OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of the protein phosphatase 1 regulatory subunit 1B( PPP1R1B) gene and schizophrenia in the Han population of northern Henan province. Methods:Utilizing Psychiatric Genomics Consortium 3 (PGC3) data, the SNPs of PPP1R1B gene which were significantly associated with schizophrenia were screened.Subsequently, totally 1 721 schizophrenia patients and 6 726 healthy controls from the Han population in northern Henan province were recruited for further analysis. The SNP rs907094, located within the PPP1R1B gene was validated, and the clinical symptoms of 386 schizophrenia patients were evaluated using the positive and negative syndrome scale (PANSS). Additionally, expression quantitative trait loci (eQTL) association analysis was conducted to explore the relationship between the rs907094 polymorphism and PPP1R1B gene expression.The PLINK v1.9, Genetic Power Calculater, SPSS 20.0 softwares were used for data analysis. Results:Significant differences in genotype AA, AG, GG(schizophrenia group: AA, 489(28.4%); AG, 848(49.3%); GG, 384(22.3%); control group: AA, 1 450(21.6%); AG, 3 386(50.3%); GG, 1 890(28.1%), χ2=45.418, P<0.05) and allele frequency(schizophrenia group: A, 1 826(53.1%); G, 1 616(46.9%); control group: A, 6 286(46.7%); G, 7 166(53.3%), χ2=43.877, P<0.05) were observed for SNP rs907094 between the schizophrenia group and control group. Individuals carrying allele A were identified to have a higher risk of developing schizophrenia compared to those carrying allele G ( OR=1.288, 95% CI=1.195-1.388). Furthermore, the genotype PPP1R1B gene was found to be associated with the clinical features of schizophrenia. A statistically significant difference was observed in the excitement/hostility factor between AA and GG patients with rs907094 (13.62±5.65, 15.54±4.66)( P<0.05). Additionally, significant differences were noted in the cognitive factor scores between AA and GA genotypes (17.76±5.58, 19.43±5.73)( P<0.05). Conclusions:In the Han population from northern Henan province, the rs907094 polymorphism of the PPP1R1B gene is associated with schizophrenia.And the specific locus may be implicated in arousal/hostility symptoms and cognitive dysfunction.

Objective To compare the efficacy and safety of erector spinae plane block(ESPB)and thoracic paravertebral block(TPVB)in preventing acute post-surgical pain syndrome(PSP)of breast cancer.Methods The following databases,both domestic and international,including Embase,Cochrane Library,Web of Science,PubMed,CNKI,VIP,Wanfang,and Sinomed,were searched via computer to gather clinical randomized controlled trials(RCTs)on ESPB and TPVB for breast cancer patients.The included literature was evaluated using the Cochrane bias risk assessment tool to assess quality,and meta-analysis was performed using Review Manager 5.4 software and Stata 17.0 software.Results This study comprised 14 RCTs,with a total of 1079 patients,including 540 ESPB patients and 539 TPVB patients.The analysis results indicated that there was a significant difference in pain scores during postoperative rest between ESPB and TPVB during 3-4 h(I2=53%,SMD=0.36,95%CI:0.07-0.65,P=0.020)and 5-6 h(I2=80%,SMD=0.53,95%CI:0.05-1.01,P=0.030),with TPVB being superior to ESPB.However,there was no significant difference in pain scores during postoperative rest between ESPB and TPVB at 1-2 h(I2=75%,SMD=0.28,95%CI:-0.03-0.60,P=0.080),7-8 h(I2=89%,SMD=0.24,95%CI:-0.47-0.94,P=0.510),12 h(I2=90%,SMD=0.1,95%CI:-0.40-0.60,P=0.690),24 h(I2=78%,SMD=0.33,95%CI:-0.04-0.70,P=0.080),and 48 h(I2=85%,SMD=-0.05,95%CI:-0.52-0.42,P=0.830).For the pain score during postoperative exercise,there was a significant difference between ESPB and TPVB during 3-4 h(I2=0,SMD=0.29,95%CI:0.09-0.48,P=0.004),7-8 h(I2=48%,SMD=0.37,95%CI:0.00-0.73,P=0.050),and 48 h(I2=0,SMD=0.21,95%CI:0.03-0.39,P=0.020),with TPVB being su-perior to ESPB.There was no significant difference between ESPB and TPVB at 1-2 h(I2=89%,SMD=0.42,95%CI:-0.19-1.03,P=0.180),5-6 h(I2=90%,SMD=0.29,95%CI:-0.67-1.24,P=0.560),12 h(I2=81%,SMD=0.25,95%CI:-0.22-0.72,P=0.300),and 24 h(I2=83%,SMD=0.39,95%CI:-0.10-0.89,P=0.120).There was a statistical difference in the operation time of nerve blocks between the two methods,with ESPB taking less time than TPVB(P＜0.001).However,there was no statistical difference in opioid consumption within 24 h after surgery,incidence of nausea and vomiting,and the first PCIA press time(all P＞0.05).Conclusions Compared to ESPB,TPVB tends to result in a decreased pain score after breast cancer surgery,but it also took longer to perform.There was no significant difference be-tween the two methods in terms of opioid consumption at 24 h after surgery,incidence of nausea and vomiting and the first PCIA press time.

Objective To compare the efficacy and safety of erector spinae plane block(ESPB)and thoracic paravertebral block(TPVB)in preventing acute post-surgical pain syndrome(PSP)of breast cancer.Methods The following databases,both domestic and international,including Embase,Cochrane Library,Web of Science,PubMed,CNKI,VIP,Wanfang,and Sinomed,were searched via computer to gather clinical randomized controlled trials(RCTs)on ESPB and TPVB for breast cancer patients.The included literature was evaluated using the Cochrane bias risk assessment tool to assess quality,and meta-analysis was performed using Review Manager 5.4 software and Stata 17.0 software.Results This study comprised 14 RCTs,with a total of 1079 patients,including 540 ESPB patients and 539 TPVB patients.The analysis results indicated that there was a significant difference in pain scores during postoperative rest between ESPB and TPVB during 3-4 h(I2=53%,SMD=0.36,95%CI:0.07-0.65,P=0.020)and 5-6 h(I2=80%,SMD=0.53,95%CI:0.05-1.01,P=0.030),with TPVB being superior to ESPB.However,there was no significant difference in pain scores during postoperative rest between ESPB and TPVB at 1-2 h(I2=75%,SMD=0.28,95%CI:-0.03-0.60,P=0.080),7-8 h(I2=89%,SMD=0.24,95%CI:-0.47-0.94,P=0.510),12 h(I2=90%,SMD=0.1,95%CI:-0.40-0.60,P=0.690),24 h(I2=78%,SMD=0.33,95%CI:-0.04-0.70,P=0.080),and 48 h(I2=85%,SMD=-0.05,95%CI:-0.52-0.42,P=0.830).For the pain score during postoperative exercise,there was a significant difference between ESPB and TPVB during 3-4 h(I2=0,SMD=0.29,95%CI:0.09-0.48,P=0.004),7-8 h(I2=48%,SMD=0.37,95%CI:0.00-0.73,P=0.050),and 48 h(I2=0,SMD=0.21,95%CI:0.03-0.39,P=0.020),with TPVB being su-perior to ESPB.There was no significant difference between ESPB and TPVB at 1-2 h(I2=89%,SMD=0.42,95%CI:-0.19-1.03,P=0.180),5-6 h(I2=90%,SMD=0.29,95%CI:-0.67-1.24,P=0.560),12 h(I2=81%,SMD=0.25,95%CI:-0.22-0.72,P=0.300),and 24 h(I2=83%,SMD=0.39,95%CI:-0.10-0.89,P=0.120).There was a statistical difference in the operation time of nerve blocks between the two methods,with ESPB taking less time than TPVB(P＜0.001).However,there was no statistical difference in opioid consumption within 24 h after surgery,incidence of nausea and vomiting,and the first PCIA press time(all P＞0.05).Conclusions Compared to ESPB,TPVB tends to result in a decreased pain score after breast cancer surgery,but it also took longer to perform.There was no significant difference be-tween the two methods in terms of opioid consumption at 24 h after surgery,incidence of nausea and vomiting and the first PCIA press time.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of the protein phosphatase 1 regulatory subunit 1B( PPP1R1B) gene and schizophrenia in the Han population of northern Henan province. Methods:Utilizing Psychiatric Genomics Consortium 3 (PGC3) data, the SNPs of PPP1R1B gene which were significantly associated with schizophrenia were screened.Subsequently, totally 1 721 schizophrenia patients and 6 726 healthy controls from the Han population in northern Henan province were recruited for further analysis. The SNP rs907094, located within the PPP1R1B gene was validated, and the clinical symptoms of 386 schizophrenia patients were evaluated using the positive and negative syndrome scale (PANSS). Additionally, expression quantitative trait loci (eQTL) association analysis was conducted to explore the relationship between the rs907094 polymorphism and PPP1R1B gene expression.The PLINK v1.9, Genetic Power Calculater, SPSS 20.0 softwares were used for data analysis. Results:Significant differences in genotype AA, AG, GG(schizophrenia group: AA, 489(28.4%); AG, 848(49.3%); GG, 384(22.3%); control group: AA, 1 450(21.6%); AG, 3 386(50.3%); GG, 1 890(28.1%), χ2=45.418, P<0.05) and allele frequency(schizophrenia group: A, 1 826(53.1%); G, 1 616(46.9%); control group: A, 6 286(46.7%); G, 7 166(53.3%), χ2=43.877, P<0.05) were observed for SNP rs907094 between the schizophrenia group and control group. Individuals carrying allele A were identified to have a higher risk of developing schizophrenia compared to those carrying allele G ( OR=1.288, 95% CI=1.195-1.388). Furthermore, the genotype PPP1R1B gene was found to be associated with the clinical features of schizophrenia. A statistically significant difference was observed in the excitement/hostility factor between AA and GG patients with rs907094 (13.62±5.65, 15.54±4.66)( P<0.05). Additionally, significant differences were noted in the cognitive factor scores between AA and GA genotypes (17.76±5.58, 19.43±5.73)( P<0.05). Conclusions:In the Han population from northern Henan province, the rs907094 polymorphism of the PPP1R1B gene is associated with schizophrenia.And the specific locus may be implicated in arousal/hostility symptoms and cognitive dysfunction.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

BACKGROUND:Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon.It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint,and has achieved good biomechanical results and clinical efficacy.However,whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE:To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS:Ten adult female Yunnan small-ear pigs were selected,and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction(normal group,n=10),and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension-reduction and augmentation system for anterior cruciate ligament reconstruction(tension-reduction group,n=10).One year after surgery,the experimental pigs were sacrificed,and the left and right knee cartilage was taken for hematoxylin-eosin staining,Safranin O-fast green staining,Osteoarthritis Research Society International scoring,and immunohistochemistry staining of type Ⅱ collagen,interleukin-1β,and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the tension-reduction group,there were mild pathologic changes of osteoarthritis,with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage;in the normal group,more severe cartilage damage,with an increased number of empty bone lacunae,loss of chondrocytes near the bone and even the formation of fissures.Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness,flat cartilage surface,a neat cell arrangement in a polar pattern,and no swelling or apoptosis,while in the normal group,the thickness of cartilage tissue was obviously thinner,the cell arrangement was disordered with no polarity,the number of cells was reduced,obvious cartilage fractures and cartilage vacuoles formed,and the absence of cells near the central bone was obvious.The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group(P＜0.05).Immunohistochemical findings showed that the protein expression of type Ⅱ collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group(P＜0.05),and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group(P＜0.05).To conclude,internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction.

BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.

Immunocytokines, employing targeted antibodies to concentrate cytokines at tumor sites, have shown potential advantages such as prolonged cytokine half-lives, mitigated adverse effects, and synergistic antitumor efficacy from both antibody and cytokine components. First, we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications. Notably, anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8⁺ T cells and reinvigorate them to elicit robust antitumor immune responses. Then, we focus on their molecular structures and action mechanisms, striving to elucidate the correlations between diverse molecular structures and their antitumor efficacy. Moreover, our exploration extends to the realm of novel cytokines, including IL-10, IL-18, and IL-24, unraveling their potential in the construction of immunocytokines. However, safety concerns remain substantial barriers to immunocytokines' development. To address this challenge, we explore potential strategies, such as cytokine engineering and prodrug design, which can foster next-generation immunocytokines development. Overall, this review concentrates on the design of molecular structures in immunocytokines, underscoring the direction and focus of ongoing efforts to improve safety profiles while maximizing therapeutic efficacy.

ObjectiveTo investigate the in-brace and short-term correction of 3D-printed scoliosis orthoses. MethodsFrom July to December 2021, 36 patients with adolescent idiopathic scoliosis from Ninth People's Hospital, Shanghai Jiaotong University School of Medicine were selected to complete full-length radiographs of the spine before and immediately after wearing the orthosis. They wore the orthosis more than 20 hours a day, and took radiographs six months later. Cobb angle was calculated. They were assessed with Chinese version of the Scoliosis Research Society's outcomes instrument 22 (SRS-22) before wearing and six months follow-up. ResultsThe mean Cobb angle was (22.10±6.29)° before wearing, and it was (7.85±10.90)° immediately after wearing (t = 4.775, P < 0.01) and (14.33±0.74)° six months follow-up (t = 4.189, P < 0.01). The score of functional status of SRS-22 increased six months follow-up (Z = -2.676, P < 0.01). The Cobb angle immediately after wearing correlated with the Cobb angle six months follow-up (r = 0.826, P < 0.05). Conclusion3D-printed scoliosis orthoses can correct the scoliosis satisfactorily, in-brace and in short-term.