Objective:To observe the effect of metformin on intestinal metabolites and its protective effect on lung injury in an elderly sepsis rat.Methods:SD rats were fed at the Animal Laboratory Center of Zhengzhou University, fourteen elderly SD rats were randomly divided into three groups: sham surgery (age-Sham, AgS group, n=4), cecal ligation and perforation induced sepsis (age-Cecal ligation and puncture, AgCLP group, n=5), and oral administration of metformin (100 mg/kg) after 1 h of CLP treatment (age-Metformin, AgMET group, n=5). Collected rat feces 24 h after modeling, and analyzed the composition and inter group differences of metabolites in the feces using liquid chromatography tandem mass spectrometry non targeted metabolomics. Collected rat lung tissues and detected the expression levels of inflammation related genes and pathological changes in the tissue. The visualization of metabolic changes between groups were presented using orthogonal partial least squares discriminant analysis, heatmaps, and unsupervised principal component analysis, respectively. MetaboAnalyst 3.0 was used to evaluate the Pathway analysis of metabolites, and this software was based on the KEGG database and the human metabolome database. Results:The expressions of CCL4 ( F=203.00, P<0.001), CXCL1( F=65.69, P<0.001), IL-6 ( F=38.94, P<0.002), TNF-α ( F=14.85, P=0.005) between two groups of rats were significantly different (all P<0.05). However, there was no significant difference in CCL2 expression between AgCLP group and AgMET group. Furthermore, compared with the AgS group, the relative intensities of 17 metabolites such as 7-methylxanthine, N-Arachidonylglycine and Manolide in AgCLP group were significantly increased, whereas the 9 metabolites such as Phenazone, Gly-Phe and Valyproline were significantly decreased, and metformin treatment could reverse these changes of the above metabolites. Correlation analysis showed that the IL-6 and TNF-α levels were positively correlated with the relative strength of 7-Methylxanthine, N-Arachidonylglycine and other metabolites, but negatively correlated with the Phenazone and Gly-Phe. CCL4 and CXCL1 were positively correlated with Manolide, but negatively correlated with Valyproline. Conclusion:The results of this study showed that metformin improved sepsis induced acute lung injury and regulates the host intestinal metabolites, which might provide a potential and effective treatment for elderly sepsis induced acute lung injury.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Objective:To explore an applicative value of a 5-type precise diagnostic technique in integrated precise repair and reconstruction of digit-tip injuries.Methods:From March 2012 to June 2022, 45 digit-tip injuries (38 patients, with an average age of 33 years old) were classified under microscope on the basis of effectiveness of blood vessels remained in the severed tissue. Among the injured digits, there were 15 thumbs, 9 index fingers, 16 middle fingers, 4 ring fingers and 1 little finger. The diagnosis was categorised into 5 types according to involvement of blood vessels: Type I, injury of proper palmar digital artery (10 digits) ; Type II, injury of small artery (5 digits) ; Type Ⅲ, injury of whole vein (4 digits) ; Type IV, injury of superficial palmar arch (4 digits) ; and Type V, vessels missing (22 digits). The timing and therapeutic method of surgery were selected based on the precise classification of 5 types of diagnosis: (1) For type Ⅰ-Ⅳ injuries, 16 patients (23 digits) received in situ tissue replantation after emergency classification. Of which, type Ⅰ-Ⅱ injuries received conventional replantation, type Ⅲ injuries had replantation with arterialised vein, and type IV injuries received replantation with artery-vein shunt. (2) For the type V injuries, 22 patients (22 digits), staged and categorised flap reconstruction with toe flaps were performed. Of which, 7 were performed in emergency surgery, 12 in subemergency surgery and 3 in elective surgery. Based on the severity of defects, small tissue flaps of toe were used in reconstruction of type V injuries and following toe flaps were employed: 9 hallux nail flaps, 3 hallux nail flaps (for reconstruction of distal phalanx), 5 hallux fibular flaps, 3 hallux abdominal flaps and 2 compound tissue flaps with nail bed of the second toe. The sizes of the 45 replanted/transferred tissues flaps were 1.0 cm×0.6 cm×0.4 cm-2.2 cm×1.5 cm×0.8 cm. Donor sites directly sutured. Medical APP was applied in the rehabilitation exercises. Functions of digits were assessed by scheduled follow-ups at outpatient clinic and via remote medical APP to evaluate the clinical efficacy.Results:All small tissue blocks and (or) tissue flaps survived after replantation and (or) flap reconstruction of 45 injured digits. Postoperative follow-up lasted for 6 months to 7 years, with 36 months in average. The appearances of the reconstructed digit-tips were close to normal digits, with TPD at 3-7 mm. According to the Michigan Hand Outcomes Questionnaire (MHQ), 32 patients (37 digits) were in excellent, 5 patients (7 digits) in good, and 1 patient (1 digit) in poor, with 97.78% of excellent and good rate.Conclusion:Five-type precise diagnostic technique is the key to the integrated and precise reconstruction of digit-tip injuries. This method has been clinically validated and achieved realistic recovery from the injured digits.

Infectious diseases of spine (IDS) refer to a series of infectious diseases in different parts of the spine (vertebral body, intervertebral disc, appendix of vertebra, spinal canal, and adjacent paravertebral tissues) caused by various pathogenic microorganisms, accounting for about 2%~7% of systemic musculoskeletal system infections. According to the classic classification IDS can be divided into two types: specific infection and non-specific infection. IDS often has an insidious onset, atypical clinical manifestations, and less-specific imaging and laboratory tests, which causes great difficulties for the accurate diagnosis and treatment, often leading to missed diagnosis, misdiagnosis, and even mistreatment. Problems such as disordered clinical diagnosis and treatment procedures, diverse treatment methods, and non-standard medication and course of treatment still affect the prognosis of IDS. This article reviews the current research progress of the diagnosis and treatment process of IDS, in order to further standardize the diagnosis and treatment process of IDS.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Primary liver cancer is the fourth most common malignancy and the second most common cause of cancer death in China, posing a serious threat to the health of Chinese people. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers, among them 66% of patients are with intermediate-advanced HCC. Therefore, prevention strategies and conversion therapies to patients with intermediate-advanced HCC are particularly important. Hepatic arterial infusion chemotherapy (HAIC) is one of the important treatment methods to treat intermediate-advanced HCC. The tumor objective response rates and surgery conversion rates of HAIC-based conversion therapies are promising. The authors review the history of HAIC and the HAIC-based conversion therapies in this article.

Prostate cancer is one of the leading cause of male cancer-related death worldwide, and the treatment of high-risk prostate cancer and castration resistant prostate cancer remains a significant challenge. Epigenetic modification has been paid more attention in the field of tumor, as a common RNA modification in eukaryotic cells, N6-methyladenosine (m6A) methylation is a dynamic and reversible process regulated by m6A methyltransferase, demethylase and recognition protein, which can regulate the physiological process and tumor progression by regulating gene expression. m6A modification plays an important role in the occurrence and development of prostate cancer and is expected to become a new target in diagnosis, treatment and prognosis. This article reviews the m6A modification and its expression, function and mechanism in prostate cancer, as well as new ideas for clinical application.

Recent years, the incidence of prostate cancer is increasing, and the need of novel and effective diagnosis and treatment for prostate cancer is becoming more and more urgent.Monoamine oxidase A (MAO-A) is a mitochondrial binding enzyme, which plays an important role in the deamination of some neurotransmitters. Currentlly, some novel studies have shown that MAO-A plays an important role in the occurrence, development and metastasis of prostate cancer. At present, MAO-A has become a potential therapeutic target of prostate cancer and has been widely concerned. This article make a review on the possible mechanism of MAO-A in the occurrence, development and metastasis of prostate cancer and the application of MAO-A in the diagnosis and treatment of prostate cancer.

Objective:To evaluate the three-dimensional soft tissue changes at nasolabial region of female patients with maxillary protrusion after orthognathic surgery with maxillary setback.Methods:Peking University School and Hospital of Stomatology admitted 88 female patients with maxillary protrusion, aged 18-42 years old, with an average age of 28.2 years old. The segmental Le Fort Ⅰ osteotomies were performed in all patients with extraction of maxillary first premolars to create space for maxillary setback. The patients with maxillary protrusion and mandibular retraction received bilateral sagittal split ramus osteotomy(BSSRO)to move mandibular body, while the patients with bimaxillary protrusion received subapical osteotomy. 3dMD photos were taken preoperative 1-3 days and at least 6 months after operation to obtain three-dimensional facial images. The postoperative soft tissue changes of three-dimensional landmarks, line space and angles were measured with the use of Geomagic Studio 2013, and three-dimensional deviation analysis was applied. Paired t test was performed on the measured results. P<0.05 was considered statistically significant. Results:The distance of the subnasale in sagittal direction in patients with maxillary protrusion was (-10.90±18.60) mm preoperatively, (-10.05±18.62) mm ( t=-7.66, P<0.001)postoperatively, and setback of (0.85±1.00) mm; Labrale superius was (-15.18±18.67) mm preoperatively, (-11.92±18.9) mm postoperatively, and setback of (3.26±1.40) mm. Preoperative nasal width was (37.32±2.32) mm, postoperative for (38.08±2.32) mm ( t=-4.85, P<0.001)and increased by (0.76±1.47) mm.The lip width was (49.17±3.54) mm before surgery and (47.68±3.74) mm ( t=5.77, P<0.001)after surgery ( t=5.77, P<0.001), decreased by (1.49±2.42) mm. Philtrum length was (15.20±2.32) mm preoperatively and (15.78±2.17) mm ( t=-4.70, P<0.001)postoperatively, increased by (0.58±1.16) mm; The nasolabial angle was 101.98°±9.34° before surgery and 109.05°±8.59° ( t=-12.36, P<0.001)after surgery, increased by 6.99°±5.35°. The three-dimensional deviation analysis result showed that the soft tissue in the parasnasal area was moved forward (1.54±0.73) mm. Conclusions:3dMD can reflect the three-dimensional soft tissues changes after orthognathic surgery directly and accurately. After maxillary setback, the nasal base and upper lip of patients were significantly retrograded, and the paranasal area appeared forward, accompanied by increase in the nasolabial angle, lengthening of the philtrum length, vermillion length decrease, increase in nasal width and decrease in lip width.

Objective:To evaluate the three-dimensional soft tissue changes at nasolabial region of female patients with maxillary protrusion after orthognathic surgery with maxillary setback.Methods:Peking University School and Hospital of Stomatology admitted 88 female patients with maxillary protrusion, aged 18-42 years old, with an average age of 28.2 years old. The segmental Le Fort Ⅰ osteotomies were performed in all patients with extraction of maxillary first premolars to create space for maxillary setback. The patients with maxillary protrusion and mandibular retraction received bilateral sagittal split ramus osteotomy(BSSRO)to move mandibular body, while the patients with bimaxillary protrusion received subapical osteotomy. 3dMD photos were taken preoperative 1-3 days and at least 6 months after operation to obtain three-dimensional facial images. The postoperative soft tissue changes of three-dimensional landmarks, line space and angles were measured with the use of Geomagic Studio 2013, and three-dimensional deviation analysis was applied. Paired t test was performed on the measured results. P<0.05 was considered statistically significant. Results:The distance of the subnasale in sagittal direction in patients with maxillary protrusion was (-10.90±18.60) mm preoperatively, (-10.05±18.62) mm ( t=-7.66, P<0.001)postoperatively, and setback of (0.85±1.00) mm; Labrale superius was (-15.18±18.67) mm preoperatively, (-11.92±18.9) mm postoperatively, and setback of (3.26±1.40) mm. Preoperative nasal width was (37.32±2.32) mm, postoperative for (38.08±2.32) mm ( t=-4.85, P<0.001)and increased by (0.76±1.47) mm.The lip width was (49.17±3.54) mm before surgery and (47.68±3.74) mm ( t=5.77, P<0.001)after surgery ( t=5.77, P<0.001), decreased by (1.49±2.42) mm. Philtrum length was (15.20±2.32) mm preoperatively and (15.78±2.17) mm ( t=-4.70, P<0.001)postoperatively, increased by (0.58±1.16) mm; The nasolabial angle was 101.98°±9.34° before surgery and 109.05°±8.59° ( t=-12.36, P<0.001)after surgery, increased by 6.99°±5.35°. The three-dimensional deviation analysis result showed that the soft tissue in the parasnasal area was moved forward (1.54±0.73) mm. Conclusions:3dMD can reflect the three-dimensional soft tissues changes after orthognathic surgery directly and accurately. After maxillary setback, the nasal base and upper lip of patients were significantly retrograded, and the paranasal area appeared forward, accompanied by increase in the nasolabial angle, lengthening of the philtrum length, vermillion length decrease, increase in nasal width and decrease in lip width.