Rectal cancer is one of the most common gastrointestinal malignant tumors,and patients with early rectal cancer can achieve radical tumor resection by surgical treatment alone,while most patients with rectal cancer are in the locally advanced stage when admitted to hospital.For this group of people,it is difficult to obtain a good prognosis through surgical treatment alone,and interventional chemoradio-therapy before surgery is of important clinical significance.A large number of clinical studies have proved that preoperative neoadjuvant therapy can effectively reduce tumor stage,increase pathological complete response(pCR)rate,thereby greatly improving the prognosis of patients.At present,the core methods of neoadjuvant therapy for locally advanced rectal cancer are radiotherapy and chemotherapy,as well as the emerging targeted therapy and immunotherapy,while the optimal combination order of various treatments remains in dispute.This article summarizes various neoadjuvant therapy regimens in recent years,in order to provide evidence for the multidisciplinary and comprehensive treatment of rectal cancer.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.

Rectal cancer is one of the most common gastrointestinal malignant tumors,and patients with early rectal cancer can achieve radical tumor resection by surgical treatment alone,while most patients with rectal cancer are in the locally advanced stage when admitted to hospital.For this group of people,it is difficult to obtain a good prognosis through surgical treatment alone,and interventional chemoradio-therapy before surgery is of important clinical significance.A large number of clinical studies have proved that preoperative neoadjuvant therapy can effectively reduce tumor stage,increase pathological complete response(pCR)rate,thereby greatly improving the prognosis of patients.At present,the core methods of neoadjuvant therapy for locally advanced rectal cancer are radiotherapy and chemotherapy,as well as the emerging targeted therapy and immunotherapy,while the optimal combination order of various treatments remains in dispute.This article summarizes various neoadjuvant therapy regimens in recent years,in order to provide evidence for the multidisciplinary and comprehensive treatment of rectal cancer.

Objective To investigate and analyze the distribution of serum cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma-associated antigen(SCCA)levels in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.Methods A total of 441 healthy pregnant women and 69 patients with cervical cancer in pregnancy who attended the Obstetrics and Gynecology Hospital of Fudan University from Jan 2021 to May 2024 were selected,and 165 healthy women in the Physical Examination Center of the Obstetrics and Gynecology Hospital of Fudan University were included in the same period as the control group.The healthy pregnant women were divided into 143 in early pregnancy(T1 group),147 in middle pregnancy(T2)and 151 in late pregnancy(T3).Serum CYFRA21-1 and SCCA values were detected and analyzed in all groups.One-way ANOVA,independent samples t-test,Mann-Whitney U-test,Kruskal-Wallis H-test,logistic analysis,and ROC curves were used for comparative analysis.Results The CYFRA21-1 and SCCA values were 1.66(1.19-2.17)ng/mL and 0.8(0.6-1.0)ng/mL in the control group,3.07(2.11-4.14)ng/mL and 0.9(0.7-1.3)ng/mL in the healthy pregnant women group,and were 4.33(2.99-7.60)ng/mL and 1.8(0.9-8.5)ng/mL in the patients with cervical cancer in pregnancy group,respectively.There was a statistically significant difference in the two serum values between every two groups(P<0.05).CYFRA21-1 levels were 3.13(2.46-4.05)ng/mL,1.89(1.50-2.53)ng/mL and 4.19(3.48-5.43)ng/mL in the T1,T2,and T3 groups,respectively;and SCCA levels were 0.9(0.7-1.1)ng/mL,0.7(0.6-1.0)ng/mL and 1.2(0.8-1.7)ng/mL,respectively.The results of T1 and T3 groups were higher than those of the control group(P<0.05);however,there was no statistically significant difference between the results of the T2 group and those of the control group(P>0.05).The areas under the ROC curves for the diagnosis of cervical cancer in pregnancy for CYFRA21-1,SCCA,human epididymis protein 4(HE4),anti-carcinoembryonic antigen(CEA)and joint indicators were 0.684,0.724,0.612,0.791 and 0.913,with sensitivities of 36%,48%,38%,57%and 73%,specificities of 96%,97%,89%,86%and 99%,respectively.The cut-off values of each indicator were 6.05 ng/mL,2.60 ng/mL,51.45 pg/mL and 1.75 ng/mL,respectively.Conclusion Serum CYFRA21-1 and SCCA levels were higher in pregnant women during early and late pregnancy compared with non-pregnant individuals,while they were not statistically different from non-pregnant women during mid-trimester.CYFRA21-1 and SCCA have diagnostic value for patients with cervical cancer during pregnancy.

Strong cation exchange mediums have been widely applied in protein purification.In this work,the strong cation exchange chromatography medium was prepared by coupling small molecular ligands through allyl activation commonly used in agarose-based media.The matrix based on the macroporous microspheres was a copolymer of glycidyl methacrylate and ethylene glycol dimethacrylate.The effects of reaction factors on the ligand density were detailedly investigated.The ligand density in the prepared medium was controlled in the range of 0.126-0.370 mol/L(wet gel).Its adsorption performance was evaluated with lysozyme as a model protein.The static binding capacity was in the range of 37.0-81.0 g/L.The maxium dynamic binding capacity reached 37.7 g/L and the maximum lysozyme recovery was 98.97%.The strong cation exchange medium obtained here showed low non-specific adsorption and high separation efficiency on lysozyme.This strong cation exchange medium showed a great potential in rapid protein purification.

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), β-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) μmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) μmol·L~(-1)].
Anti-Bacterial Agents ; Candida albicans ; China ; Liliaceae ; Melanthiaceae ; Rhizome

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q₁, Q₃) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q₁, Q₃) of 42 (20, 55) and the median exposure period (Q₁, Q₃) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
Male ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology* ; Incidence ; Family Characteristics