Recurrent implantation failure （RIF） refers to the situation where couples facing infertility undergo multiple IVF-ET cycles and transfer multiple high-quality embryos， yet are unable to achieve embryo implantation or clinical pregnancy. The causes of RIF are multifaceted and can be influenced by many factors that may impact the outcome of IVF-ET assisted pregnancy. Despite this， there is ongoing debate regarding the definition of RIF， as well as the screening， diagnosis， and treatment approaches. This confusion largely stems from differences between current domestic and foreign guidelines and consensus. In order to provide clarity on this issue， this article aims to offer reference opinions on the standardized clinical diagnosis and treatment of RIF， based on recent research progress as well as both domestic and foreign guidelines and consensus.

Endometrial receptivity is key to clinical pregnancy by in vitro fertilization-embryo transfer （IVF-ET） technique. Endometrial thickness （EMT） is a major index for pregnancy monitoring， but the optimal time indicating endometrial receptivity is controversially uncertain. Multiple studies have demonstrated the correlation between EMT and IVF pregnancy outcomes and EMT of a moderate range is essential for good pregnancy outcomes and a thin endometrium produces negative pregnancy outcomes. In this paper， we reviewed the research on the impact of EMT on IVF-ET pregnancy outcomes in terms of timing of EMT measurement， clinical pregnancy rate， live birth rate， ectopic pregnancy rate， placenta praevia， and low birth weight， investigating the mechanism of occurrence and treatment of thin endometrium so as to provide clinical references for improving IVF pregnancy outcomes.

Objective To study the effect of mitochondrial reactive oxygen species （ROS） on male fertility and its application value in assisted reproduction so as to provide a new method for fertility assessment and etiological treatment of male infertility. Methods The relationship between sperm ROS and male infertility， sperm nuclear DNA integrity and sperm membrane function was analyzed. Then the relationships of the ROS of sperms for fertilization with fertilization rate， cleavage rate， embryo rate and pregnancy outcome were analyzed. Results （1） The percentage of the high ROS in sperm membrane of the male infertility group was significantly higher than that of the normal fertility group （P < 0.01）， but there was no statistical difference in the percentage of the high ROS in the sperm mitochondria between the two groups. （2） The normal rate of sperm membrane function in the normal group was significantly higher than that in the abnormal group （P < 0.01）， but there was no significant difference in the sperm DNA fragmentation index （DFI） between the groups. （3） There was significant difference in the fertilization rate between the IVF control group and IVF observation group， but no significant difference was seen in the cleavage rate， excellent embryo rate and clinical pregnancy rate between the groups. Conclusion Sperm ROS is related to male fertility to some extent. Abnormal ROS may lead to impaired sperm membrane function and affect sperm fertilization ability， thus affecting male fertility. The detection of ROS in sperm can be used as a new method to evaluate male fertility and provide a basis for diagnosis or treatment of male infertility. For patients with ART or infertility， the appropriate time to conceive can be selected according to the sperm ROS level.

Objective To investigate the regulation of SIRT1 on ovarian granulosa cell in women with poor ovarian response. Methods A total of 60 women who underwent IVF/ICSI-ET were included in this study， 30 women in poor ovarian response （POR） group and 30 women in normal ovarian response （NOR） group. The granulosa cells in follicular fluid were isolated and purified by density gradient centrifugation. The granulosa cells of POR group were treated with SIRT1 agonist resveratrol （RESV） or inhibitor EX527， respectively， and the control group was granulosa cells treated without drugs. mRNA levels of SIRT1 and key enzymes of steroid hormone synthesis （StAR， CYP19， CYP17） in granulosa cells were detected by qPCR. The levels of SIRT1， steroid hormone synthesis key enzymes protein and apoptosis-related protein （Bcl-2， Caspase-3） in granulosa cells were detected by Western blot. The apoptosis rate of granulosa cells was detected by TUNEL method. Determination of estradiol in granulosa cell culture medium by chemiluminescence. Results The mRNA and protein levels of SIRT1 in granulosa cells in POR group were lower than those in NOR group （P = 0.003， P < 0.001）. RESV up-regulated SIRT1 mRNA and protein levels （P < 0.001）， up-regulated mRNA and protein levels of steroid hormone synthesis key enzyme （P < 0.05）. EX527 down-regulated SIRT1 mRNA and protein levels （P = 0.023， 0.001）， down-regulated mRNA and protein levels of steroid hormone synthesis key enzymes （P < 0.05）. After RESV treatment， the apoptosis rate of granulosa cells was decreased （P < 0.001）， the Bcl-2 protein level was increased （P < 0.001）， and the Caspase-3 protein level was decreased （P < 0.001）. After EX527 treatment， the apoptosis rate of granulosa cells was increased （P < 0.001）， the Bcl-2 protein level was decreased （P = 0.003）， and the Caspase-3 protein level was increased （P < 0.001）. Conclusion The SIRT1 level in granulosa cells of POR women was lower than that of NOR women. RESV up-regulated SIRT1 expression in granulosa cells. SIRT1 inhibited granulosa cell apoptosis， increased the level of steroid hormone synthesis key enzyme， and promoted estradiol synthesis in granulosa cell. Therefore， SIRT1 activators such as RESV may be a therapeutic agent to improve ovarian reactivity and increase the number of oocytes obtained in women with POR.

Objective To investigate the relationship of the expression of nucleotide?binding oligomerization domain?like receptor protein 3 （NLRP3） and phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in the serum of male infertility patients with the levels of sex hormones and semen quality. Methods A total of 80 male infertile patients admitted to our hospital from May 2021 to April 2023 were enrolled as the research subjects， who were divided into oligozoospermia group （n = 47） and asthenozoospermia group （n = 33） based on semen quality. Meanwhile， 50 male healthy patients who underwent health examinations in our hospital during the same period were recruited as the control group. The level of serum NLRP3 and PTEN were determined by ELISA， and their relations with the sex hormone levels and semen quality were analyzed. Results Compared with the control group， the semen quality as well as the levels of testosterone （T） and serum PTEN in the patients were significantly reduced （P <0.05）， while the levels of follicle?stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， prolactin （PRL） and serum NLRP3 were significantly increased （P < 0.05）. Compared with the oligospermia group， the sperm concentration， semen volume， and the levels of FSH， T， serum NLRP3， and PTEN in the asthenospermia group were significantly increased （P < 0.05）， the sperm motility and forward motility sperm rate （PR） were significantly decreased （P < 0.05）， and there were no significant differences in the levels of LH， E2， and PRL （P > 0.05）. Through Pearson correlation analysis， the level of serum NLRP3 was negatively correlated with the semen volume， sperm motility， and the levels of PR and T， and significantly positively correlated with the levels of FSH， LH， E2， and PRL （P < 0.05）； The PTEN expression was significantly positively correlated with the sperm concentration， semen volume， sperm motility and the levels of PR and T， and negatively correlated with the levels of FSH， LH， E2， and PRL （P < 0.05）. Conclusion The level of serum NLRP3 is decreased and the PTEN level is increased in male infertile patients. Both of them are correlated with sex hormones and semen quality.

Objective To explore the effects of different endometrial preparation regimens on the pregnancy and obstetrical outcomes of single euploid blastocyst transfer after preimplantation genetic testing for aneuploidies （PGT-A）. Methods The clinical data on patients with single euploid blastocyst transfer after PGT-A in our center from September 2015 to July 2021 were analyzed retrospectively. According to the different preparation regimens， the patients were divided into a natural cycle group （n = 80 cycles） and a hormone replacement cycle group （n = 259 cycles）. The differences of pregnancy and obstetrical outcomes between the two groups were compared. Binary logistic regression was used to explore the influencing factors of pregnancy and obstetrical outcomes after PGT-A. The pregnancy outcomes of different endometrial preparation regimens were further explored by age stratification. Results As compared with that in the natural cycle group， the rate of high-quality blastocyst was significantly higher in the hormone replacement cycle group， but the live birth rate was lower and the abortion rate was higher （P < 0.05）. There was no statistical difference in the clinical pregnancy rate between the two groups. The incidence of cesarean section and macrosomia was higher in the hormone replacement cycle group than that in the natural cycle group， while the rate of low birth weight was lower， but there were no significant differences （P > 0.05）. Binary logistic regression showed that female age was an independent influencing factor of abortion. Female age and the days of blastocyst development were independent influencing factors of live birth. However， endometrial preparation regimen was not a factor affecting pregnancy and obstetrical outcomes （P > 0.05）. The results of further analysis showed that the live birth rate in the natural cycle group was significantly higher than that in the hormone replacement cycle group， while the abortion rate in the natural cycle group was significantly lower than that in the hormone replacement cycle group for female patients aged over 35 （P<0.05）. Conclusions The endometrial preparation regimens did not affect the pregnancy and obstetrical outcomes of patients receiving single euploid blastocyst transfer after PGT-A. However， in the older patients， the natural cycle regimen can obtain a higher live birth rate and a lower abortion rate.

Objective To explore the value of prophylactic anticoagulation in the 28?day prognosis of patients with severe COVID?19. Methods The clinical data of COVID?19 patients admitted to Guangdong Provincial People's Hospital from December 2022 to January 2023 were collected， including age， gender， past medical history， routine blood test， liver and renal function， procalcitonin， coagulation function， Padua prediction score， antiviral therapy， hormonotherapy， immunotherapy and anticoagulation therapy. The patients were divided into an anticoagulation group and a non?anticoagulation group. The differences in various indicators were compared between the two groups. Cox regression was performed to assess the independent risk factors for 28?day mortality and the anticoagulation efficacy between the subgroups. Results Among 158 patients， 128 received anticoagulation； There were significant differences between the two groups in case number of hypertension and critical condition， lymphocyte count， prothrombin time， D?dimer， and case number of immunotherapy. COX logistic regression showed that anticoagulation （HR = 2.25， 95%CI： 1.01 ~ 5.01， P = 0.048） was an independent risk factor for all?cause mortality of COVID?19 patients within 28 days. Subgroup analysis showed that anticoagulation therapy led to an increase in the 28?day mortality as level of procalcitonin of ≥ 0.5 pg/mL （HR = 2.72， 95%CI： 1.05 ~ 7.04） or D?dimer of < 2 000 ng/mL （HR = 9.16， 95%CI： 1.63 ~ 51.48）. Conclusions Prophylactic anticoagulation did not reduce all?cause mortality of COVID?19 within 28 days.

Objective To explore the early predictors of the development of the novel coronavirus infection （COVID-19） into severe and critical forms. Methods COVID-19 patients hospitalized in the Department of Intensive Care Medicine， Infection ward， Respiratory and Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as the study objects， and were divided into mild/medium group， severe group， and critical group according to the severity of illness during hospitalization. General clinical data and early laboratory results of the three groups were collected and compared. Results A total of 242 patients with novel coronavirus infection were included， including 117 mild/medium patients， 55 severe patients， and 70 critically severe patients. There were 165 males and 77 females with a median age of 70 （59，80） years. The age， sex， diabetes， heart disease， stroke， combined pneumonia， combined bloodstream infection， APACHE Ⅱ score， respiratory rate on admission， systolic blood pressure， and early white blood cell count （WBC）， lymphocyte count （LYM）， urea， creatinine， albumin， C-reactive protein， D-dimer， interleukin-6 （IL-6）， and calcium reduction of patients in the three groups had significant （all P < 0.05）. Ordered logistic regression shows， previous heart disease， stroke， combined bloodstream infection， WBC， high IL-6 level， and low LYM level were independent risk factors for severe and critical COVID-19 infection ［odds ratio （OR） and 95% confidence interval （95%CI） were 3.253（1.694 ~ 6.246）， 5.251（2.378 ~ 11.592）， respectively. 6.920（2.499 ~ 19.189）， 1.111（1.041 ~ 1.186）， 1.003（1.001 ~ 1.006）， 0.571（0.353 ~ 0.926）］. ROC curve analysis showed that WBC， LYM， IL-6 and their combined detection had certain predictive value for the severity of COVID-19 （all P < 0.05）， and the combined detection of WBC， LYM and IL-6 had better predictive value than a single indicator （P < 0.05）. Conclusion Previous heart disease， cerebrovascular disease， early combination of bloodstream infection， high levels of IL-6， white blood cell count， and low lymphocyte levels at admission were independent risk factors that helped to predict the severity of COVID-19 infection early. The combined detection of WBC， LYM and IL-6 has certain predictive value for the development of severe and critical COVID-19.

Objective To investigate the correlation between the proportion of peripheral blood follicular T helper cells （Tfh cells） and intracellular interleukin-21（IL-21） content with blue light retinal injury. Methods Brown Norway（BN） rats were randomly divided into 4 groups and were exposed to blue light for 3 hours a day to establish retinal light damage model. According to the duration of illumination， the rats was divided into 0 days （control group）， 3 days （3 d group）， 7 days （7 d group） and 14 days （14 d group）. The proportion of Tfh cells and content of IL-21 in Tfh cells in peripheral blood of each group was detected by flow cytometry and ELISA separately after illumination. Electroretinogram （ERG） was used to evaluate retinal function. The changes of fundus in rats were observed by fundus photography. The thickness of outer nuclear layer of retina was analyzed by HE staining. Results After retinal blue light injury， with the extension of illumination time，the proportion of Tfh cells in peripheral blood and intracellular IL-21 content both increased （P < 0.05）. ERG showed that retinal function decreased after light damage and aggravated with the extension of illumination time， the latency and amplitudes of A-wave and B-wave increased and decreased respectively （P < 0.05）. The retinal fundus of rats showed depigmentation in 3 d， and the retinal vessels became thinner and exudate with the extension of illumination time. HE staining showed that the outer nuclear layer of retina （ONL） became thinner （P < 0.05）. Correlation analysis indicated that the proportion of Tfh cells in peripheral blood and the intracellular IL-21 content could jointly reflect the degree of injury （P < 0.000 1）， and the proportion of Tfh cells in peripheral blood was negatively correlated with ONL thickness and the amplitude of a and b waves， positively correlated with the peak time of a and b waves， （P < 0.0001）. Conclusion The proportion of Tfh cells in peripheral blood and the intracellular IL-21 content were increased after blue light damage to retina， and were significantly increased with the extension of light time with a certain correlation.

Objective To explore the molecular mechanism of prolonged atrial repolarization in rats with reperfusion atrial arrhythmia. Methods Sixteen Langendorff isolated heart perfusion models made by male SD rats were randomly divided into control group （group C，n = 8） and hypothermic ischemia-reperfusion group （group IR，n = 8）. According to the occurrence of atrial arrhythmia after reperfusion，group IR was further subdivided into reperfusion non-atrial arrhythmia subgroup （group N-RAA） and reperfusion atrial arrhythmia subgroup （group R-AA ）.Group C was perfused with 37 ℃ K-H solution for 120 min. In group IR， the isolated heart was perfused with 37 ℃ K-H solution for 30 min and stopped， and the isolated heart was perfused with 4 ℃ Thomas solution （20 mL/kg） for 60 mins. When the heart stopped for 30 mins， the isolated heart was perfused with a half dose of 4 ℃ Thomas solution （10 ℃）. During cardioplegia， the isolated heart was protected by low temperature Thomas solution （4 ℃）， and then reperfused for 30 mins with 37 ℃ K-H solution. The monophasic action potential （MAP） of the right atrium was recorded at balanced perfusion for 30 mins （T₀），balanced perfusion for 105 mins in group C/reperfusion for 15 mins in group IR（T₁） and balanced perfusion for 120 mins in group C/reperfusion for 30 min in group IR（T₂）； The duration of 50% and 90% repolarization of monophasic action potential （MAPD₅₀ and MAPD₉₀） was measured. After electrophysiological monitoring， the expression of Kir2.1 and CaMKⅡ in right atrium was detected by Western blot. Results Compared with T₀， MAPD₅₀ and MAPD₉₀ at T₁ and T₂ were significantly prolonged in group R-AA （P < 0.05）， and MAPD₉₀ at T₁ and T₂ in group R-NAA and group R-AA were significantly longer than those in group C （P < 0.05）.Compared with group R-NAA， MAPD₅₀ and MAPD₉₀ in group R-AA were significantly prolonged at T₁ and T₂ （P < 0.05）.The results of Western blot showed that the expression of Kir2.1 in group R-NAA and group R-AA was significantly lower than that in group C （P < 0.05）， and that in group R-AA was significantly lower than that in group R-NAA （P < 0.05）.The expression of CaMKⅡ in group R-NAA and group R-AA was significantly higher than that in group C （P < 0.05）， and the expression of CaMKⅡ in group R-AA was significantly higher than that in group R-NAA. Conclusion The prolonged duration of atrial repolarization in rats with hypothermic ischemia-reperfusion atrial arrhythmia may be related to the down-regulation of Kir2.1 expression and the up-regulation of CaMKⅡ expression.

Objective To investigate the biological role of methyltransferase-like 14 （METTL14）-mediated m6A modification in myocardial infarction （MI）. Methods A total of 40 mice were randomly divided into 4 groups： Sham+AAV9-NC group （n = 10）， Sham+AAV9-METTL14 group （n = 10）， MI+AAV9-NC group （n = 10） and MI+AAV9-METTL14 group （n = 10）. Mice in each group were injected with AAV9-METTL14 or AAV9-NC through the tail vein one week before MI induction. Cardiac function was measured non-invasively by transthoracic echocardiography， and microvascular injury were measured by immunofluorescence. CMECs were isolated from mouse myocardial tissue， and the cells were treated with oxygen-glucose deprivation （OGD）. Results METTL14 was downregulated in MI mouse heart tissue as well as in OGD-treated CMECs. Compared with the Sham+AAV9-NC group， the expression of VE-cadherin was significantly down-regulated （P < 0.05）， ROS levels increased significantly （P < 0.05） in the MI+AAV9-NC group. MI+AAV9-METTL14 suppressed these changes and enhanced cardiac function in mice. Compared with the NC group， a significant increase in mitochondrial ROS levels was observed in the OGD group （P < 0.05）. Knockdown of METTL14 in CMECs exacerbated ROS levels （P < 0.05）， and the addition of USP48 overexpression plasmid reversed these changes （P < 0.05）. Conclusion METTL14 was lowly expressed in MI and mediates mitochondrial dysfunction in CMECs by increasing the m6A modification level of USP48 in CMECs to reduce its stability.

Objective To explore the effects of heparinase （HPSE） on myocardial apoptosis， inflammatory response and oxidative damage in myocardial ischemia reperfusion （MI/R） rats. Methods Sixty SD rats were randomly assigned （1∶1∶1∶1） tocontrol group， I/R group， I/R+shRNA-NC group and I/R+Heparanase-shRNA group. The control group was only threaded without ligation after thoracotomy， and the MI/R model was prepared by ligation of the left anterior descending branch of coronary artery. The western blot assay （WB） was used to detect heart function and markers of heart damage in each group. HE staining and TUNEL staining were used to observe the myocardial pathology. The expression of apoptosis-related proteins （Caspase-3， Bax， Bcl-2） and UPRmt marker proteins （LonP₁， HSP70） were detected by WB. The contents of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by kit. The levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in peripheral blood were detected by enzyme-linked immunosorbent assay （ELISA）. Results HE staining results showed that the myocardium， epimyma and myocardial fibers were intact and normal in control group. However， the myocardial fibers were bent， myoglobin was dissolved， myocardial muscle nucleus was pyknotic and dissolved， and muscle bundle membrane was ruptured in I/R group and I/R+shRNA-NC group. The epimyocardium was intact in I/R+Heparanase-shRNA group. Moreover， the myocardial fiber bending was significantly improved in I/R+Heparanase-shRNA group. Additionally， compared with the control group， the expression levels of CK-MB， cTnI， Mb， Caspase-3 protein， Bax protein， MDA， IL-6， TNF-α and HSP70 in I/R group were significantly increased. And the difference was statistically significant. Furthermore， the expression levels of HR， LVEF， LVWT， Bcl-2 protein， SOD and LonP₁ protein were significantly decreased. Additionally， compared with the I/R+shRNA-NC group， the expression levels of CK-MB， cTnI， Mb， Caspase-3 protein， Bax protein， MDA， IL-6 and TNF-α in I/R+Heparanase-shRNA group were significantly decreased. And the difference was statistically significant. However， the expression levels of HR， LVEF， LVWT， Bcl-2 protein， SOD， LonP₁ and HSP70 were significantly increased. And the difference was statistically significant. Conclusion Down-regulation of HPSE alleviates myocardial injury in ischemia-reperfusion rats by inhibiting oxidative stress， inflammation， and apoptosis. The mechanism may be related to the inhibition of UPRmt signaling pathway.

Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome （XLAS） with mutations in COL4A5 gene， and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type. Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included， and their clinicopathological features and gene mutation characteristics were retrospectively analyzed. Results The mean age of onset of disease in children with XLAS was （3.68 ± 2.07） years old， the mean age at diagnosis （6.56 ± 2.95） years old， 12 cases （37.5%） started with isolated hematuria， 8 cases （25%） started with hematuria and proteinuria， 12 cases （37.5%） started with nephrotic syndrome nephritic phenotype， and the positive family history of the children was found in 11 cases （34.4%）， ocular lesions were found in 3 cases （9.37%）， ear lesions in 6 cases （18.75%）， and 7 cases （21.87%） were found to have developed chronic kidney disease （CKD） in the later follow-up. 21 children underwent renal tissue puncture biopsy， and electron microscopy showed thinning of the basement membrane （diffuse or segmental） in 13 cases （61.9%）， and uneven thickness of the basement membrane in 8 cases （38.09%）； light microscopy showed thinning of the basement membrane in 13 cases （61.9%）； light microscopy showed thinning of the basement membrane in 8 cases （38.09%）； and light microscopy showed thinning of the basement membrane in 3 cases （11.5%）. （38.09%）； light microscopy： focal segmental glomerulosclerosis （FSGS） in 2 cases （9.52%）， mesangial proliferative glomerulonephritis （Ms PGN） in 11 cases （52.38%）， and minimal change disease （MCD） in 8 cases （38.09%）. The type of mutation was categorized as missense mutation in 12 cases （37.5%）， shear site mutation in 9 cases （28.12%）， nonsense mutation in 6 cases （18.75%）， deletion mutation in 3 cases （9.37%）， and code shift mutation in 2 cases （6.25%）. Genetic mutations were present in 22 cases （68.75%）； spontaneous mutations were present in 10 cases （27.02%）. Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease， and the progress is slow， and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage， so it is important to improve the genetic test for this disease as early as possible， and to make reasonable drug choices to predict the prognosis scientifically.

Objective To explore the clinical efficacy and safety of low-intensity pulse ultrasound in the treatment of medial painful knee osteoarthritis. Methods A total of 10 patients with medial painful knee osteoarthritis were collected and treated with low-intensity pulsed ultrasound. VAS visual analogue scores， WOMAC and Lysholm knee osteoarthritis rehabilitation scale scores were performed before treatment， immediately after treatment， 1 week， 2 weeks and 4 weeks after treatment. The efficacy and safety were compared before and after treatment. The ultrasound images before and after treatment were compared to verify its safety. Result VAS， WOMAC and Lysholm scores were statistically significant before and immediately after treatment， 1 week and 2 weeks after treatment （P　<　0.05）， but there was no statistically significant difference between them and 4 weeks after treatment （P > 0.05）. VAS decreased significantly before treatment， immediately after treatment， 1 week after treatment and 2 weeks after treatment， and were （5.26　±　1.12）， （2.76　±　0.92）， （2.74　±　1.26）， （3.42　±　0.93）， respectively. The secondary outcome indicators of WOMAC and Lysholm were significantly changed before treatment， immediately after treatment， 1 week after treatment and 2 weeks after treatment. They were （24.03　±　4.43） and （66.93　±　14.14），（12.75　±　1.63） and （79.86　±　10.82）， （12.76　±　1.82） and （81.93　±　7.67）， （15.17　±　2.73） and （77.08　±　9.73）， respectively. No significant abnormality was found in the ultrasound images before and after treatment. Conclusion low-intensity pulsed ultrasound safely and effectively regulates the peripheral knee nerve in the treatment of painful knee osteoarthritis， providing a new idea for the intervention and treatment of clinical knee osteoarthritis.

Objective To establish a Nomogram predictive model for Neonatal Sepsis （NS） based on the general characteristics and initial complete blood count of neonates. Methods Retrospective analysis was conducted on the clinical data of newborns who were admitted for the first time to NICU and completed blood routine examination after admission in the MIMIC Ⅲ database. The LASSO?Logistic regression was used to investigate the prediction factors of NS， and then Nomogram prediction model was established. Internal validation was performed using bootstrap resampling with 1000 iterations. External validation of the model was performed using the data from newborns admitted to the First Affiliated Hospital of Zhengzhou University. We evaluated the predictive performance by Area Under the Receiver Operating Characteristic Curve （AUROC）， C?index， calibration curve， and decision curve analysis （DCA）. Results Among the 3，001 neonates， 185 were diagnosed with NS. The Nomogram model was constructed based on indicators such as respiratory distress syndrome， gestational age， birthweight， and initial hematological parameters （red blood cell count， white blood cell count， lymphocyte percentage， neutrophil percentage）， exhibiting good predictive performance with an AUROC of 0.860. Satisfactory predictive abilities were confirmed through both internal and external validation. Conclusion This study developed and validated a well?performing Nomogram prediction model. With simple parameters， it can help clinicians identify newborns at high risk early.

Objective To investigate the clinical efficacy of drug eluting stents vs metal bare stents for femoral popliteal arteriosclerosis obliterans. Methods The clinical data of 47 patients with femoral popliteal arteriosclerosis obliterans receiving endovascular therapy from October 2020 to June 2021 were retrospectively analyzed. A total of 24 cases received drug-eluting stents （DES group） and 23 cases underwent metal bare stents （BMS group）. Results All patients successfully completed the operation without any adverse events. There was no statistical difference in ABI between the DES group and the BMS group at 7 days and 3 months after surgery， and ABI growth value of the DES group was higher than that of the BMS group at 6， 12 and 24 months after surgery （P < 0.05）. There was no significant difference in the primary patency rate at 6 months after surgery， However， the primary patency rate in DES group was higher than that in BMS group at 12 and 24 months after surgery （91.7% vs. 65.2%， 83.3% vs. 56.5%， P < 0.05）. For the target lesion revascularization rate of the two groups， DES group had a significant advantage over BMS group （4.0% vs. 26.1%， P < 0.05）. Conclusion DES had better clinical efficacy and advantage over bare metal stent for the treatment of femoral popliteal arteriosclerosis obliterans.

Objective To investigate the effect of ultrasound?guided bilateral superior laryngeal nerve internal branch block combined with endotracheal surface anesthesia in patients with hypertensive cerebral hemorrhage for the duration of postoperative tube insertion. Methods A total of 100 emergency hypertensive intracerebral hemorrhage surgical patients who visited our hospital from October 2021 to April 2023 were included as the research subjects. They were randomly divided into four groups， 25 patients in each group. After surgery， group U received bilateral superior laryngeal nerve internal branch block under guidance of ultrasound combined with endotracheal surface anesthesia， group C1 received bilateral superior laryngeal nerve internal branch block under guidance of ultrasound， group C2 received endotracheal surface anesthesia， and group C3 did not undergo any procedure after surgery. Hemodynamic changes （HR， MAP， and SpO₂） at different time points during the postoperative tube insertion in four groups of patients were recorded. The frequency of restlessness within 10 hours after surgery， the dosage of dexmedetomidine and urapidil， the volume of wound drainage， and the satisfaction of bed nurses were also recorded. Results There was no statistically significant difference in general conditions among the four groups （P > 0.05）. There was no statistically significant difference in HR and MAP at different time points in Group U （P > 0.05）， while the differences among the other three groups were statistically significant （P < 0.05）. At the same time point， the MAP and HR of group U and C1 were significantly lower than those of group C3 （P < 0.05）， and the MAP of group U was significantly lower than that of group C2 （P < 0.05）. There was no statistical difference in SPO2 among the four groups of patients at the same time point （P > 0.05）； The frequency of restlessness， dosage of dexmedetomidine and urapidil， and volume of wound drainage in the U and C1 groups were significantly lower than those in the C2 and C3 groups （P < 0.05）. Except for the difference in restlessness frequency （P < 0.05）， there was no statistical difference in other indicators between group U and C1； There was a statistical difference in satisfaction among the four groups of nurses （P < 0.05， C3 > C2 > C1 > U group）. No nerve block related complications were observed in the U and C1 group. Conclusion Ultrasound?guided bilateral superior laryngeal nerve branch block combined with endotracheal surface anesthesia can maintain hemodynamics steadily of the postoperative patients in the NICU to varying degrees and reduce the frequency of postoperative restlessness， the dosage of sedative and anti?hypertensive drugs， while reducing the flow of wound drainage， and improve the satisfaction of bed nurses.

Objective To investigate the serum C?type lectin domain family 4 member G（CLEC4G） level and its clinical value in patients with Atopic Dermatitis （AD）. Methods The blood samples of 60 AD patients and 29 control patients were collected， and CLEC4G， Interleukin?33 （IL?33）， total immunoglobulin E （tIgE）， specific IgE （specific IgE）， and eosinophil levels were detected. The correlation between CLEC4G level and clinical data of AD patients and IL?33 was analyzed. The risk of AD was evaluated by Logistic regression analysis of CLEC4G， IL?33 and other indicators. Results Compared with the control group， the serum CLEC4G level in AD patients was significantly decreased （359.4 ± 57.3 vs. 521.8 ± 48.1）pg/mL. There was no significant difference in CLEC4G level between childhood， adolescent and adult， male and female AD patients. Compared with tIgE ≤ 100 kU/L group，CLEC4G level was significantly decreased in 100 ~ 200 kU/L group and tIgE ≥ 200 kU/L group， but there was no significant difference between 100 ~ 200 kU/L group and tIgE ≥ 200 kU/L group. Serum CLEC4G level decreased significantly only in the moderate AD group， but had no significant difference among the other groups. The serum level of IL?33 was increased in AD patients， but there was no significant correlation between CLEC4G and IL?33 （r = 0.090， P = 0.495）. Age less than 14 years old and IL?33 were risk factors for the incidence of AD， with OR values of 2.756 and 1.241，95%CI of 1.076 ~ 7.060 and 1.030 ~ 1.495， respectively. CLEC4G was a protective factor for AD （OR = 0.890，95%CI：0.809 ~ 0.979）. Conclusion CLEC4G may be a protective factor independent of IL?33 mediated AD pathogenesis.

Objective To investigate the clinical effects and influencing factors of remote ischemic postconditioning RIPostC in the patients with post stroke fatigue （PSF）. Methods Eighty patients with PSF were randomly divided into experimental group（n = 40） and control group（n = 40）. Patients in both groups received routine drug therapy and rehabilitation training for stroke. The experimental group were additionally given RIPostC for four weeks. They were evaluated with National Institute of Health Stroke Scale（NIHSS）， Barthel Index（BI），Mini-mental State Examination（MMSE），fatigue severity scale（FSS）， Hamilton Anxiety Scale（HAMA）， and Hamilton Depression Scale（HAMD）. Results The score of NIHSS， FSS， HAMA and HAMD in the both groups were decreased， while the score of BI and MMSE were increased （P < 0.01）. The difference in the score of NIHSS， BI， MMSE， FSS， HAMA and HAMD between the two groups before and after treatment showed statistical significance （P < 0.01） and the difference in the score was more significant in the experimental group. The risk factors of FSS were MMSE and HAMA. Conclusion RIPostC can effectively improve the neurological deficits， daily activity ability and cognitive function， alleviate fatigue， anxiety and depression in the patients of PSF. The influencing factors of PSF are cognitive function and anxiety.

Objective To explore the curative effect of pedicled retrograde posterior leg myocutaneous flap in patients with ankle soft tissue defect， and analyze its related factors on patients' sensory function. Methods The data of 120 patients with ankle soft tissue defect who were treated in our hospital from January 2015 to January 2022 and followed up for one year after operation were selected. Among them， 60 cases were repaired with pedicled posterior leg myocutaneous flap （group A）， 40 were repaired with medial foot flap （group B） and 40 were repaired with ankle epithelial flap （group C）. The healing （flap survival， infection， appearance， texture）， sensory function， appearance satisfaction， Baird-Jackson score and complications of patients with ankle soft tissue defect in each group were compared. Results There was no difference in baseline data among the groups （P > 0.05）. Patients with ankle soft tissue defect in each group were observed for one year after flap repair. The survival rate of flap in group A was higher than that in group B and C， and the difference was statistically significant （P < 0.05）. There was no significant difference in infection， appearance， texture and walking function among the groups （P > 0.05）. After flap repair， the sensory function score of group A was better than that of group B and C， and the difference was statistically significant （P < 0.05）. The appearance satisfaction of group A was higher than that of group B and C， showing statistical significance （P < 0.05）. There was no difference in complications after flap repair in each group （P > 0.05）. Conclusion Skin flap should be chosen according to the area， shape and characteristics of the skin flap for patients with ankle soft tissue defect， and pedicled retrograde posterior leg myocutaneous flap has better curative effect， higher survival rate and higher excellent and good rate of ankle function. It is more helpful for limb function recovery of patients with ankle soft tissue defect.

Objective The aim of this study was to investigate the effects of general practice mode combined with duloxetine on psychological status， sleep quality and serum inflammatory cytokines in patients with Fibromyalgia Syndrome （FMS）. Methods A total of 105 FMS patients in Chengde Central Hospital from January 2019 to December 2021 were divided into the combined group （53 cases） and the control group （52 cases） by the random number table method. The two groups were treated with general practice mode combined with duloxetine or duloxetine alone. The single course of treatment lasted for 4 weeks. Their efficacy and safety were evaluated after 2 courses of intervention. Visual analogue scale （VAS）， Hamilton Anxiety assessment scale （HAMA）， Hamilton Depression Scale （HAMD） and Pittsburgh Sleep Quality Index （PSQI） were performed before and after treatment. The pain， psychological status and sleep quality of the patients were evaluated. Blood samples were taken to measure the serum levels of tumor necrosis factor?α （TNF?α）， interleukin?1 （IL?1） and IL?6 before and after treatment. Results The total effective rate in the study group was 96.23%， which was higher than that in the control group （82.69%， P < 0.05）. Compared with those before treatment， VAS， HAMA， HAMD and PSQI scores， serum TNF?α， IL?1 and IL-6 levels in the two groups were all decreased after treatment， and those in the study group were lower than those in the control group （P < 0.05）. There was no statistically significant difference in the incidence of adverse reactions between two groups （7.55% vs. 19.23%， P > 0.05）. Conclusion General practice mode combined with duloxetine was safe and effective in the treatment of FMS， which could significantly relieve anxiety and depression of patients， improve their sleep quality， and reduce the level of serum inflammatory cytokines.

Objective To explore the clinical value of neurography and nerve root sealing in treatment of multilevel lumbar spinal stenosis with lumbar instability using Endo?P/TLIF. Methods A total of 60 patients with multi?segment lumbar spinal stenosis and lumbar instability hospitalized in our hospital were included in this study From January 1， 2022 to June 21， 2022. All patients underwent nerve root closure angiography before surgery to confirm the responsible segments， and then the responsible segments were treated with Endo?P/TLIF. The patients were followed up for 6 months. The basic information on the age， gender， course of disease， surgical time， intraoperative bleeding， hospitalization time， and off?bed ambulation time was collected. Then the data on VAS score， ODI score， JOA score， lumbar lordosis angle， intervertebral height， dural cross?sectional area， sacral inclination angle， pelvic projection angle， and pelvic inclination angle before， right after， 3 months and 6 months after the operation were calculated. The number of responsible segments indicated by MRI and confirmed by nerve root closure angiography and the number of the single segment， double segments， 3 segments， and above finally decompressed were statistically analyzed. Results All patients went through the surgery safely. During the 6?month follow?up， one patient did not return to the hospital for consultation on time， and one patient was out of contact. Finally， the follow?up data of 58 patients were completely collected for statistical analysis. Fifty?five cases were remarkably improved， 2 better， and 1 moderately， 6 months after the operation， with a total effectiveness rate of 100%. The number of unilateral and bilateral single responsible segments confirmed by nerve root angiography and sealing was significantly larger than by MRI （P < 0.05）， but the number of unilateral and unilateral double， or multiple responsible segments was significantly smaller （P < 0.05）. There were statistically significant differences in terms of postoperative VAS score， ODI score， JOA score， VAS score， ODI score， JOA score， lumbar lordosis angle， intervertebral height， dural cross?sectional area， sacral inclination angle， pelvic inclination angle as compared to the preoperative data （P ? 0.05）. The pelvic projection angle was insignificantly improved as compared to the preoperative condition （P ? 0.05）. Conclusion The accurate diagnosis with selective neurography and nerve root sealing improves the confirmation of responsible nerve segments before operation. Base on the accurate diagnosis， multi?segment lumbar spinal canal stenosis with lumbar instability can be effectively treated with Endo?P/TLIF， the responsible segment decompressed， trauma and bleeding reduced， hospital stay shortened， spinal physiological curvature well recovered， and clinical efficacy improved. Therefore， the method is worthy of extensive application in clinical practice.

Objective To investigate the association between single nucleotide polymorphisms （SNPs） of YTHDF1 rs6011668， HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer. Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected. The candidate SNPs were genotyped using Hi?SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing； the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression. Multifactorial logistic regression and Risk Score （RS） model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer. Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers （95% CI：1.128 ~ 8.382， P = 0.028）， and 2.961 times higher risk than CC/TC genotypes carriers （95% CI：1.091 ~ 8.033， P = 0.033）. Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non?tea drinkers， pickled food eaters and fried food eaters（P < 0.05）. In addition， TT genotype carriers had the increased risk of gastric cancer infiltration， lymph node metastasis， distal metastasis and intermediate to advanced stages（P < 0.05）. The RS of the case and control groups were calculated by combining environmental and genetic factors. The higher the RS score， the higher the risk of gastric cancer was found in the RS quartile groups. Compared with the RS < Q25 group， the risk of gastric cancer in the Q25 < RS < Q50， Q50 < RS < Q75 and RS ≥ Q75 groups was 3.090， 9.731 and 19.949， respectively. Conclusion The YTHDF1 rs6011668 mutant genotype may be associated with an increased risk and clinical progression of gastric cancer， and combining environmental and genetic factors could better assess the risk of gastric cancer.

Objective To explore the value of diffusion-tensor imaging （DTI） of different gray matter nuclei in the diagnosis and assessment of prodromal Parkinson's disease （pPD） under logistic regression model. Methods A total of 20 patients with pPD were collected as case group and 28 healthy people as control group （HC group）. All patients were examined by MRI plain scan and DTI. DSI studio was used to post-process the DTI images of all patients. Parameters （FA, MD, AD, RD） of basal ganglia, midbrain and brainstem of patients with pPD and HC group were automatically extracted and statistically analyzed. Logistic regression analysis was used to draw the Receiver Operating Characteristic （ROC） curve to analyze and compare the diagnostic efficacy of individual diagnosis and combined diagnosis of each parameter. And the correlation between the parameters of each group and MMSE score was analyzed. Results There were statistical differences in basal ganglia, midbrain and brain stem in PPD and HC group （P < 0.05）. Under Logistic regression equation model, when the optimal threshold was 0.63, the AUC of PPD was 0.964. The sensitivity and specificity of differential diagnosis were 85.0% and 100% respectively （P < 0.001）. There was correlation between DTI parameters and MMSE score in locus coeruleus in PPD group （P < 0.05）, and the correlation coefficient of FA value in locus coeruleus （r = -0. 646, P = 0.002） was the highest. Conclusions The lesions of basal ganglia, midbrain and brainstem correlated gray matter nuclei in pPD were extensive and different in degree. AD value of locus coeruleus was valuable for quantitative diagnosis of pPD, FA value of locus coeruleus could be used as a characteristic sensitive index for recognition of the severity of dysfunction in pPD patients. Multi-parameter combined diagnosis of DTI under Logistic regression model could effectively improve the diagnostic efficiency, and provide valuable reference for early diagnosis and intervention of pPD.

Percutaneous coronary intervention （PCI） is one of the most important therapeutic measures for coronary heart disease. It can quickly and effectively relieve coronary artery obstruction. Patients with coronary heart disease often suffer from the complication of emotional disorders like anxiety and depression. The incidence of anxiety and depression in patients having undergone PCI is significantly higher in those having not. But anxiety and depression can remarkably increase the major adverse cardiac events （MACE） in patients after PCI. This article reviews the associations， mechanisms and treatments of anxiety and depression after PCI.

Hepatolithiasis is a common biliary tract disease in China and other Asian countries. It has insidious onset， recurrent disease， and may lead to biliary cirrhosis or even cancer in the late stage without intervention. At present， surgery is considered to be the best choice for treatment. In the 21st century of minimally invasive surgery， traditional procedures such as partial hepatectomy， choledochotomy， cholangioenterostomy and liver transplantation can be performed with the assistance of laparoscopy and da Vinci robots， and emerging endoscopic techniques such as endoscopic retrograde cholangiopancreatography （ERCP） and percutaneous transhepatic choledochoscopic lithotripsy （PTCSL） have also been developed， bringing better treatment for patients with hepatolithiasis. As treatment options are becoming more varied， there are also some clinical problems that need to be addressed. In this article， we would like to briefly review the current surgical treatment modalities in order to provide a theoretical basis for optimizing the treatment modalities.