Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

Objective:To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors.Methods:A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups.Results:All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436–34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220–36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017–12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive ( n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion:In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.

Objective To study the changes in serum immunoglobulin levels in children with thalassemia who undergo repeated blood transfusions and explore their correlation with delayed hemolytic transfusion reactions(DHTR).Methods Serum samples from children with thalassemia who received blood transfusion treatment from June 2022 to April 2023(ob-servation group)and healthy children who underwent physical examination(control group)in our hospital were collected.The levels of serum immunoglobulins(IgG subtype,IgM,IgA,IgE and IgD)were detected using flow cytometry CBA multi-factor quantitative detection technology,and the differences between the two groups were compared.The children were divided into 4 groups according to different transfusion numbers:≤10 numbers,11-30 numbers,31-50 numbers and＞50 numbers,and the differences between different blood transfusion numbers and serum immunoglobulin levels in each group were compared using one-way analysis of variance(ANOVA).Children with thalassemia with DHTR were in the hemolysis group,and children with thalassemia who did not experience DHTR were in the non-hemolysis group.The changes in serum immunoglobulins(IgG subtypes,IgM,IgA,IgE and IgD)between the two groups were compared to explore the correlation between serum immunoglobulins in thalassemia children with repeated transfusion and DHTR.Results The levels of IgG1,IgG3,IgG4 and IgA in the observation group were significantly higher than those in the control group,with the increase of(2.07±2.12),(0.67±2.03),(0.30±0.37)and(6.04±11.40)mg/mL,respectively,while the level of IgD in observation group was significantly lower than that in the control group,with a decrease of(0.03±0.01)mg/mL,P＜0.05.No significant difference was noticed in IgG2,IgM and IgE between the groups(P＞0.05).IgG1 and IgG4 both significantly increased with the number of blood transfusions.The IgG1 in the 4 groups increased sequentially as(0.30±0.62),(0.41±0.51)and(3.60±3.48)mg/mL,and IgG4 increased sequentially as(0.12±0.13),(0.22±0.07)and(0.21±0.38)mg/mL.IgG2,IgM and IgD showed a significant decrease,with IgG 2,IgM,and IgD in four groups decreased as(0.91±1.50),(0.14±0.10)and(0.05±0.05)mg/mL,respectively,showing significant differences with the number of blood transfusions(P＜0.05).No sig-nificant difference was found in IgG3,IgA and IgE with different number of transfusions(P＞0.05).IgG1,IgG3 and IgG4 in the hemolysis group were significantly higher than those in the non-hemolysis group,with an increase of(4.44±3.41),(0.73±1.26)and(0.52±0.40),respectively(P＜0.05).IgD in the hemolysis group was significantly lower than that in the non-hemolysis group,with a decrease of(0.00±0.06)mg/mL,P＜0.05.No significance was noticed in IgG2,IgM,IgA and IgE between the hemolysis group and the non-hemolysis group(P＞0.05).Conclusion The serum immunoglobulin levels of children with thalassemia who undergo repeated blood transfusions are abnormal.There are differences in correlation between the number of blood transfusions and serum immunoglobulin levels among children with thalassemia who undergo repeated blood transfusions.The relevant serum immunoglobulins for DHTR in children with thalassemia who undergo repeated blood transfusions are IgG1,IgG3 and IgG4.

【Objective】 To investigate the changes in cellular immunity (peripheral blood lymphocyte subsets) and humoral immunity (serum immunoglobulin and ferritin) status among children with thalassemia who received repeated transfusions in Yunnan. 【Methods】 Forty-six children with thalassemia who underwent repeated blood transfusions from January 2020 to October 2022 were selected as the observation group. Forty children with thalassemia who did not receive blood transfusion were included in control group 1, and 46 healthy children underwent physical examination were included in control group 2. The differences in lymphocyte subsets, serum immunoglobulin levels and ferritin concentrations were compared among the three groups. 【Results】 For lymphocyte subsets: CD3⁺, CD4⁺ and CD4⁺/CD8⁺ in the observation group was lower than the control group 1 and 2: 57.60±8.36 vs 64.57±7.56 vs 66.58±5.65, 33.16±5.67 vs 38.62±8.36 vs 38.62±6.41 and 1.49±0.09 vs 2.32±0.15 vs 2.13±0.16, respectively; CD16⁺ CD56⁺ in the observation group was lower than the control group 2: 11.21±5.06 vs 16.70±7.92; CD8⁺ in the observation group was higher than control group 1 and control group 2: 26.63± 1.75 vs 20.60±1.43 vs 18.92±0.84; CD19⁺ in the observation group was higher than the control group 2: 24.06±6.42 vs 19.67 ±8.42, P<0.05, but no significant difference was noticed between the two control groups(P>0.05). For serum immunoglobulin and ferritin: IgG and ferritin in the observation group were higher than control group 1 and control group 2: 10.59±3.88 vs 7.02±3.88 vs 5.58±1.98 and 2 037.37±1 377.59 vs 72.63±56.71 vs 59.48±33.88. IgA in the observation group was higher than the control group 2: 1.06±0.92 vs 0.39±0.32(P<0.05), but no significant difference was noticed between the two control groups (P>0.05). The difference of IgM and IgE between the three groups was not significant (P > 0. 05). 【Conclusion】 The proportion of lymphocyte subsets in thalassemia children with repeated blood transfusion was imbalanced,and the level of immunoglobulin in humoral immunity was abnormal.

【Objective】 To share the experience of autologous platelet-rich plasma(PRP) combined therapy in successful treatment of refractory osteomyelitis with fractures in children. 【Methods】 One case of refractory osteomyelitis with fracture in children failed to respond to traditional treatment for more than 14 months. A total of 20 mL of whole blood was collected from the child, and 6 mL of PRP with 4 to 5 times concentration was prepared by secondary centrifugation. To prepare 2 cm×2 cm platelet concentrate gel (PG), 3 mL of PRP was mixed with a 0.3 mL activator which was then covered with an absorbable dressing. A three-way tube sprayed the remaining 3 mL of PRP and 0.3 mL activator into the surrounding tissues. 【Results】 The X-ray film of the patient followed up for 1 week showed that the fracture line was blurred, and the fracture end had obvious callus formation. The X-ray film reexamination at 4 months showed that the fracture end healed well, the fracture surface healed, and the osteomyelitis healed. 【Conclusion】 Autologous PRP has a good effect in the treatment of refractory osteomyelitis combined with fracture in children, which can provide a new method for clinical treatment.

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

Objective To investigate the mechanism of action of integrin α4 (ITGA4) in liver fibrosis based on the anti-liver fibrosis effect of sticky sugar amino acid (SSAA) in rats. Methods A rat model of liver fibrosis was induced by intraperitoneal injection of CCl 4 , and then colchicine and low-, middle-, and high-dose SSAA were used for intervention, with blank control group and SSAA group as control. After 12 weeks of experimental intervention, serum and liver samples were collected to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and HE staining and Sirius Red staining were used to observe the pathological conditions of liver tissue; quantitative real-time PCR was used to measure the transcriptional level of ITGA4, integrin β1 (ITGB1), transforming growth factor-β1 (TGFβ1), alpha-smooth muscle actin (α-SMA), and TIMP2 in liver tissue; Western blot was used to measure the relative protein expression levels of ITGA4, ITGB1, TGFβ1, α-SMA, MMP2, TIMP1, and TIMP2; immunohistochemistry was used to observe the protein expression of TGFβ1 and α-SMA. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for comparison between two groups. Results There were significant increases in AST and ALT in the CCl 4 model group, and intervention with colchicine or low-, middle-, and high-dose SSAA reduced the levels of AST and ALT, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). HE staining and Sirius Red staining showed disordered structure of hepatic lobules and an increase in collagen fibers in the CCl 4 model group, and the structure of hepatic lobules was improved after intervention with colchicine or low-, middle-, and high-dose SSAA. The CCl 4 model group had significantly higher transcriptional levels of ITGA4, TGFβ1, α-SMA, and TIMP2 than the other groups, and there were significant reductions in the transcriptional levels of each factor after intervention with colchicine or SSAA, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). The CCl 4 model group had significantly higher protein expression levels of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and a significantly lower protein expression level of MMP2 than the other groups, and intervention with colchicine or SSAA inhibited the expression of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and promoted the expression of MMP2. Immunohistochemistry showed that the CCl 4 model group had significantly higher expression levels of TGFβ1 and α-SMA than the other groups, which was inhibited by intervention with colchicine or SSAA. The high-dose SSAA group had the most significant effect in reducing aminotransferases, improving lobular structure, and inhibiting the protein expression of liver fibrosis factors. Conclusion The high expression of ITGA4 in the liver is associated with the development of liver fibrosis, which is consistent with the increases in the expression of TGFβ1 and α-SMA. Inhibiting the expression of ITGA4 can provide more therapeutic targets for liver fibrosis and expand the anti-liver fibrosis mechanism of SSAA.

【Objective】 To study the yielding rate and distribution of unexpected antibodies in blood transfusion children with thalassemia in Yunnan province, and to explore the blood transfusion strategies. 【Methods】 From January 2016 to December 2021, 298 children with thalassemia, who received blood transfusion treatment in Kunming, Xishuangbanna, Wenshan, Dehong, Yuxi and Baoshan hospitals across Yunnan Province, were selected. The unexpected antibodies of blood plasma were screened by microcolumn gel card. The samples with positive antibodies were identified for alloantibody specificity. 【Results】 Unexpected antibodies were yielded in 67 out of 298(22.48%) transfused children with thalassemia. The positive rates of unexpected antibodies in boys and girls were 16.55%(24/145) and 28.10%(43/153), respectively. The positive rates of unexpected antibodies in Han, Dai, Zhuang, Yi, Bulang, Jinuo and Miao people were 14.06%(18/128), 30.80%(32/104), 35.71%(10/28), 36.36%(8/22), 50.00%(4/8), 60.00%(3/5)and 66.67%(2/3), respectively, with statistically significant differences between each other. The positive rate of unexpected antibodies in ethnic minorities was higher than that in Han. The positive rates of unexpected antibodies in children who received the first transfusion at birth-one year old, 1~3 years old, 3~6 years old and above 6 years old were 12.50%(3/24), 10.14%(7/69), 24.54%(40/163)and 40.48%(17/42), respectively. The positive rates of unexpected antibodies in children with first transfusion after 3 years old were significantly higher than those before 3 years old. The positive rates of unexpected antibodies in children with one transfusion, 1~3, 3~10, 10~20 and more than 20 transfusions were 4.76%(1/21), 12.07%(7/58), 23.71%(23/97), 28.16%(29/103)and 36.84%(7/19), respectively, with statistically significant differences between each other. The number of blood transfusions was positively correlated with the unexpected antibody yielding. The yielding rate of unexpected antibodies in children with α thalassemia, βthalassemia, δ+ βthalassemia and untyped thalassemia was 7.50%(3/40), 17.62%(34/193), 53.70%(29/54)and 9.09%(1/11), respectively(P<0.05). The yielding rate of unexpected antibodies in transfused children with δ+ βthalassemia was the highest. And 57 unexpected antibodies of Rh blood group system were yielded, 6 anti-M antibodies, 2 anti-N antibodies and 2 undetermined. 【Conclusion】 The positive rate of unexpected antibodies in transfused children with thalassemia in Yunnan province is high. Routine antibody screening should be carried out for transfusion children with thalassemia, and blood units, compatible with ABO, Rh and MNS typing results, should be selected to ensure the safety and effectiveness of clinical blood use.

Objective:To investigate the effects of different doses of dexmedetomidine combined with tramadol on intravenous analgesia and sleep quality after cesarean section.Methods:One hundred and twenty pregnant women who underwent cesarean section in Zhongshan Boai Hospital from March 2019 to July 2020 were selected. They were randomly divided into four groups, with 30 patients in each group. The patients in group Awere given patient controlled anesthesia with tramadol 800 mg+ tropisetron 5mg after cesarean section, and the patients in group B1, B2 and B3 were given 1.0, 1.5, 2.0 μg/kg dexmedetomidine on the basis of group A. The scores of exercise and rest of visual analogue scale (VAS) at 6, 12, 24 and 48 h after the surgery were observed. The scores of Athens insomnia scale (AIS) before and after surgery were compared. The Ramsay sedation scores and basic vital signs were recorded, compared and analyzed at 6, 12, 24 and 48 h after the surgery. The incidence of adverse reactions within 48 h after the surgery was counted in the four groups.Results:The scores of exercise and rest of VAS at 6, 12, 24 and 48 h after the surgery in four groups had significant differences ( P<0.05). The scores of group A were the highest, and next were the group B1, B2 and B3. The scores of AIS at 1 and 2 d after surgery in four groups had significant differences ( P<0.05).The scores of group A were the highest, and next were the group B1, B2 and B3.The level of oxyhemoglobin saturation (SpO 2) after surgery in four groups had no significant difference ( P>0.05). The levels of systolicblood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) after surgery in four groups had significant differences ( P<0.05). The levels of SBP, DBP, HR in group A were the highest, and next were the group B1, B2 and B3. Thelevels of SBP, DBP, HR in group A, B1 and B2 were in normal range, but the levels of SBP, DBP and HR in group B3 were in lower limits of normal, the level of HR in some patients was below normal. The Ramsay sedation scores at 6, 12, 24 and 48 h after surgery in the four groups had significant differences ( P<0.05). Ramsay sedation scores in group A were the lowest, and next were the group B1, B2 and B3. The total incidence of adverse reactions in group B3 was the highest with 33.33%(10/30), and in group B1 was the lowest with 6.67%(2/30). Conclusions:Medium dose of dexmedetomidine (1.5 μg/kg) combined with tramadol has a good effect on postoperative intravenous sedation and analgesia in patients after cesarean section, which can improve the sleep quality of patients. Besides, the drug safety can be guaranteed.

【Objective】 To analyze the effect of intravenous immunoglobulin(IVIG)-produced IgG antibody on the crossmatch incompatibility of neonates. 【Methods】 Blood type grouping, antibody screening, crossmatch, direct anti-globulin test, elution test, indirect antiglobulin test, and IVIG titer determination were conducted by microcolumn gel method. 【Results】 IgG anti-A were detected out in the elution test and free antibody test of 6 infants, and the titer of IgG anti-A contained in IVIG was 256, which led to the crossmatch incompatibility between infants and donors with the same type. 【Conclusion】 The hemolysis and crossmatch incompatibility in newborns, born to ABO-compatible mothers, may occur due to the IVIG-induced IgG antibodies. The O-type washed red blood cells should be selected for transfusion.