OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.

Objective:To compare the efficacy of robot-assisted percutaneous reduction and screw fixation versus open reduction and plate fixation via the sinus tarsi approach in the treatment of Sanders types II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 82 patients (90 feet) with calcaneal fractures admitted to the Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University from January 2020 to April 2024, including 74 males and 8 females, aged 24-87 years [(46.4±12.1)years]. According to Essex-Lopresti classification, the fractures were classified as tongue-type in 43 patients and joint-collapse-type in 47. According to Sanders classification, 69 feet were classified as type II and 21 as type III. Forty-seven patients (52 feet) were treated with robot-assisted percutaneous reduction and screw fixation (screw fixation group) and 35 (38 feet) with open reduction and plate fixation via the sinus tarsi approach (plate fixation group). The two groups were compared in terms of the operation duration, intraoperative blood loss, length of hospital stay and time to weight-bearing. The width, height, length, B?hler angle and Gissane angle of the calcaneus before surgery and at 1 day after surgery were compared. The Maryland foot and ankle function score, American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot function score, and visual analogue scale (VAS) score at 1, 3 months postoperatively, and at the last follow-up were compared. The incidence of postoperative complications and removal rate of internal fixation were also detected in the two groups.Results:All the patients were followed up for 9-60 months [(30.0±14.5)months]. There was no significant difference in the operation duration between the two groups ( P>0.05). The intraoperative blood loss, length of hospital stay and time to weight-bearing in the screw fixation group were 10.0(10.0, 20.0)ml, 7.0(5.0, 8.0)days and (5.0±0.8)weeks, which were significantly less or shorter than 30.0(20.0, 50.0)ml, 8.0(6.0, 11.0)days and (6.9±0.7)weeks in the plate fixation group ( P<0.05). The width, height, length, B?hler angle and Gissane angle of the calcaneus at 1 day after surgery were (43.4±4.2)mm, (46.2±4.0)mm, (81.6±5.1)mm, 27.1(20.4, 30.4)° and (113.4±10.1)° in the screw fixation group, which were all improved compared with those before surgery [(47.8±4.6)mm, (39.3±4.8)mm, (79.2±5.9)mm, 9.5(0.0,16.5)° and (119.3±13.4)°] ( P<0.01). The width, height, length and B?hler angle of the calcaneus at 1 day after surgery were (41.6±5.7)mm, (48.4±4.8)mm, (83.1±5.7)mm and 27.3(21.3, 31.6)° in the plate fixation group, which were all improved compared with those before surgery [(47.8±5.0)mm, (41.7±5.1)mm, (80.1±5.9)mm and 12.9(7.2,19.8)°] ( P<0.01), with no significant difference in the Gissane angle ( P>0.05). Before surgery and at 1 day postoperatively, no significant differences were found in the width, length, B?hler angle or Gissane angle of the calcaneus between the two groups ( P>0.05), while the height of the calcaneus in the screw fixation group was lower than that in the plate fixation group ( P<0.05). At 1 month after surgery and at the last follow-up, there were no significant differences in the Maryland foot and ankle function score, AOFAS ankle and hindfoot function score, and VAS score between the two groups ( P>0.05). At 3 months after surgery in the screw fixation group, the Maryland foot and ankle function score was (79.7±3.8)points, significantly higher than (74.7±2.8)points in the plate fixation group ( P<0.01); the AOFAS ankle and hindfoot function score was (77.1±5.0)points, significantly higher than (70.1±3.6)points in the plate fixation group ( P<0.01); the VAS score was 1.0(1.0, 2.0)points, significantly lower than 2.5(2.0, 3.0)points in the plate fixation group ( P<0.01). No significant difference was detected in the incidence of postoperative complications between the two groups ( P>0.05). The removal rate of internal fixation was 10% (5/52) in the screw fixation group, significantly lower than 29% (11/38) in the plate fixation group ( P<0.05). Conclusion:Compared with open reduction and plate fixation via the sinus tarsi approach, robot-assisted percutaneous reduction and screw fixation has the advantages of less intraoperative blood loss, shorter hospital stay, earlier weight-bearing exercises, better early functional recovery and pain relief, and lower internal fixation removal rate in the treatment of Sanders types II and III calcaneal fractures.

Objective:To investigate the therapeutic efficacy of different modes of neoadjuvant therapy for locally advanced rectal cancer (LARC) with proficient in mismatch repair intact (pMMR) or microsatellite stability (MSS).Methods:A retrospective case series study was conducted. A total of 210 LARC patients with pMMR or MSS admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were selected. Patients were divided into the chemotherapy alone group (98 cases) and the total neoadjuvant therapy (TNT) group (112 cases) based on different neoadjuvant treatment modes. The pathological complete remission (pCR) rate of both groups was compared. In the TNT group, 24 patients received short-course radiotherapy (SCRT) plus chemotherapy (group A), 62 patients received SCRT plus chemotherapy combined with immunotherapy (group B), 23 patients received long-course radiotherapy (LCRT) plus chemotherapy (group C), and 3 patients received LCRT plus chemotherapy combined with immunotherapy (group D). The pCR rate, tumor down-staging and the incidence of adverse reactions were compared between the 4 groups. A subgroup analysis was performed in 87 patients with the distance from the tumor site to anal verge >5 cm and T 2-3N 0-2M 0 TNM staging. And then 87 patients were divided into the chemotherapy alone group (47 cases) and the TNT group (40 cases), and the overall survival (OS) and disease-free survival (DFS) of patients were compared between the 2 groups. Results:Among the 210 LARC patients, 126 cases were male and 84 cases were female, with the age of (51±11) years. There were 3 cases in clinical stage Ⅱ and 207 cases in clinical stage Ⅲ; 68 cases with the distance from the tumor site to the anal verge <5 cm and 142 cases with the distance from the tumor site to the anal verge ≥ 5 cm. The pCR rate of the TNT group was higher than that of the chemotherapy alone group [40.2% (45/112) vs. 7.2% (7/98)], and the difference was statistically significant ( χ2 = 30.62, P < 0.001). In group D, 1 patient achieved pCR, but no statistical comparison was made due to the small sample size. There was no statistically significant difference in pCR rate between group A and group C [25.0% (6/24) vs. 21.7% (5/23), χ2 = 0.07, P = 0.792]. The pCR rate of group B was higher than that of group A and group C [53.2% (33/62) vs. 25.0% (6/24), 53.2% (33/62) vs. 21.7% (5/23)], and the differences were statistically significant ( χ2 = 5.56, P = 0.029; χ2 = 6.73, P = 0.013). However, there were no statistically significant differences in T and N down-staging among group A, group B and group C (all P > 0.05). During neoadjuvant treatment, the incidence of grade 3-4 myelosuppression was 10.7% (12/112) in the TNT group, and no grade 3-4 radiation proctitis was observed. The incidence of granulocytopenia in group B was lower than that in group A, and the incidence of thrombocytopenia in group was lower than that in group C; and the differences were statistically significant (all P < 0.05). In the subgroup analysis, there were no statistically significant differences in OS and DFS between the chemotherapy alone group and the TNT group ( χ2 = 2.17, P = 0.141; χ2 = 0.24, P = 0.624). Conclusions:The neoadjuvant treatment of SCRT combined with immunotherapy has a high pCR rate and a good safety in LARC patients with pMMR or MSS. TNT is not effective in improving the survival of low-risk LARC patients with tumors located in the mid to high segment of the rectum and may have the risk of overtreatment.

Objective To explore the effects and mechanism of calycosin-7-glucoside(CG)on lipopolysaccharide(LPS)-induced inflammatory injury in BV-2 cells and in a mouse model of neuroinflammation.Methods An in vitro neuroinflammation model was induced by LPS stimulation of BV-2 cells.BV-2 cells were divided into blank(CON),model(LPS),dexamethasone(DEX),and low-and high-dose CG(CG 10 μmol/L,CG 20 μmol/L,respectively)groups.The cell viability in each group was detected by Cell Counting Kit-8 assay,interleukin(IL)-6 and tumor necrosis factor(TNF)-α levels in the supernatant were detected by enzyme-linked immunosorbent assay(ELISA),and nitric oxide levels were detected using the Griess method.LPS was also used to induce neuroinflammation in mice in vivo.The mice were then divided randomly into blank(CON),model(LPS),aspirin,and low-and high-dose CG(CG 5 mg/kg,CG 10 mg/kg,respectively)groups.Pathological changes in the hippocampus were detected by hematoxylin/eosin staining.Serum levels of IL-6 and TNF-α were detected by ELISA,polarization of microglia was detected by immunofluorescence staining,and protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),nuclear factor κB(NF-κB,P65)and phosphorylated-NF-κB(p-P65)in the cortex were detected by Western blot.Results CG alone or in combination with LPS in the concentration range of 2.5～160 μmol/L had no significant toxicity in BV-2 cells in vitro,compared with the CON group(P＞0.05).IL-6,TNF-α,and NO levels in the cell supernatant were increased in the LPS group compared with the CON group(P＜0.01),but were significantly reduced by CG(P＜0.05,P＜0.01).Hippocampal neurons were arranged loosely and disordered in the LPS group in vivo,compared with the CON group,and nuclear pyknosis was observed.Serum levels of IL-6 and TNF-α were increased(P＜0.05,P＜0.01).The number of ionized calcium binding adaptor molecule 1(Iba1)/inducible nitric oxide synthase(iNOS)cells was increased(P＜0.01),the number of CD206/Iba1 cells was decreased(P＜0.01),and expression levels of TLR4,MyD88,and p-P65 protein in the cortex were increased(P＜0.05).Compared with the LPS group,CG improved the pathological damage to the hippocampus and inhibited serum levels of IL-6 and TNF-α(P＜0.01).CG also decreased the number of iNOS/Iba1 cells,increased the number of CD206/Iba1 cells(P＜0.05,P＜0.01),and significantly down-regulated TLR4,MyD88,and p-P65 protein levels in the cortex(P＜0.05).Conclusions CG can ameliorate neuroinflammation in mice by suppressing the TLR4/MyD88/NF-κB pathway.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.

Objective To explore the effects and mechanism of calycosin-7-glucoside(CG)on lipopolysaccharide(LPS)-induced inflammatory injury in BV-2 cells and in a mouse model of neuroinflammation.Methods An in vitro neuroinflammation model was induced by LPS stimulation of BV-2 cells.BV-2 cells were divided into blank(CON),model(LPS),dexamethasone(DEX),and low-and high-dose CG(CG 10 μmol/L,CG 20 μmol/L,respectively)groups.The cell viability in each group was detected by Cell Counting Kit-8 assay,interleukin(IL)-6 and tumor necrosis factor(TNF)-α levels in the supernatant were detected by enzyme-linked immunosorbent assay(ELISA),and nitric oxide levels were detected using the Griess method.LPS was also used to induce neuroinflammation in mice in vivo.The mice were then divided randomly into blank(CON),model(LPS),aspirin,and low-and high-dose CG(CG 5 mg/kg,CG 10 mg/kg,respectively)groups.Pathological changes in the hippocampus were detected by hematoxylin/eosin staining.Serum levels of IL-6 and TNF-α were detected by ELISA,polarization of microglia was detected by immunofluorescence staining,and protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),nuclear factor κB(NF-κB,P65)and phosphorylated-NF-κB(p-P65)in the cortex were detected by Western blot.Results CG alone or in combination with LPS in the concentration range of 2.5～160 μmol/L had no significant toxicity in BV-2 cells in vitro,compared with the CON group(P＞0.05).IL-6,TNF-α,and NO levels in the cell supernatant were increased in the LPS group compared with the CON group(P＜0.01),but were significantly reduced by CG(P＜0.05,P＜0.01).Hippocampal neurons were arranged loosely and disordered in the LPS group in vivo,compared with the CON group,and nuclear pyknosis was observed.Serum levels of IL-6 and TNF-α were increased(P＜0.05,P＜0.01).The number of ionized calcium binding adaptor molecule 1(Iba1)/inducible nitric oxide synthase(iNOS)cells was increased(P＜0.01),the number of CD206/Iba1 cells was decreased(P＜0.01),and expression levels of TLR4,MyD88,and p-P65 protein in the cortex were increased(P＜0.05).Compared with the LPS group,CG improved the pathological damage to the hippocampus and inhibited serum levels of IL-6 and TNF-α(P＜0.01).CG also decreased the number of iNOS/Iba1 cells,increased the number of CD206/Iba1 cells(P＜0.05,P＜0.01),and significantly down-regulated TLR4,MyD88,and p-P65 protein levels in the cortex(P＜0.05).Conclusions CG can ameliorate neuroinflammation in mice by suppressing the TLR4/MyD88/NF-κB pathway.

Objective:To compare the efficacy of robot-assisted percutaneous reduction and screw fixation versus open reduction and plate fixation via the sinus tarsi approach in the treatment of Sanders types II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 82 patients (90 feet) with calcaneal fractures admitted to the Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University from January 2020 to April 2024, including 74 males and 8 females, aged 24-87 years [(46.4±12.1)years]. According to Essex-Lopresti classification, the fractures were classified as tongue-type in 43 patients and joint-collapse-type in 47. According to Sanders classification, 69 feet were classified as type II and 21 as type III. Forty-seven patients (52 feet) were treated with robot-assisted percutaneous reduction and screw fixation (screw fixation group) and 35 (38 feet) with open reduction and plate fixation via the sinus tarsi approach (plate fixation group). The two groups were compared in terms of the operation duration, intraoperative blood loss, length of hospital stay and time to weight-bearing. The width, height, length, B?hler angle and Gissane angle of the calcaneus before surgery and at 1 day after surgery were compared. The Maryland foot and ankle function score, American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot function score, and visual analogue scale (VAS) score at 1, 3 months postoperatively, and at the last follow-up were compared. The incidence of postoperative complications and removal rate of internal fixation were also detected in the two groups.Results:All the patients were followed up for 9-60 months [(30.0±14.5)months]. There was no significant difference in the operation duration between the two groups ( P>0.05). The intraoperative blood loss, length of hospital stay and time to weight-bearing in the screw fixation group were 10.0(10.0, 20.0)ml, 7.0(5.0, 8.0)days and (5.0±0.8)weeks, which were significantly less or shorter than 30.0(20.0, 50.0)ml, 8.0(6.0, 11.0)days and (6.9±0.7)weeks in the plate fixation group ( P<0.05). The width, height, length, B?hler angle and Gissane angle of the calcaneus at 1 day after surgery were (43.4±4.2)mm, (46.2±4.0)mm, (81.6±5.1)mm, 27.1(20.4, 30.4)° and (113.4±10.1)° in the screw fixation group, which were all improved compared with those before surgery [(47.8±4.6)mm, (39.3±4.8)mm, (79.2±5.9)mm, 9.5(0.0,16.5)° and (119.3±13.4)°] ( P<0.01). The width, height, length and B?hler angle of the calcaneus at 1 day after surgery were (41.6±5.7)mm, (48.4±4.8)mm, (83.1±5.7)mm and 27.3(21.3, 31.6)° in the plate fixation group, which were all improved compared with those before surgery [(47.8±5.0)mm, (41.7±5.1)mm, (80.1±5.9)mm and 12.9(7.2,19.8)°] ( P<0.01), with no significant difference in the Gissane angle ( P>0.05). Before surgery and at 1 day postoperatively, no significant differences were found in the width, length, B?hler angle or Gissane angle of the calcaneus between the two groups ( P>0.05), while the height of the calcaneus in the screw fixation group was lower than that in the plate fixation group ( P<0.05). At 1 month after surgery and at the last follow-up, there were no significant differences in the Maryland foot and ankle function score, AOFAS ankle and hindfoot function score, and VAS score between the two groups ( P>0.05). At 3 months after surgery in the screw fixation group, the Maryland foot and ankle function score was (79.7±3.8)points, significantly higher than (74.7±2.8)points in the plate fixation group ( P<0.01); the AOFAS ankle and hindfoot function score was (77.1±5.0)points, significantly higher than (70.1±3.6)points in the plate fixation group ( P<0.01); the VAS score was 1.0(1.0, 2.0)points, significantly lower than 2.5(2.0, 3.0)points in the plate fixation group ( P<0.01). No significant difference was detected in the incidence of postoperative complications between the two groups ( P>0.05). The removal rate of internal fixation was 10% (5/52) in the screw fixation group, significantly lower than 29% (11/38) in the plate fixation group ( P<0.05). Conclusion:Compared with open reduction and plate fixation via the sinus tarsi approach, robot-assisted percutaneous reduction and screw fixation has the advantages of less intraoperative blood loss, shorter hospital stay, earlier weight-bearing exercises, better early functional recovery and pain relief, and lower internal fixation removal rate in the treatment of Sanders types II and III calcaneal fractures.

Objective:To investigate the therapeutic efficacy of different modes of neoadjuvant therapy for locally advanced rectal cancer (LARC) with proficient in mismatch repair intact (pMMR) or microsatellite stability (MSS).Methods:A retrospective case series study was conducted. A total of 210 LARC patients with pMMR or MSS admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were selected. Patients were divided into the chemotherapy alone group (98 cases) and the total neoadjuvant therapy (TNT) group (112 cases) based on different neoadjuvant treatment modes. The pathological complete remission (pCR) rate of both groups was compared. In the TNT group, 24 patients received short-course radiotherapy (SCRT) plus chemotherapy (group A), 62 patients received SCRT plus chemotherapy combined with immunotherapy (group B), 23 patients received long-course radiotherapy (LCRT) plus chemotherapy (group C), and 3 patients received LCRT plus chemotherapy combined with immunotherapy (group D). The pCR rate, tumor down-staging and the incidence of adverse reactions were compared between the 4 groups. A subgroup analysis was performed in 87 patients with the distance from the tumor site to anal verge >5 cm and T 2-3N 0-2M 0 TNM staging. And then 87 patients were divided into the chemotherapy alone group (47 cases) and the TNT group (40 cases), and the overall survival (OS) and disease-free survival (DFS) of patients were compared between the 2 groups. Results:Among the 210 LARC patients, 126 cases were male and 84 cases were female, with the age of (51±11) years. There were 3 cases in clinical stage Ⅱ and 207 cases in clinical stage Ⅲ; 68 cases with the distance from the tumor site to the anal verge <5 cm and 142 cases with the distance from the tumor site to the anal verge ≥ 5 cm. The pCR rate of the TNT group was higher than that of the chemotherapy alone group [40.2% (45/112) vs. 7.2% (7/98)], and the difference was statistically significant ( χ2 = 30.62, P < 0.001). In group D, 1 patient achieved pCR, but no statistical comparison was made due to the small sample size. There was no statistically significant difference in pCR rate between group A and group C [25.0% (6/24) vs. 21.7% (5/23), χ2 = 0.07, P = 0.792]. The pCR rate of group B was higher than that of group A and group C [53.2% (33/62) vs. 25.0% (6/24), 53.2% (33/62) vs. 21.7% (5/23)], and the differences were statistically significant ( χ2 = 5.56, P = 0.029; χ2 = 6.73, P = 0.013). However, there were no statistically significant differences in T and N down-staging among group A, group B and group C (all P > 0.05). During neoadjuvant treatment, the incidence of grade 3-4 myelosuppression was 10.7% (12/112) in the TNT group, and no grade 3-4 radiation proctitis was observed. The incidence of granulocytopenia in group B was lower than that in group A, and the incidence of thrombocytopenia in group was lower than that in group C; and the differences were statistically significant (all P < 0.05). In the subgroup analysis, there were no statistically significant differences in OS and DFS between the chemotherapy alone group and the TNT group ( χ2 = 2.17, P = 0.141; χ2 = 0.24, P = 0.624). Conclusions:The neoadjuvant treatment of SCRT combined with immunotherapy has a high pCR rate and a good safety in LARC patients with pMMR or MSS. TNT is not effective in improving the survival of low-risk LARC patients with tumors located in the mid to high segment of the rectum and may have the risk of overtreatment.

Objective Exploring the predictive value of amplitude integrated electroencephalography(aEEG)and brainstem auditory evoked potentials(BAEP)in cognitive and affective disorders related to cerebral small vessel disease(CSVD).Methods Retrospectively,100 patients with CSVD who visited the Department of Neurology at the Fourth Affiliated Hospital of Soochow University from January 2021 to February 2024 were included in the CSVD group.From January 2021 to February 2024,100 healthy people who underwent physical examination in the Physical Examination Center of the Fourth Affiliated Hospital of Soochow University and matched with the CSVD group for age and sex were prospectively included as the control group.Basic and clinical data were collected and compared between the CSVD group and the control group,including age,sex,years of education,hypertension,diabetes,smoking,drinking,total cholesterol,triglycerides,low-density lipoprotein cholesterol(LDL-C),C-reactive protein(CRP),galactin-3(Gal-3),cystatin C,homocysteine(Hcy),blood Tau protein,and glial fibrillary acidic protein(GFAP).Cognitive function was assessed using the mini-mental state examination(MMSE)and the Montreal cognitive assessment(MoCA)scale,with a MMSE score＜24 and a MoCA score＜25 indicating cognitive impairment.affective disorders were assessed using the Hamilton anxiety scale(HAMA)and the Hamilton depression scale(HAMD),with a HAMA score ≥ 14 or a HAMD score ≥20 indicating the presence of affective disorders.The scores of the above four scales were compared between the CSVD group and the control group.aEEG and BAEP data were collected and compared between the CSVD group and the control group.aEEG results were evaluated based on a composite score of background activity stability,sleep-wake cycle,lower boundary amplitude,and narrowband width,with a score of 0-3 indicating aEEG abnormalities.In the BAEP waveform,the Ⅰ,Ⅲ,and Ⅴ waves and the inter-wave intervals of Ⅰ-Ⅲ,Ⅲ-Ⅴ and Ⅰ-Ⅴ were observed and recorded,along with their peak latencies and inter-peak latencies.If the latency of each wave is prolonged＞mean+3 standard deviations and/or the interwave period is prolonged＞mean+3 standard deviations,it was considered a BAEP abnormality.CSVD patients were divided into cognitive impairment and non-cognitive impairment based on MMSE scale score and MoCA scale score,and all CSVD patients were divided into affective disorder and non-affective disorder based on HAMA score and HAMD score.The independent variables with statistically significant differences and no collinearity in the univariate analysis of cognitive and affective disorders in CSVD patients were included in the multivariate Logistic regression analysis,and the statistically significant factors were used to form the multivariate model.The area under the receiver operating characteristic(ROC)curve was used to analyze the predictive value of the multi-factor model for CSVD-related cognitive and affective disorders.Results(1)The proportion of hypertension patients,the levels of CRP,Gal-3,cystatin C,Hcy,Tau protein,GFAP,HAMA and HAMD scores in the CSVD group were higher than those in the control group(all P＜0.05),and the MMSE and MoCA scale were lower than those in the control group(both P＜0.05).The scores of continuity,sleep-wake cycle,lower boundary amplitude and narrow band width of aEEG in the CSVD group were lower than those in the control group(all P＜0.05).The peak latency and interpeak latency of BAEP in the CSVD group were higher than those in the control group(all P＜0.05).(2)There were 52 patients with cognitive impairment and 48 patients with non-cognitive impairment in CSVD patients.There were 36 patients with affective disorder and 64 patients with non-affective disorder.There were 17patients with both cognitive and affective disorders.The age,Tau protein,GFAP,the proportion of patients with abnormal aEEG and the proportion of patients with abnormal BAEP in patients with cognitive impairment were higher than those in patients without cognitive impairment(all P＜0.05).The age of patients with affective disorder,the proportion of patients with abnormal aEEG and the proportion of patients with abnormal BAEP were higher than those of patients without affective disorder(all P＜0.05).(3)Multivariate Logistic regression analysis showed that the risk of cognitive impairment in patients with abnormal aEEG CSVD was 4.364 times higher than that in patients with normal aEEG CSVD(OR,4.364,95％CI 1.554-12.252,P=0.005).The risk of cognitive impairment in patients with abnormal BAEP CSVD was 3.218 times higher than that in patients with normal BAEP CSVD(OR,3.218,95％CI 1.218-8.503,P=0.018).The ROC curve was used to analyze the predictive value of the multi-factor model jointly constructed by aEEG abnormalities and BAEP abnormalities for CSVD cognitive impairment.The results showed that the area under the ROC curve was 0.732,the sensitivity was 76.38％,and the specificity was 82.59％.(4)Multivariate Logistic regression analysis showed that the risk of affective disorder in patients with abnormal aEEG CSVD was 3.203 times higher than that in patients with normal aEEG CSVD(OR,3.203,95％CI 1.288-7.966,P=0.012).The risk of affective disorder in patients with abnormal BAEP CSVD was 2.553 times higher than that in patients with normal BAEP CSVD(OR,2.553,95％CI 1.011-6.446,P=0.047).The ROC curve was used to analyze the predictive value of the multi-factor model jointly constructed by aEEG abnormalities and BAEP abnormalities for CSVD affective disorders.The results showed that the area under the ROC curve was 0.700,the sensitivity was 74.21％,and the specificity was 83.49％.Conclusions The abnormality of aEEG and BAEP are important factors in constructing the prediction model of cognitive and affective disorders in CSVD patients.The multi-factor model constructed by aEEG and BAEP has certain value in predicting CSVD-related cognitive and affective disorders.