Objective:To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR).Methods:This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded.Results:None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0–300.0) minutes, 240.0 (225.0–270.0) minutes and 270.0 (240.0–356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7–12.7; OR=2.6, 95%CI: 1.0–6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0–12.0) days, 10.0 (8.0–17.0) days and 11.5 (9.0–19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5–8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ 2=4.133, P=0.023). Conclusions:In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Objective:To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR).Methods:This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded.Results:None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0–300.0) minutes, 240.0 (225.0–270.0) minutes and 270.0 (240.0–356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7–12.7; OR=2.6, 95%CI: 1.0–6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0–12.0) days, 10.0 (8.0–17.0) days and 11.5 (9.0–19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5–8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ 2=4.133, P=0.023). Conclusions:In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

We report a case of a long-term survivor of heart transplant who developed severe COVID-19 and was treated with a traditional Chinese medicine combined with conventional medicine. Throughout the treatment， the patient received active conventional medical treatment， and traditional Chinese medicine interventions included tonifying qi， invigorating the spleen and transforming phlegm， promoting yang and eliminating stagnation， resolving dampness and dissipating phlegm， and promoting blood circulation and eliminating stasis. The main therapeutic principles adopted were to recuperating depleted yang and rescuing the patient from collapse and to resolve phlegm and promote water. Pogezilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications was administered. In summary， it is crucial to the timely adjust the immunosuppressive regimen， combine use of various anti-infective agents with a focus on COVID-19， to protect of cardiac and renal function， and to integrate traditional Chinese medicine in the entire treatment process. As this case is rare， the diagnostic and therapeutic methods in traditional Chinese medicine， the use of immunosuppressive agents， and follow-up monitoring strategies can be a valuable reference.

Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

Objective:To investigated the clinical, biochemical, and immunohistological characteristics of patients with aldosterone producing adenoma(APA)and different gene mutations.Methods:The clinical and biochemical data of 206 patients with APA who received unilateral adrenalectomy were collected. Sanger sequencing was used to identify the mutation in the hot-point of KCNJ5 and other genes. The tumor samples were stained by 11β-hydroxylase(CYP11B1)and aldosterone synthase(CYP11B2), which was quantified by McCarty′s H-score system.Results:The gene mutations were identified in 166 out of 206(80.6%)patients with APA, of which 158 cases were KCNJ5 mutation, 2 ATP1A1 mutation, 5 ATP2B3 mutation, and 1 CTNNB1 mutation. Age, duration of hypertension, and serum potassium in APA patients with genetic mutant were significantly lower than those without genetic mutation( P<0.05) while the proportion of female, systolic blood pressure, diastolic blood pressure, aldosterone/renin ratio(ARR), and plasma aldosterone concentration(PAC)post saline infusion test(SIT)were significantly higher( P<0.05). Subgroup analysis showed that age, duration of hypertension, systolic blood pressure, and proportion of left ventricular hypertrophy in APA patients with ATP1A1 and ATP2B3 mutations were significantly higher than those with KCNJ5 mutation( P<0.05)while the PAC post SIT and tumor diameter were significantly lower( P<0.05). The positive rates of CYP11B2 in APA with different mutations were not significantly different. The H-score of CYP11B1 was significantly higher [160.0(127.5, 193.5) vs 80.0(27.5, 152.3), P=0.020] and the H-score of CYP11B2 was significantly lower [155.0(123.0, 190.0) vs 240.0(140.0, 270.0), P<0.01] in APA with KCNJ5 mutation compared with those with ATPase mutation. Conclusion:The types of genetic mutation are closely correlated with the clinical, biochemical, and immunohistological phenotypes in patients with APA.

Objective:To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome.Methods:The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc.Results:Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4.Conclusions:The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.

Objective: To evaluate the value of CYP11B2 immunohistochemistry in the histopathological diagnosis of primary aldosteronism(PA) among Chinese population. Methods: Ninety-six cases of unilateral PA patients were retrospectively enrolled, and with 15 cases of non-hyperfunctioning adenoma, and 15 cases of cortisol producing adenoma as control. CYP11B2 immunohistochemistry was performed in the tumor sections of these patients and was analysed by semi-quantified method. The positive rate of CYP11B2 in tumor specimen of all cases enrolled was calculated and PA patients were subtypely classified based on their histopathological features and CYP11B2 expressions. Results: The immune-positive rate of CYP11B2 in the PA group was 91.7% (88/96), with the control group being 6.7% (2/30, P<0.001). Subgroup analysis revealed that the immune-positive rate of CYP11B2 in the aldosterone producing adenoma group and unilateral hyperplasia group were 91.8% (78/85) and 90.9% (10/11), respectively. Based upon histopathological feature and CYP11B2 immunohistochemistry, PA patients were further subtypely classified as aldosterone producing adenoma (85/96), unilateral diffuse adrenocortical hyperplasia (7/96), unilateral mono-adrenocortical micronodules (1/96), unilateral multiple adrenocortical micronodules (1/96), and unilateral multiple aldosterone-producing cell clusters (multiple APCCs, 2/96). Conclusion CYP11B2 immunohistochemistry may serve as an useful tool for the histopathological diagnosis of PA.

A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2:MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.

Primary aldosteronism is a common cause of endocrine hypertension. Aldosterone-producing adenoma and bilateral idiopathic hyperplasia are the two major subtypes of primary aldosteronism. Unilateral adrenal hyperplasia as one of the rare subtypes was seldom reported. Herein, we present in detail a patient with unilateral adrenal hyperplasia difficult to be subtyped. By discussing several key points of the diagnosis and treatment process, some useful experiences and information are provided for the clinicians.