GDM， indicating that the vitamin D receptor gene might be one of the susceptibility genes to GDM in the Chinese population.

Objective To explore the expression of follicle⁃like 3（FSTL3）gene in colon cancer and its influence on the prognosis. Methods The expression of FSTL3 was detected and the clinical prognosis through the TCGA database was analyzed. The expression level of FSTL3 in colon cancer cases was detected by immuno⁃ histochemical analysis，and the relationship between its expression and the clinicopathological characteristics and prognosis was analyzed. SW620 cells were selected，cell lines with overexpression and silence of FSTL3 gene were constructed，respectively，and the transfection efficiency was detected by Western blot. MTT，clone formation test， and Transwell test were used to detect changes in proliferation and migration capabilities. Results The expression of FSTL3 in the TCGA database was significantly increased，and clinical survival analysis showed the prognosis of patients with high FSTL3 expression was significantly worse than that of patients with low FSTL3 expression（P < 0.008）. By using ROC，the evaluationof the diagnostic efficacy of FSTL3 for colon cancer was more accurate. In clinical cases，the FSTL3 gene was highly expressed（P < 0.001）. The expression of FSTL3 in colon cancer was related to age（0.049），TNM stage（P = 0.033），depth of invasion（P = 0.06），distant metastasis（P = 0.001）， and is related to gender（P = 0.386），lymphatic metastasis（P = 0.215），the degree of differentiation（P = 0.565） is irrelevant. And in colon cancer tissues，the survival rate of patients with high expression of FSTL3 was signifi⁃ cantly lower than that of patients with low expression（P < 0.008）. MTT experiments and clone formation experi⁃ ments confirmed that in SW620 cells，overexpression of FSTL3 enhanced cell proliferation，while knocking down FSTL3 decreased cell proliferation （P < 0.05）. Transwell experiments showed that overexpression of FSTL3 enhanced the migration ability of cells（P < 0.05），and knockdown of FSTL3 inhibited the migration ability of SW620 cells（P < 0.05）. Conclusion FSTL3 is highly expressed in colon cancer and is closely related to the prognosis of patients. The expression of Shen FSTL3 inhibits the proliferation and migration of colon cancer cells. FSTL3 may be considered as a molecular marker for predicting the development and prognosis of colon cancer.

Objective This study aims to explore whether the association between body mass index（BMI） and prognosis of estrogen receptor positive（ER+）breast cancer（BC）varies according to the tumor PR status. Methods We collected a total of 1 036 cases with invasive ductal breast cancer from March 2012 to January 2018 in department of breast surgery of Shanxi Bethune Hospital. Women were stratified according to their BMI（< 24， ≥ 24 kg/m2）. Tumor PR status（PR-，PR+）was evaluated by immunohistochemistry. The differences of clinico⁃ pathological features between the groups with different BMI levels were compared；Kaplan⁃Meier method was used to draw the overall survival（OS）curve of the whole group and the patients stratified by PR with different BMI levels，and log⁃rank test was performed. Univariate and multivariate Cox proportional hazards models were used to analyze the factors affecting OS. Results The median follow ⁃ up period was 4.0 years（2.3 ~ 5.7 years）. There were significant differences in age，histological grade，stage，menstrual status and family history of tumor between BMI < 24 kg/m2 group and BMI ≥ 24 kg/m2 group（P < 0.05）. In the whole group，OS in BMI <24 kg/m2 group was better than that in BMI ≥ 24 kg/m2 group（P = 0.033）. In breast cancer patients with PR ⁃ and ER+，OS in BMI < 24 kg/m2 group was better than that in BMI ≥ 24 kg/m2（P = 0.007）；In breast cancer patients with PR+ and ER+，there was no significant difference in OS between BMI < 24 kg/m2 group and BMI ≥ 24 kg/m2 group（P 0.466）. Univariate Cox regression analysis showed that BMI，PR，stage and menstrual status were associated with OS in ER positive breast cancer patients（P < 0.05）. Multivariate Cox regression analysis showed that BMI ≥ 24 kg/m2 （HR = 1.916，95% CI：1.167 ~ 3.144，P = 0.010）and PR negative（HR = 0.348，95% CI：0.208 ~ 0.583，P < 0.001） were independent risk factors for OS in ER positive breast cancer patients. Conclusion Compared with PR+，ER+ obese breast cancer patients，PR-，ER+ women had poorer survival. It suggests that poorer survival is associated with high BMI among women diagnosed with ER+ BC，which provides reference for the prevention and treatment of breast cancer.

Objective To compare the clinical effects of low⁃temperature plasma nucleoplasty with different number of puncture channels in the treatment of lumbar disc herniation. Methods 45 patients who had received low ⁃temperature plasma nucleoplasty patients were selected as research objects，and randomly divided into three groups（group 1 for 2⁃channel group，group 2 for 4⁃channel group，and group 3 for 6⁃channel group）. The VAS score，ODI lumbar dysfunction score，PPI pain intensity score，modified Macnab score，and degree of satisfaction were used for assessing the preoperative and postoperative pain level and the clinical efficacy. Results The surgical procedures were successfully performed in 45 patients and no adverse reactions occurred. As compared with the baselines，the VAS scores were significantly decreased in the three groups on postoperative day 1，week 1，and months 1 and 3（P < 0.01），but they declined more significantly in groups 2 and 3 than in group 1（F = 4.219， P < 0.01）；the ODI score was significantly decreased in the three groups（P < 0.01），and it was decreased more significantly in groups 2 and 3 than in group 1（F = 3.413，P < 0.01）；the PPI score was significantly decreased in the three groups（P < 0.05），and there were no significant differences in the degree of PPI decline among the three groups at each time point（F = 1.327，P = 0.233）；the modified MacNAB score and satisfaction degree were all higher in the three groups three months after surgery，and there were no significant differences（P > 0.05）. Conclusions Considering the postoperative pain relief and functional recovery of the lumbar spine，surgical com⁃ plexity and potential injury in patients receiving low⁃temperature plasma nucleoplasty，we suggest the four⁃channel surgical approach should be selected for the treatment of lower limb neuralgia caused by lumbar disc herniation. 

Objective To investigate the effects of natural orifice specimen extraction（NOSE）in laparo⁃ scopic colorectal cancer（CRC）surgery on bacterial contamination and dissemination of exfoliated tumor cells. Methods Eligible patients were randomly assigned to two groups：the traditional laparoscopic surgery group and the laparoscopic with NOSE group. Related indicators were compared. Results 92 patients were enrolled in the study. There were no significant differences in bacterial culture and the positive rate of free tumor cells in the perito⁃ neal lavage fluids at the beginning and the end of the surgery between the two groups，and the comparisons within each group were statistically significant（P < 0.05）. There was no significant difference in the positive rate of free tumor cells in the intestinal lavage fluids before and after anastomosis between the two groups and within each group. The follow⁃up time was 3 ~ 53 months. There were no significant differences between the two groups in the local relapse ⁃ free survival（LRFS），nodal relapse ⁃ free survival（NRFS），and distant metastasis ⁃ free survival （DMFS）. Conclusion Compared with traditional laparoscopic surgery，NOSE showed no significant differences in terms of bacterial contamination at the surgical area，exfoliation and implantation of tumor cells during surgery， and tumor recurrence and dissemination.

Objective To explore the risk factors related to No.253 lymph node metastasis，in order to provide reference for No.253 lymph node dissection. Methods The data of 205 patients with colorectal cancer who underwent radical resection in our department from September 2017 to April 2019 was retrospectively analyzed. The clinicopathological factors that may affect lymph node metastasis of No.253 were selected for risk factor analysis. Results Univariate analysis data showed that No.253 lymph node metastasis was significantly related to the distance from the tumor to the anal margin，preoperative serum CEA，preoperative serum CA19⁃9，T stage，vascular tumor thrombus and nerve invasion（P＜0.05）. Multivariate Logistic regression analysis results demonstrated that vascular tumor thrombus［OR＝8.506，95%CI（1.841，39.302）］was an independent risk factor for No.253 lymph node metastasis. Conclusion Vascular tumor thrombus is an independent risk factor for No.253 lymph node metas⁃ tasis. It could be an important reference factor for selective No.253 lymph node dissection.

Objective To explore the effect of preserved infrapatellar fat（IPFP）pad on the postoperative function and wound healing of patients undergoing artificial total knee arthroplasty. Methods A total of 150 patients with severe knee arthritis were randomly divided into IPFP resection group and IPFP preservation group. The follow up time was 1 month，2 months，3 months，6 months and 12 months after operation. There was no significant difference in gender，age，anterior knee pain，KSS knee function score and range of motion between the two groups before operation. Results All the 150 patients were included in the study. There was no difference between the two groups in the operation time，postoperative drainage volume and postoperative drainage time（P > 0.05）. The follow.up results showed that there was no difference in the KSS knee function score between the two groups at each time point after operation. However，the incidence of subincisional exudation in the IPFP resection group was significantly higher than that in the IPFP preservation group（13% vs. 6%，P < 0.05）. At 1，2 and 3 months after operation，the anterior knee pain level of the resection group was significantly higher than that of the preservation group（P < 0.05），but at the other two time points，there was no significant difference between the two groups. Conclusion The preservation of infrapatellar fat pad during total knee arthroplasty can increase the incidence of early postoperative wound exudation and early postoperative anterior knee pain. The infrapatellar fat pad should be preserved as much as possible or even reconstructed during the operation.

Objective To investigate the feasibility and safety of low⁃dose ticagrelor in acute coronary syn⁃ drome with percutaneous coronary intervention after 12months. Methods The acute coronary syndrome patients who underwent PCI in our hospital after 1 year from January 2017 to June 2019 were enrolled and randomly divided into three groups according to different antiplatelet strategies：Aspirin group（100 mg，once a day），Ticagrelor group（90mg twice daily）and Low⁃dose ticagrelor group（60 mg，twice daily）. At a follow⁃up of 24 months，the Major Adverse Cardiovascular Events（MACCE）and all bleeding events were compared among the three groups， and platelet aggregation rates were measured. Results During the follow⁃up，there was no statistical significance in the incidence of MACCE among 3 groups（P > 0.05）. Compared with the Aspirin group and Ticagrelor group， the Low⁃dose ticagrelor group had a decreasing trend of BARC1 hemorrhage，and the difference was statistically significant（P = 0.002）. There was no statistical significance in the risk of bleeding above BARC1 among the three groups（P > 0.05）. There was no statistical significance in platelet aggregation rate between 2 groups at each follow⁃ up time（P > 0.05）. Conclusions After 1year，in the selection of antiplatelet agents in acute coronary syndrome with PCI，low⁃dose ticagrelor can effectively reduce the incidence of bleeding events without affecting the antiplatelet aggregation effect.

Objective To study the analgesic effect of hydromorphone and oxycodone on PCIA after thora⁃ coscopic lung cancer surgery. Methods 144 patients with lung cancer were divided into three groups. 60 cases wereincluded in hydromorphone group，while 39 cases and 45 caseswererespectivelyincluded in oxycodone group and sufentanil group. PCIA was performed. NRS and adverse reactions at 3，6，12，24，36 and 48 hours were recorded. Results There was significant difference in NRS score among the three groups（P < 0.05）. Multiple comparisons：the analgesic effects of hydromorphone and oxycodone were statistically significant from sufentanil （P < 0.05），whilethere was no significant difference between hydromorphone and oxycodone（P > 0.05）. Adverse reactions：there was no significant difference at 3，6，24，36 and 48 hours（P > 0.05）；whilethere was significant difference in dizziness 12 hours after operation（P < 0.05）. Inmultiple comparisons，the incidence of dizziness between HM and SF was statistically significant（P = 0.010 < 0.0125，Chi ⁃ square partition）. Conclusion The multimodal analgesia of hydromorphone PCIA combined with TPVB and intravenous ketorolac tromethamine can provide comfortable treatment after lung cancer surgery.

Objective To analyze the clinical value of ulinastatin combined with bronchoalveolar lavage （BAL）in patients undergoing mechanical ventilation due to respiratory failure caused by pulmonary infection. Methods A total of 117 patients with respiratory failure caused by pulmonary infection who underwent mechanical ventilation in ICU of the First Affilicated Hospital of Zhengzhou University between January 2017 and June 2020 were divided into observation group（BAL combined with ulinastatin，n = 58）and control group（BAL，n = 59） according to treatment method. The levels of peripheral blood inflammatory factors，lung function indexes，blood gas indexes，adverse reactions and prognosis were compared between the two groups. Results After treatment，the levels of peripheral blood tumor necrosis factor α（TNF⁃α），transforming growth factor⁃β1（TGF⁃β1）and C⁃reactive protein（CRP）were reduced in the two groups，and the levels in observation group were lower than those in the control group（P < 0.05）. After treatment，tidal peak expiratory flow（PTEF），ratio of VPEF to peak tidal expiratory flow and total expiratory time（VPTEF/VTE），ratio of time to peak tidal expiratory flow and total expiratory time （TPTEF/TE），the 50% tidal volume during expiratory flow（TEF50%）/PTEF and the 25% tidal volume during expi⁃ ratory flow（TEF25%）/PTEF were increased in the two groups，and the above indexes in observation group were higher than those in the control group（P < 0.05）. After treatment，oxygenation index（OI）and partial pressure of arterial oxygen（PaO2）were increased，and arterial partial pressure of carbon dioxide（PaCO2）was reduced in the two groups. The observation group had higher OI and PaO2，and lower PaCO2 than the control group. There was no signifi⁃ cant difference in expectoration volume or 28 d mortality between the two groups（P > 0.05）. The observation group had shorter mechanical ventilation time and hospital stay than the control group（P < 0.05）. Conclusion Ulina⁃ statin combined with BALF can effectively improve local inflammatory response and lung function，and optimize blood gas in patients undergoing mechanical ventilation due to respiratory failure caused by pulmonary infection

Objective To investigate the normal reference interval of specific thyroid⁃stimulating hormone （TSH）in women during pregnancy in Sichuan province of China. Methods TSH test results were collected in pregnant women in obstetrics or gynecology outpatient clinic of the Second West China Hospital of Sichuan University between January 1，2015，and December 30，2020. Reference intervals were established according to whether the thyroid peroxidase antibodies（TPOAb）was positive or not and all procedures were conducted based on the docu⁃ ment CLSI EP28⁃A3 by the Clinical Laboratory Standards Institute. Results A total of 14，332 pregnant women in the TPOAb⁃negative group and 10，254 pregnant women in the TPOAb⁃positive group who met the criteria were included. The median TSH levels were lowest in early pregnancy，highest in late pregnancy，and in between in mid⁃ pregnancy in both groups，with consistent trends. According to the CLSI EP28⁃A3 document，we established the reference intervals of TSH in early，mid and late pregnancy for the TPOAb⁃negative group were 0.02 ~ 5.23 mIU/L， 0.03 ~ 5.24 mIU/L and 0.37 ~ 5.68 mIU/L，respectively；for the TPOAb⁃positive group were 0.23 ~ 4.73 mIU/L， 0.35 ~ 4.67 mIU/L，0.43 ~ 4.75 mIU/L，respectively. Conclusions It is essential to establish specific reference intervals for serum TSH during pregnancy，and thyroid hormone changes should be monitored throughout pregnancy in TPOAb⁃positive women.

Objective To explore the predictive effect of mir⁃27a and mir⁃138⁃5p on postoperative survival of patients with esophageal cancer and their relationship with recurrence and metastasis. Methods From January 2014 to January 2017，300 suspected esophageal cancer patients according to the pathological examination results， were divided into esophageal cancer group（n = 70），and esophagitis group（n = 230），and 70 healthy physical examination patients were selected as health group. The expression level of miR⁃27a and miR⁃138⁃5p in serum of three groups was detected by fluorescence quantitative PCR. The correlation between the expression of serum mir⁃ 27a and mir⁃138⁃5p and postoperative recurrence and metastasis was analyzed，and the predictive value of serum mir⁃27a and mir⁃138⁃5p for postoperative survival of patients with esophageal cancer was evaluated. Results In all the three groups，the expression of serum mir ⁃ 27a mRNA was gradually down regulated，while mir ⁃ 138⁃5p mRNA up⁃regulated（P < 0.05）. Clinical stage，degree of radical resection and the relative expression of miR⁃27a and miR ⁃138⁃5p mRNA were independent factors influencing the recurrence and metastasis of esophageal cancer （P < 0.05）. Compared with the death group，the expression level of miR⁃27a mRNA in the survival group was lower， but that of miR⁃138⁃5p mRNA was higher（P < 0.05）. The AUC of serum miR⁃27a and miR⁃138⁃5p for predicting postoperative survival of esophageal cancer were 0.773，0.731 and 0.829，respectively. Conclusion MiR⁃27a and miR⁃138⁃5p have significant predictive value for postoperative survival of patients with esophageal cancer，and are correlated with postoperative recurrence and metastasis.

Objective To investigate and analyze the molecular typing，clinicopathological characteristics and prognosis of breast cancer patients from different regions and nationalities in Guangxi Zhuang Autonomous Region. Methods A total of 1，586 cases with stage Ⅰ⁃Ⅲ breast cancer who were treated in Guangxi Medical University Cancer Hospital from January 1，2015 to December 31，2018 were included in the study. The clinical and pathological characteristics and the relationship with prognosis of four subtype were compared and analyzed. Results The rates of luminal A，luminal B，HER⁃2 overexpression，and triple negative were 14.9%，55.0%，17.7%， and 12.4%，respectively. There were significant differences in age of onset，tumor stage，tumor size，pathological type and number of lymph node metastasis between the groups（all P < 0.05）. Cox analysis showed that molecular typing，tumor size and number of lymph node metastasis were the independent prognostic factors for OS，while molecular typing，lymph node metastasis was the independent prognostic factor for DFS. Subgroup analysis showed that the OS rate of Zhuang nationality was significantly lower than that of Han nationality（5⁃year OS rate：94% vs. 97.8%，χ2 = 4.623，P = 0.032）. The OS rete of the population living in Southern and Western Guangxi was significantly higher than that living in Nanning，Eastern and Northern Guangxi（χ2 = 16.012，P = 0.007）. Conclusions The prognosis of breast cancer is related to molecular typing，tumor size，pathological type，lymph node metastasis and other characteristics. There is no significant difference in the classification characteristics of breast cancer in popula⁃ tion from different regions and nationalities in Guangxi，but the differences in lifestyle and economic status of differ⁃ ent regions and nationalities have a certain impact on the prognosis of some types of breast cancer.

Objective To explore the application value of noninvasive prenatal testing（NIPT）in the detection of copy number variation on chromosomes except chromosome 21，18，13 and sex chromosomes. Methods A total of 114 patients with CNV except chromosome 21，18，13 and sex chromosome abnormalities were selected from January 2019 to January 2021. Amniocentesis was performed under the informed consent principle. Chromo⁃ some karyotype analysis and chromosome microarray analysis（CMA）were performed at the same time and patients′ conditions were followed up. Results Among 114 pregnant women with chromosomal copy number variation detected by NIPT，a total of 37 cases of CNVs，representing a percentage of 32.46%（37/114），were detected which were consistent with the results of NIPT，among which 12 cases of CNVs，representing a percentage of 32.43%（12/ 37），had unclear clinical significance. Follow⁃up data showed that 22 pregnancies were terminated，and 90 births were normal while 2 pregnancies were normal. Conclusion NIPT suggested microdeletion and microduplication of fetal chromosomes，so prenatal diagnosis combined with chromosomal karyotype analysis and CMA was recommended to confirm the diagnosis. Parental comparison was performed according to the results if necessary，so as to provide advice and basis for clinical genetic counseling.

Objective To evaluate the efficacy of Entecavir（ETV）combined with Wuling Capsule for chronic hepatitis B（CHB）patients. Methods Data of 117 CHB patients were collected from the Second Affiliated Hospital，Guangzhou Medical University from April 2019 and September 2020. Sixty ⁃two patients received ETV 0.5 mg/d + Wuling Capsule 1.75 g/d（treatment group）and 55 patients received ETV 0.5 mg/d（control group）for 24 weeks. Biochemical and virological indexes during the treatment were collected. The differences of liver function indexes at baseline，the 4th week，the 12th week，and the 24th week were studied by repeated measures analysis of variance，while the differences in the normalization rate of liver function，decrease of liver fibrosis，HBV DNA negative conversion rates and HBeAg negative conversion rates between treatment group and control group were evaluated by independent samples t test，Mann⁃Whitney U test，and chi⁃square test. The factors of normalization of liver function was evaluated by logistic regression. The median time to cumulativly achieve normal ALT level was evaluated by Kaplan⁃Meier. Results The decrease of ALT，AST level at the 4th week，the 12th week，and the 24th week after treatment was statistically significant when compared with that of the control group（P < 0.05）. The most significantly decrease of ALT，and AST level occurred at the 4th week. The decrease of TBIL level and liver fibrosis （HA，LN，IV⁃C and PIIINP levels）were statistically significant when compared with the control group（P < 0.05）. In treatment group，the ALT，AST and TBIL normalization rate at the 24th week was 90.3%，80.6% and 48.3% respectively，significantly higher than that of the control group（P < 0.05）. Logistic regression analysis found that the treatment group was protective factor correlated with ALT，AST and TBIL normalization rate（ORALT=12.056， P＜0.05、OR AST = 8.56，P＜0.05，ORTBIL=2.58，P＜0.05）. HBV DNA negative conversion rate and HBeAg negative conversion rate in the treatment group were not statistically significant when compared with those in the control group（χ2 = 3.81，P > 0.05；χ2 = 2.23，P > 0.05）. The median time to cumulatively achieve normal ALT level were 24 weeks in the treatment group and 36 weeks in the control group（P＜0.05）. Conclusions Faster and better recovery of liver function can be achieved through Entecavir（ETV）combined with Wuling Capsule for CHB patients，which provides effective new evidence to optimize the outcomes for the re ⁃ combination of current medicine.

Gastroesophageal reflux disease（GERD）is a common chronic digestive diseases，which is easy to relapse and its pathogenesis is varied，and the spirit of psychological factors often play a key role in them. Psychological factors always play the important role in the pathogenesis and progression of GERD by influencing the mechanisms of esophageal motility and perception，gastric and duodenal motility and central sensory sensitization， and the intervention and treatment of mental factors also achieved good results，in which the selective serotonin reuptake inhibitors（SSRIs）has been recognized for its significant effects. This review summarized the possible mechanism of mental factors in the pathogenesis of GERD and the mechanism and specific application of SSRI in the treatment of GERD，so as to provide clinical reference for the application of SSRI in the clinical treatment of GERD. 

With the aging population increasing rapidly，neurodegenerative diseases have become the main cause of the high morbidity and disability of the elderly，causing a significant social and economic burden， and has received more and more attention. Because of their hidden onset，slow development，and complicated pathophysiological changes，no clear，specific，and reliable laboratory method for early diagnosis is available at present. Raman spectroscopy is an optical technology that detects the inelastic scattered light generated by the inter⁃ action between light and matter. It provides chemical fingerprint information of cells，tissues or biological fluids by detecting scattered light of molecules. More and more biomedical applications show Raman spectroscopy has the potential to detect new biomarkers. It can quickly and accurately screen the susceptibility and incidence of diseases， and has broad application prospects in the study of clinically relevant biological species，disease pathogenesis and diagnosis. The prospects of Raman spectroscopy for early diagnosis of neurodegenerative diseases are summarized in this article.