To systematically synthesize evidence on multiple KRAS G12C inhibitors(KRAS G12C inhibitors, KRAS G12Ci) as monotherapy within a unified population and recommended-dose framework, establish a comparable benchmark range of efficacy and safety for previously treated patients with advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC), and explore potential effect modifiers.

Objective:To evaluate the short-term efficacy of minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients using subtalar arthroscopy assisted by preoperative musculoskeletal ultrasound to localize the lateral calcaneal branch of the sural nerve and a medial calcanetalar distractor.Methods:The clinical data of the 52 patients with diabetes mellitus were retrospectively analyzed who had been treated for Sanders Ⅱ and Ⅲ calcaneal fractures from March 2016 to August 2020 at Department of Traumatic Orthopedics, The Third Affiliated Hospital of Soochow University. There were 34 males and 18 females with an age of (61.7±14.5) years. According to the Sanders' classification, there were 23 cases of type Ⅱ and 29 cases of type Ⅲ. Preoperative musculoskeletal ultrasonography was routinely performed to locate the lateral calcaneal branch of the sural nerve in all patients. The surgical procedures were subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor. Incision healing, local skin paraesthesia and other conditions were observed regularly in all patients. The short-term efficacy was assessed by comparing calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles at pre-surgery, 3 days, 12 months and the last follow-up after surgery, as well as by comparing visual analogue scale (VAS) pain scores, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Maryland scores at pre-surgery, 12 months and the last follow-up after surgery.Results:All the 52 patients were followed up for (23.7±3.2) months after successful surgery. No incision-related complications were reported. The calcaneal radiographic parameters (calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles) at 3 days, 12 months and the last follow-up after surgery were significantly improved compared with the values before surgery ( P<0.05), but there were no significant differences regarding the calcaneal radiographic parameters between 3 days, 12 months and the last follow-up after surgery ( P>0.05). The VAS pain scores, AOFAS ankle-hindfoot scores and Maryland scores at 12 months and the last follow-up after surgery were significantly improved compared with those before surgery ( P<0.05). Conclusion:In the minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients, preoperative musculoskeletal ultrasonography to locate the lateral calcaneal branch of the sural nerve, followed by subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor can lead to good short-term efficacy.

Objective:To evaluate the short-term efficacy of minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients using subtalar arthroscopy assisted by preoperative musculoskeletal ultrasound to localize the lateral calcaneal branch of the sural nerve and a medial calcanetalar distractor.Methods:The clinical data of the 52 patients with diabetes mellitus were retrospectively analyzed who had been treated for Sanders Ⅱ and Ⅲ calcaneal fractures from March 2016 to August 2020 at Department of Traumatic Orthopedics, The Third Affiliated Hospital of Soochow University. There were 34 males and 18 females with an age of (61.7±14.5) years. According to the Sanders' classification, there were 23 cases of type Ⅱ and 29 cases of type Ⅲ. Preoperative musculoskeletal ultrasonography was routinely performed to locate the lateral calcaneal branch of the sural nerve in all patients. The surgical procedures were subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor. Incision healing, local skin paraesthesia and other conditions were observed regularly in all patients. The short-term efficacy was assessed by comparing calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles at pre-surgery, 3 days, 12 months and the last follow-up after surgery, as well as by comparing visual analogue scale (VAS) pain scores, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Maryland scores at pre-surgery, 12 months and the last follow-up after surgery.Results:All the 52 patients were followed up for (23.7±3.2) months after successful surgery. No incision-related complications were reported. The calcaneal radiographic parameters (calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles) at 3 days, 12 months and the last follow-up after surgery were significantly improved compared with the values before surgery ( P<0.05), but there were no significant differences regarding the calcaneal radiographic parameters between 3 days, 12 months and the last follow-up after surgery ( P>0.05). The VAS pain scores, AOFAS ankle-hindfoot scores and Maryland scores at 12 months and the last follow-up after surgery were significantly improved compared with those before surgery ( P<0.05). Conclusion:In the minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients, preoperative musculoskeletal ultrasonography to locate the lateral calcaneal branch of the sural nerve, followed by subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor can lead to good short-term efficacy.

Objective:To document any effect of combining kinesiotaping (KT) with Monitored Rehab Systems biofeedback training (MRS training) on the recovery of knee function after anterior cruciate ligament reconstruction (ACLR).Methods:Twenty-two patients after ACLR were randomly divided into an MRS group and a combined group, each of 11. In addition to conventional rehabilitation training, the MRS group had placebo taping in place during their MRS training, while the combined group had KT applied. Each training session lasted 45 minutes, with three sessions per week. Before the experiment and after 8 weeks of treatment, the affected foot support phase, impulse of each area of the affected foot′s sole, and lower limb reaction time were measured.Results:Significant improvement in the affected foot′s support phase and lower limb reaction time was documented in both groups, as well as in the average impulse percentage of the affected foot′s plantar forefoot area (F area), mid-foot area (MF area), and heel area (H area). All were significantly better in the combined group than in the MRS group, on average.Conclusion:Supplementing MRS biofeedback training with kinesiotaping can more effectively improve the knee joint functioning and postural control of patients after ACLR surgery. The combination is worthy of clinical promotion and application.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To investigate the effect of daily soft brace wearing on plantar dynamics during walking in patients with chronic ankle instability(CAI). Methods A total of 52 patients with unilateral chronic ankle instability(CAI)in Beijing Rehabilitation Hospital from February,2021 to January,2023 were randomly divided into control group(n=26)and experimental group(n=26).Both groups underwent an eight-week exercise training program.The control group wore placebo brace dur-ing daily activities,while the experimental group wore soft ankle brace.Plantar dynamic parameters were mea-sured using a pressure plate system during walking,including peak plantar pressure and plantar impulse before and after intervention. Results Six participants dropped out in the control group and five in the experimental group,resulting in a final inclu-sion of 41 participants.After intervention,there was no significant difference in peak plantar pressure and im-pulse on the affected side in the control group among different areas(P＞0.05).In the experimental group,the peak pressure and impulse in the heel medial,heel lateral and forefoot medial areas increased(|t|＞4.192,P＜0.001),while the peak pressure and impulse in the midfoot and lateral forefoot areas decreased(t＞2.984,P＜0.05);the peak pressure and impulse in the heel medial,heel lateral and forefoot medial areas were higher in the experimental group than in the control group(|t|＞2.126,P＜0.05),and the peak pressure and impulse were low-er in the midfoot and forefoot lateral areas(t＞2.133,P＜0.05). Conclusion Wearing a soft brace during daily activities may optimize the distribution of peak plantar pressure and plan-tar impulse on the affected side in patients with CAI,which may prevent recurrence of sprains.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

Objective:To explore the possible pharmacodynamic material basis and mechanism of Shaogan Fuzi Decoction in the treatment of rheumatoid arthritis through ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HRMS/MS) combined with network pharmacology and molecular docking method.Methods:The blood components of Shaogan Fuzi Decoction were analyzed by UPLC-HRMS/MS; the targets of blood components in Shaogan Fuzi Decoction were predicted by PubChem database and Swiss Target Prediction database; DrugBank database, Therapeutic Target Database (TTD) and GeneCards database were used to screen rheumatoid arthritis-related targets, and Venn map of common targets was obtained; the protein interaction network was constructed by STRING database, and the key targets and key components were screened; GO function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID 6.8 database; the "blood component-target-pathway" network was constructed by Cytoscape 3.2.1 software; Autodock software was used to verify the molecular docking between the predicted key components and key targets in the network.Results:Totally 26 blood components of Shaogan Fuzi Decoction, 526 related targets, 478 related targets of rheumatoid arthritis, and 111 common targets were obtained; the key components such as tangeretin, kaempferol, glycyrrhetinic acid, liquiritigenin, quillaic acid and glabrolide were screened, which acted on key targets such as TNF, IL6, VEGFA, PTGS2, JUN and PPARG. They were mainly involved inflammatory response, steroid metabolic process, response to lipopolysaccharide, extracellular region, cytoplasm, RNA polymerase Ⅱ transcription factor activity, steroid bindingand other biological processes. It mainly regulated steroid hormone biosynthesis, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathway, rheumatoid arthritisand other signaling pathways. Molecular docking results showed that the key components had good binding activity with key targets.Conclusion:Shaogan Fuzi Decoction may act on TNF, IL6, VEGFA, PTGS2, JUN, PPARG and other targets through tangeretin, kaempferol, glycyrrhetinic acid and other blood components to regulate PI3K-Akt and other signaling pathways, inhibiting cell proliferation and promoting apoptosis, reducing inflammation, to treat rheumatoid arthritis.

Objective:To investigate the potential risk factors for cryptogenic stroke (CS) in patients with patent foramen ovale (PFO).Methods:Patients underwent PFO closure in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from June 2018 to December 2021 were enrolled retrospectively. Transesophageal echocardiography was used to evaluate the morphological characteristics of foramen ovale and right-to-left shunt (RLS). Multivariate logistic regression analysis was used to determine the independent risk factors for CS in patients with PFO. Results:A total of 203 patients with PFO were enrolled. Their age was 41.9±14.3, and 116 patients (57.1%) were male. There were 102 patients in CS group and 101 patients in non-stroke group. The age, body mass index, systolic blood pressure and diastolic blood pressure, and the constituent ratios of male, hypertension, diabetes, hyperlipidemia and smoking of the CS group were significant higher than those of the non-stroke group (all P<0.05). The PFO channel of the CS group was longer, wider and more combined with resting RLS (all P<0.05). Multivariate logistic regression analysis showed that systolic blood pressure (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.022-1.111; P=0.003), PFO length ( OR 1.124, 95% CI 1.004-1.258; P=0.043) and resting RLS ( OR 5.449, 95% CI 2.283-13.004; P<0.001) were the independent risk factors for CS in patients with PFO. Conclusion:Systolic blood pressure, PFO length and the presence of resting RLS are the independent risk factors for CS in patients with PFO.