Objective: To evaluate the feasibility of exempting Asian-type DEL pregnant women from anti-D monitoring and RhD immunoglobulin prophylaxis injections by comparing and analyzing the clinical incidence of anti-D alloimmunization between Asian-type DEL pregnant women and true RhD-negative pregnant women. Methods: A total of 165 pregnant women who were initially screened as RhD negative by the saline method and received medical treatment in our hospital from December 2022 to August 2024 were collected as the research subjects. Absorption and elution tests, DEL genotyping, and gene sequencing were used to divide the pregnant women into the Asian-type DEL group and the true negative group. After obtaining informed consent, the following clinical management plan was implemented for pregnant women with Asian-type DEL: exemption from routine anti-D antibody detection, exemption from RhD immunoglobulin prophylaxis, and transfusion of RhD-positive red blood cells. Blood samples of newborns were sent for examination of hemolytic disease of the fetus and newborn (HDFN). The routine management plan was implemented for true negative pregnant women. The incidence of alloimmunization and HDFN was comparatively analyzed between the two groups. Results: Among 165 initially screened RhD negative pregnant women, serological testing and genotyping confirmed 42 as Asian-type DEL, 9 as D variant, and 114 as true negative. Among 42 pregnant women with Asian-type DEL, 3 cases tested positive for HDFN due to receiving RhD immunoglobulin prophylaxis injection. The remaining 39 cases were exempted from anti-D testing after being fully informed of the risk, and did not receive RhD immunoglobulin prophylaxis. The HDFN tests were all negative. In the true negative group, anti-D antibodies were detected in 20 cases, of which 6 cases tested positive for HDFN. A pregnant woman with Asian -type DEL did not show RhD homologous immune response after receiving 2 units of RhD positive red blood cells. Statistical analysis revealed a significantly lower risk of anti-D alloimmunization in Asian-type DEL carriers compared to true D-negative pregnant women (P<0.05). Conclusion: Pregnant women with Asian-type DEL can be exempted from routine anti-D antibody testing and do not require routine RhD immunoglobulin prophylaxis injections.

Objective:To evaluate the application of digital visualization in preoperative planning for surgical clearance of vertebral infection lesions following percutaneous vertebroplasty (PVP).Methods:A retrospective study was conducted to analyze the 13 patients with infectious spondylitis following PVP who had undergone one-stage posterior debridement and interbody bone grafting combined with instrumentation at Department of Spinal Surgery, Zhengzhou Orthopaedics Hospital from January 2016 to December 2022. They were 4 males and 9 females with an age of (71.4±6.5) years. Before surgery, the CT raw data of the patients were imported into software Mimics to reconstruct a three-dimensional model of the spine. After the distribution of bone cement in the model and its relationships with the vertebral plate, pedicle, articular process, and spinal cord were observed, a safe area for spinal canal surgery was designed. Intraoperative operations were carried out according to the preoperative planning. Surgical time, intraoperative blood loss, improvements in American Spinal Injury Association (ASIA) grading, and postoperative complications were recorded. The therapeutic efficacy was evaluated by comparisons of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), and Oswestry disability index (ODI) between preoperation, 2 weeks and 3 months postoperation, and the last follow-up.Results:Surgery went on successfully in all the 13 patients according to the preoperative planning. The surgical time was (275.9±28.3) min and the intraoperative blood loss (865.4±183.0) mL. All patients were followed up for (24.7±9.4) months. The levels of ESR, CRP, VAS, and ODI at 2 weeks, 3 months and the last follow-up were significantly lower than those before surgery ( P<0.05). At the last follow-up, X-ray and CT examinations showed good positions of internal fixation and sufficient bone graft fusion. The ASIA grading recovered from preoperative D to E in 5 patients. No incision infection, sinus formation, worsening of neurological symptoms, loosening or rupture of internal fixation, or worsening of neurological dysfunction were found. Conclusion:With the assistance of 3D visualization, the spinal cord, bone cement, and debridement area can be visualized directly to reduce nerve injury complications so that a safe and effective preoperative planning can be made for surgical clearance of vertebral infection lesions following PVP.

Objective:To assess the association between the polymorphisms of integral protein α4 ( ITGA4) and intercellular adhesion molecule 1 ( ICAM-1) genesand the risk and clinicopathological characteristics of Crohn′s disease (CD) among Chinese patients. Methods:From January 2010 to January 2021, a total of 215 CD patients and 529 gender- and age-matched healthy controls were enrolled from the Second Affiliated Hospital of Wenzhou Medical University as the study subjects. Genotypes of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) were determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Harvey-Bradshaw Index (HBI) was applied to assess the disease activity of CD, and the patients were further divided into subgroups based on the Montreal Classification Criteria of CD. Unconditional logistic regression was employed to analyze the distribution of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) polymorphisms between the patients and healthy controls and their association with the clinicopathological characteristics of the patients. Results:The frequencies of T allele and CT+ TT genotypes of ITGA4 (rs7562325) were higher in CD patients than the healthy controls (40.70% vs. 31.57%, P=0.001; 62.79% vs. 54.36%, P=0.042). The G variant and AG+ GG genotypes of ITGA4 (rs6740847) were less common in patients with moderately to severely active CD compared with those with mildly active CD (31.18% vs. 51.72%, P=0.002; 55.91% vs. 75.86%, P=0.042). However, the opposite conclusion was drawn for the G allele (G) and AG+ GG genotypes of ICAM-1 (rs5498) (31.45% vs. 17.24%, P=0.027; 54.30% vs. 31.04%, P=0.020). Compared with patients with terminal ileal or ileocolic CD, G allele and AG+ GG genotypes of ITGA4 (rs6740847) were more prevalent in patients with colonic CD (55.26% vs. 29.38%, P<0.000 1; 84.21% vs. 53.11%, P<0.000 1). The same conclusion could also be drawn for the G allele and AG+ GG genotypes of ICAM-1 (rs5498) (42.11% vs. 26.84%, P=0.008; 73.69% vs. 46.33%, P=0.002). The frequency of homozygous GG genotype of ICAM-1 (rs5498) was lower in patients with stricturing and penetrating CD than those with non-stricturing and non-penetrating CD (0.00% vs. 12.32%, P=0.001). The G allele and AG+ GG genotypes of the ITGA4 (rs6740847) were more common in patients with perianal lesions than those without (40.28% vs. 30.77%, P=0.049; 72.22% vs. 51.75%, P=0.004). Conclusion:Variants of the ITGA4 (rs7562325) may be a risk factor for CD, whilst those of the ITGA4 (rs6740847) may be associated with the decline of disease activity and risk for colon involvement and perianal lesions. Variants of the ICAM-1 (rs5498) may increase the risk of disease activity and colonic involvement in CD patients, however, it may be a protective factor for stenosis and penetration. In addition, variants of the ITGA4 (rs6740847) and ICAM-1 (rs5498) may be associated with the early onset of CD.

Objective:To explore the relationship between gene polymorphisms of integral protein alpha-4 ( ITGA4) and intercellular adhesion molecule-1 ( ICAM-1) and the risk of ulcerative colitis (UC), and to analyze the effects of ITGA4 and ICAM-1 gene variations on the clinical response of vedolizumab (VDZ) treatment in UC patients at week-14. Methods:From January 1, 2010 to January 31, 2023, at Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University, a total of 500 UC patients (UC group) and 529 gender- and age-matched healthy controls (healthy control group) were collected. The 500 UC patients were divided into mildly active stage (264 cases) and moderately to severely active stage (236 cases); distal colitis (299 cases), extensive colitis (201 cases); of the 500 UC patients, 120 cases received VDZ treatment, and 78 cases achieved clinical response and the remaining 42 cases had no response at week-14. Chi-square test and unconditional logistic regressionmodel were used to analyze the difference in gene polymorphisms of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene polymorphisms between UC group and healthy control group, between patients of mildly active stage and patients of moderately to severely active stage, between patients with distal colitis and patients with extensive colitis, between patients with clinical response and patients without response through dominant, recessive, and allelic gene models. Results:The results of dominant gene model analysis showed that, the frequency of the variant allele G and the variant genotype AG+ GG of ITGA4 rs6740847 of UC group were lower than those of healthy control group (28.60% vs. 33.18%, 48.00%vs. 56.15%), the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 of UC group were higher than those of healthy control group (37.30% vs.31.57%, 62.20% vs. 54.63%), and the differences were statistically significant( χ2=5.04, 6.83, 7.49 and 6.06, P=0.025, 0.009, 0.006 and 0.014); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with moderate to severe active UC were lower than those of patients with mild active UC (25.42% vs. 31.44%, 43.22% vs. 52.27%), while the frequency of variant allele T and variant genotype CT+ TT of ITGA4 rs7562325 were both higher than those of mild active UC (40.89% vs. 34.09%, 66.95% vs. 57.96%), and the differences were statistically significant( χ2=4.42, 4.09, 4.93 and 4.29, P=0.036, 0.043, 0.026 and 0.038); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847, the variant allele T of ITGA4 rs7562325, and the variant allele G and variant genotype AG+ GG of ICAM-1 rs5498 of patients with extensive colitis UC were lower than those of patients with distal colitis UC (24.38% vs. 31.44%, 39.80% vs. 53.51%, 33.58% vs.39.80%, 19.65% vs.26.09%, 35.82% vs. 45.82%), and the differences were statistically significant( χ2=5.87, 9.05, 3.97, 5.54 and 4.94, P=0.015, 0.003, 0.046, 0.019 and 0.026); the frequency of variant allele G and variant genotype AG+ GG of ITGA4 rs6740847 of patients with clinical response were higher than those of patients without response (34.62% vs.21.43%, 61.54% vs. 33.33%), and the differences were statistically significant( χ2=4.52 and 8.70, P=0.039 and 0.001). The results of recessive gene model analysis showed that, the frequency of variant genotype TT of ITGA4 rs7562325 of UC group was higher than that of healthy control group (12.40% vs.8.51%), and the difference was statistically significant ( χ2=4.18, P=0.041); the frequency of variant allele G and variant genotype GG of ICAM-1 rs5498 of patients with moderate to severe active UC were higher than those of patients with mild active UC (27.33% vs. 20.08%, 8.47% vs. 2.27%), and the differences were statistically significant( χ2=7.30 and 9.72, P=0.007 and 0.002); the frequency of variant allele T and variant genotype TT of ITGA4 rs7562325 of patients with clinical response were lower than those of patients without response (32.05% vs. 45.24%, 10.26% vs. 23.81%), and the differences were statistically significant( χ2=4.09 and 3.93, P=0.043 and 0.047). Conclusions:The variation of ITGA4 rs6740847 gene may reduce the risk and disease activity of UC, and may increase the clinical response to VDZ treatment in UC patients. However, the variation of ITGA4 rs7562325 gene may increase the risk and disease activity of UC, and may reduce the clinical response to VDZ treatment in UC patients. The variation of ICAM-1 rs5498 gene may worsen the disease activity of UC. In addition, the variations of ITGA4 rs6740847, rs7562325 and ICAM-1 rs5498 gene may all reduce the risk of extensive colitis.

Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.

Objective:To retrospectively analyze the effects of vitamin D3 supplementation on clinical remission of patients with Crohn′s disease (CD) in the treatment of infliximab (IFX).Methods:From January 2014 to January 2020, 73 patients with initial moderate to severe CD (50 patients with vitamin D deficiency (the level of serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/L)) receiving IFX treatment at Department of Gastroenterology were screened from the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. Harvey-Bradshaw index (HBI) was applied to evaluate the disease activity of CD patients. All the patients underwent IFX treatment (5 mg/kg) for at least 54 weeks. According to whether vitamin D3 (125 U/d) was supplemented during IFX treatment, the patients were divided into supplemented group ( n=37) and non-supplemented group ( n=36). In supplemented group, the level of 25(OH) D of patients at the 54th week was compared with that before IFX treatment. At the 54th week, the clinical remission rate and decline range of HBI were compared between supplemented group and non-supplemented group. And the influencing factors of clinical remission rate were analyzed in CD patients. Paired t test, independent sample t test, chi-square test and multivariable logistic regression were used for statistical analysis. Results:In supplemented group, the level of serum 25(OH)D at the 54th week was higher than that before IFX treatment ((50.83±15.45) nmol/L vs. (37.68±16.75) nmol/L), and the difference was statistically significant ( t=-4.55, P<0.001). At the 54th week, the clinical remission rate of supplemented group was higher than that of non-supplemented group (83.8%, 31/37 vs. 61.1%, 22/36), the decline range of HBI was larger than that of non-supplemented group (7.41±3.00 vs. 6.28±2.75), and the differences were statistically significant ( χ2=4.71, t=2.41; P=0.030 and 0.023). The results of multivariable logistic regression analysis showed that vitamin D3 supplementation was an independent factor affecting the clinical remission rate in CD patients ( n=73) and the patients with vitamin D deficiency ( n=50) ( b= -1.67 and -1.92 , P=0.015 and 0.019). Conclusions:Vitamin D3 supplementation can significantly improve the clinical remission rate in CD patients with IFX treatment, especially in CD patients with vitamin D deficiency.

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.

Objective:To investigate the relationship between polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 ( CDKN2 B- AS1) gene and the risk of ulcerative colitis (UC). Methods:From January 2012 to January 2021, a total of 534 UC patients diagnosed at the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University (Yuying Children′s Hospital) and during the same period 560 gender- and age-matched healthy controls were selected. Genotypes of CDKN2 B- AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) in venous blood were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression was used to analyze the difference in the distribution of CDKN2 B- AS1 gene polymorphisms between UC patients and healthy controls, as well as the influence on the clinicopathologic characteristics of UC patients. Software Haploview 4.2 was used to analyze the linkage disequilibrium and haplotype. Chi-square test was used for statistical analysis. Results:The frequencies of variant genotype (AG+ GG) and variant allele (G) of rs1063192 in UC patients were higher than those in healthy controls (32.4%, 173/534 vs. 24.8%, 139/560; 18.1%, 193/1 068 vs. 13.7%, 153/1 120), and the differences were statistically significant ( OR=1.45 and 1.40, 95% confidence interval(95% CI) 1.12 to 1.89 and 1.11 to 1.77, P=0.006 and 0.004, corrected P=0.030 and 0.020). The frequency of variant allele (G) of rs10757274 in UC patients was lower than that in healthy controls (34.7%, 371/1 068 vs. 39.5%, 442/1 120), and the difference was statistically significant ( OR=0.82, 95% CI 0.69 to 0.98, P=0.025). However, the difference was not significant after Bonferroni correction (corrected P>0.05). According to the Montreal classification, the frequency of homozygous variant genotype (GG) of rs1063192 in the patients with extensive colitis was higher than that in patients with proctitis plus left-sided colitis (6.6%, 14/211 vs. 1.9%, 6/323), and the difference was statistically significant ( OR=3.92, 95% CI 1.47 to 10.42, P=0.006, corrected P=0.030). There was linkage disequilibrium among rs10757274, rs2383207, rs10757278 and rs1333048 of CDKN2 B- AS1 gene. The frequency of haplotype GGGC in UC patients was lower than that in healthy controls (33.3%, 355.5/1 068 vs. 37.8%, 423.4/1 120), and the frequency of haplotype AGGC in UC patients was higher than that in healthy controls (6.7%, 71.7/1 068 vs. 3.6%, 40.3/1 120), and the differences were statistically significant ( χ2=4.81 and 11.16, P=0.028 and<0.001). Conclusions:The variation of rs1063192 in CDKN2 B- AS1 gene may increase the risk of UC. The risk of extensive colitis in patients carrying homozygous variant genotype (GG) of rs1063192 may rise. Among the haplotypes composed of rs10757274, rs2383207, rs10757278 and rs1333048, the risk of UC may decrease in the individuals carrying haplotype GGGC. However, the risk of UC may increase in the individuals carrying haplotype AGGC. The correlation between the variation of 10757274 and the risk of UC still needs to be further verified by expanding the sample size.

OBJECTIVE：To provide reference for furthe r promoting the high-quality development of the biomedical industry in Guangdong-Hong Kong-Macao Greater Bay Area. METHODS ：Through summarizing the development status and development environment of the biomedical industry in the Guangdong-Hong Kong-Macao Greater Bay Area ，the construction experience of foreign advanced biomedical industrial park was introduced ，and the problems and challenges faced by the biomedical industry in the Guangdong-Hong Kong-Macao Greater Bay Area were sorted out so as to put forward relevant countermeasures and suggestions. RESULTS & CONCLUSIONS ：Guangdong-Hong Kong-Macao Greater Bay Area has received multiple policy support，which is conducive to the development of biomedical industry. The industrial chain is complete ，and the scale advantage of biological industry is showing day by day. Biological industry has achieved fruitful innovation achievement ，and its R&D investment is in the leading position in the country. The pharmaceutical manufacturing industry is developed and the total amount of medical resources is large. The financial advantages are obvious ，and institutional innovation is conducive to the development of biomedical industry. The process of internationalization takes the leading place ，which is conducive to continuously promoting foreign cooperation. However ，compared with foreign advanced biomedical industrial parks ，Guangdong-Hong Kong-Macao Greater Bay Area still has some deficiencies in management mode ，service mode and “industry-university-institute”cooperation. It also faces the following problems that the legal systems and industry norms of the three places need to be further connected ；there is a talent gap ；the industrial chain is not perfect ；the support for new drug R&D is insufficient ；the“industry-university-institute” cooperation needs to be strengthened ；the level of financial support needs to be improved. Accordingly ，it is recommended to break down institutional barriers ，and promote the connection between the legal system and industry norms ；innovate talent policies ，and continue to attract excellent R&D talents ；introduce leading companies ，and improve the industrial chain ；open up clinical trial channels and promote the transformation efficiency of scientific research achievements ；strengthen“industry-university-institute” cooperation，and promote the improvement of biomedical innovation ability ；make good use of financial support to help the rapid rise of biomedical industry enterprises ，so as to promote the high-quality development of biomedical industry in Guangdong-Hong Kong-Macao Greater Bay Area.

Objective:To explore the application and value of metagenomic next-generation sequencing (mNGS) in refractory infection after organ transplantation.Methods:A case report discussed about a patient with lumbar spine infection after kidney transplantation and the relevant literature was reviewed. The recipient was a 63-year-old man with low back pain after kidney transplantation. Lumbar spine magnetic resonance imaging showed lumbar spine infection. Multiple operations plus antibacterial and antituberculosis treatments were ineffective. Before and after treatment, numerous tests of traditional pathogenic microorganisms failed to detect any positive bacteria.Results:The detection of lumbar secretion by mNGS suggested aspergillus infection. The symptoms improved after dosing of voriconazole.Conclusions:The incidence of fungal infection of lumbar spine is low. The imaging manifestations are non-typical so that it is easy to misdiagnose. mNGS helps to timely diagnose and guide treatment. With a review of the literature, mNGS has some application value for some difficult and rare infectious diseases.