Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs). METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines. RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1ß [standardized mean difference (SMD) = -1.94, 95% confidence interval (CI) (-2.99, -0.90), P = 0.0003], IL-6 [SMD = -1.65, 95% CI (-2.33, -0.97,) P < 0.000 01], IL-17 [SMD = -2.41, 95% CI (-3.61, -1.20), P < 0.0001], tumor necrosis factor (TNF)-α [SMD = -1.84, 95% CI (-2.61, -1.06), P < 0.0001], and interferon (IFN)-γ [SMD = -1.54, 95% CI (-2.43, -0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI (0.15, 2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI (1.39, 2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD = -0.63, 95% CI (-1.82, 0.57), P = 0.30]. CONCLUTIONS: Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis.

OBJECTIVE: In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. METHODS: Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. RESULTS: Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69 ± 8.32 years vs. 63.05 ± 8.44 years, P < 0.001), larger tumour size ≥4 cm (P = 0.006), advanced T stage (P = 0.024), N stage (P = 0.041), Tumor, Node and Metastasis (TNM) stage (P = 0.029) and postoperative complications (P = 0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P = 0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P = 0.032). CONCLUSION: In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice.

Psoriasis is an autoimmune disease, which has a significant impact on the quality of patient's life. And, there is still no cure for psoriasis. The human dental pulp stem cell (hDPSC) possesses the properties of immunoregulation. In this study, we aimed to determine the effect of hDPSC on the imiquimod (IMQ)-induced psoriasis in mice. The psoriasis model was established by topical application of IMQ cream in mice for 7 days. We found that subcutaneous injection of hDPSC could reduce the symptoms of skin lesions in IMQ-induced psoriasis and suppress the expression of keratin 16, S100A8, S100A9, which are associated with abnormal epidermal proliferation. Subepithelial inflammatory cytokines, CD4+ T lymphocytes and CD11c+ dendritic cells infiltrations were significantly inhibited in by hDPSC. The TNF-α, IFN-γ expressions in serum were decreased, and splenomegaly induced by IMQ was improved after hDPSC treatment. In summary, our study demonstrated that hDPSC could reduce the symptoms of skin lesions and suppress local and systemic immune responses of IMQ-induced psoriasis in mice, which might provide a new sight for the treatment of psoriasis.

Clinical Effect of Shugan Hewei Prescription Combined with Vonoprazan on Refractory Gastroesophageal Reflux Disease Due to Qi Depression and Phlegm Obstruction / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease （RGERD） due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group （Shugan Hewei prescription， one bag each time， twice a day + vonoprazan， 20 mg each time， once a day） and a control group （vonoprazan， 20 mg each time， once a day） by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms （pharyngeal discomforts such as phlegm obstruction， retrosternal discomfort， and belching）， somatic symptoms， quality of life， and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study， including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%（34/38）， which was higher than that （62.16%，23/37） in the control group （χ2=13.014， P<0.01）. After treatment， the scores of esophageal mucous membrane， reflux disease symptoms， TCM symptoms， gastroesophageal reflux disease health-related quality of life scale （GERD-HRQL）， and somatic self-rating scale （SSS） decreased in both groups（P<0.05）. Moreover， the observation group outperformed the control group in alleviating heartburn， acid reflux， throat discomforts， midnight coughing， nausea and dry vomiting， mucousy mouth， and insomnia in the patients with GERD （P<0.05，P<0.01）. However， the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms， physical signs， quality of life， and somatic symptoms， without causing obvious adverse effects.

Effect of peroxisome proliferator-activated receptor γ on skin physiological and pathological processes / 中华皮肤科杂志

Peroxisome proliferator-activated receptors (PPARs) are widely involved in lipid metabolism, glucose metabolism, cell growth and differentiation, and inflammation in the human body. PPARγ agonists can inhibit skin inflammatory response, protect epidermal barrier function, and repair skin injury. This review summarizes various roles of PPARγ in skin biology, and discusses its function in skin diseases, such as psoriasis and skin tumors.

Lipocalin 2 in the Paraventricular Thalamic Nucleus Contributes to DSS-Induced Depressive-Like Behaviors / 神经科学通报·英文版

The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases (IBD) than in the general population. The mechanisms underlying dextran sulfate sodium (DSS)-induced depressive-like behaviors are still unclear. We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors. The paraventricular thalamic nucleus (PVT) was regarded as the activated brain region by the number of c-fos-labeled neurons. RNA-sequencing analysis showed that lipocalin 2 (Lcn2) was upregulated in the PVT of mice with DSS-induced depressive behaviors. Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability. Moreover, Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors. The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.

Efficacy of human umbilical cord mesenchymal stem cells via different transplantation approaches in treatment of rats with liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of the frozen and fresh preparations of human umbilical cord mesenchymal stem cells （hUC-MSC） on a rat model of liver cirrhosis after transplantation via the portal vein or the caudal vein. MethodsA total of 70 specific pathogen-free healthy male Sprague-Dawley rats were randomly divided into normal group （13 rats fed with ordinary tap water and rat food） and liver cirrhosis model group （57 rats given subcutaneous multi-point injection of mixed carbon tetrachloride/olive oil solution）. At week 8， the growth of rats was observed for both groups， and 3 rats were selected from each group for histopathological examination to confirm the formation of liver cirrhosis. A total of 50 rats were selected from the liver cirrhosis model and were divided into model group， portal vein group+fresh cell preparation group， portal vein+frozen cell preparation group， caudal vein+fresh cell preparation group， and caudal vein+frozen cell preparation group using a random number table， with 10 rats in each group. Fresh or frozen hUC-MSC were transplanted via the portal vein or the caudal vein， and after 4 weeks of administration， the different groups were compared in terms of the changes in liver function parameters and liver fibrosis degree. Continuous data were expressed as mean±standard deviation， and the independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAt week 8 of modeling， the model group showed the formation of pseudolobules of different sizes in the liver and met the diagnostic criteria for liver cirrhosis， with significant increases in the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， and alkaline phosphatase （ALP） compared with the normal group （all P<0.001）， suggesting that the rat model of liver cirrhosis was established successfully. There were significant differences in the levels of ALT， AST， TBil， and ALP between the five groups （F=232.00， 177.10， 112.30， 121.70， all P<0.001）. Further comparison between two groups showed that the model group had significantly higher levels of ALT， AST， TBil， and ALP than the normal group （all P<0.01）， and the portal vein group+fresh cell preparation group， the portal vein+frozen cell preparation group， the caudal vein+fresh cell preparation group， and the caudal vein+frozen cell preparation group had significantly lower levels of ALT， AST， TBil， and ALP than the model group （all P<0.01）. ConclusionThere are significant improvements in liver function and liver fibrosis degree in a rat model of liver cirrhosis at week 4 after the transplantation of hUC-MSC， and frozen or fresh cell preparation and different transplantation approaches have no significant influence on treatment outcome.

An MRI study of lateral vascular safety zones in oblique lumbar interbody fusion surgery / 中国修复重建外科杂志

OBJECTIVE@#To study the anatomical characteristics of blood vessels in the lateral segment of the vertebral body through the surgical approach of oblique lumbar interbody fusion (OLIF) using MRI imaging, and evaluate its potential vascular safety zone.@*METHODS@#The lumbar MRI data of 107 patients with low back and leg pain who met the selection criteria between October 2019 and November 2022 were retrospectively analyzed. The vascular emanation angles, vascular travel angles, and the length of vessels in the lateral segments of the left vertebral body of L 1-L 5, as well as the distance between the segmental vessels in different Moro junctions of the vertebral body and their distances from the edges of the vertebrae in the same sequence (bottom marked as I, top as S) were measured. The gap between the large abdominal vessels and the lateral vessels of the vertebral body was set as the lateral vascular safe zones of the lumbar spine, and the extent of the safe zones (namely the area between the vessels) was measured. The anterior 1/3 of the lumbar intervertebral disc was taken as the simulated puncture center, and the area with a diameter of 22 mm around it as the simulated channel area. The proportion of vessels in the channel was further counted. In addition, the proportions of segmental vessels at L 5 without a clear travel and with an emanation angel less than 90° were calculated.@*RESULTS@#Except for the differences in the vascular emanation angles between L 4 and L 5, the vascular travel angles between L 1, L 2 and L 4, L 5, and the length of vessels in the lateral segments of the vertebral body among L 1-L 4 were not significant ( P>0.05), the differences in the vascular emanation angles, vascular travel angles, and the length of vessels between the rest segments were all significant ( P<0.05). There was no significant difference in the distance between vessels of L 1, L 2 and L 2, L 3 at Moro Ⅰ-Ⅳ junctions ( P>0.05), in L 3, L 4 and L 4, L 5 at Ⅱ and Ⅲ junction ( P>0.05). There was no significant difference in the vascular distance of L 2, L 3 between Ⅱ, Ⅲ junction and Ⅲ, Ⅳ junction, and the vascular distance of L 3, L 4 between Ⅰ, Ⅱ junction and Ⅲ, Ⅳ junction ( P>0.05). The vascular distance of the other adjacent vertebral bodies was significant different between different Moro junctions ( P<0.05). Except that there was no significant difference in the distance between L 2I and L 3S at Ⅰ, Ⅱ junction, L 3I and L 4S at Ⅱ, Ⅲ junction, and L 2I and L 3S at Ⅲ, Ⅳ junction ( P>0.05), there was significant difference of the vascular distance between the bottom of one segment and the top of the next in the other segments ( P<0.05). Comparison between junctions: Except for the L 3S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ junction, and L 5S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ and Ⅲ, Ⅳ junctions had no significant difference ( P>0.05), there were significant differences in the distance between the other segmental vessels and the vertebral edge of the same sequence in different Moro junctions ( P<0.05). The overall proportion of vessels in the simulated channels was 40.19% (43/107), and the proportion of vessels in L 1 (41.12%, 44/107) and L 5 (18.69%, 20/107) was higher than that in the other segments. The proportion of vessels in the channel of Moro zone Ⅰ (46.73%, 50/107) and zone Ⅱ (32.71%, 35/107) was higher than that in the zone Ⅲ, while no segmental vessels in L 1 and L 2 were found in the channel of zone Ⅲ ( χ 2=74.950, P<0.001). Moreover, 26.17% (28/107) of the segmental vessels of lateral L 5 showed no movement, and 27.10% (29/107) vascular emanation angles of lateral L 5 were less than 90°.@*CONCLUSION@#L 1 and L 5 segmental vessels are most likely to be injured in Moro zones Ⅰ and Ⅱ, and the placement of OLIF channels in L 4, 5 at Ⅲ, Ⅳ junction should be avoided. It is usually safe to place fixation pins at the vertebral body edge on the cephalic side of the intervertebral space, but it is safer to place them on the caudal side in L 1, 2 (Ⅰ, Ⅱ junction), L 3, 4 (Ⅲ, Ⅳ junction), and L 4, 5 (Ⅱ, Ⅲ, Ⅳ junctions).

Distribution and drug resistance of pathogenic bacteria for infection after liver transplantation / 临床肝胆病杂志

Objective To investigate the distribution and drug resistance of pathogenic bacteria for infection after liver transplantation, and to provide a scientific basis for the rational clinical application of antibiotics. Methods The pathogenic bacteria isolated from the specimens of 904 patients with infection after liver transplantation in The Affiliated Hospital of Qingdao University from March 2014 to December 2021 were analyzed in terms of distribution and drug resistance. WHONET 5.6 software was used to perform a statistical analysis of strains and bacterial resistance rate, and Excel was used to analyze the sources of specimens, composition ratios, and distribution of pathogenic bacteria. Results A total of 2 208 non-repetitive pathogenic bacteria were isolated, mainly from the specimens of respiratory tract (31.25%), bile (22.28%), ascites (13.18%), blood (8.38%), and drainage fluid (4.62%). The top 10 pathogenic bacteria were Klebsiella pneumoniae subspecies (10.69%), Enterococcus faecium (10.42%), Escherichia coli (8.24%), Pseudomonas aeruginosa (8.24%), Staphylococcus epidermidis (8.06%), Acinetobacter baumannii (7.93%), Stenotrophomonas maltophilia (6.61%), Enterobacter cloacae (3.22%), Staphylococcus haemolyticus (3.08%), and Staphylococcus aureus (2.94%), accounting for 69.43% of the total pathogenic bacteria. Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Klebsiella pneumoniae subspecies, and Acinetobacter baumannii were the main pathogenic bacteria isolated from respiratory tract specimens; Enterococcus faecium was the main pathogenic bacterium isolated from bile, ascites, and drainage fluid specimens; Escherichia coli , Staphylococcus epidermidis , and Klebsiella pneumoniae subspecies were the main pathogenic bacteria isolated from blood specimens. Drug sensitivity data showed that Enterobacterales bacteria had a relatively high resistance rate to cephalosporins and fluoroquinolones and a resistance rate of 50% to macrolides, fluoroquinolones, sulfonamides, and lincomycin, and a small part of these strains were resistant to linezolid and quinupristin/dalfopristin (< 3%), with no Staphylococcus epidermidis strains resistant to tigecycline and vancomycin. A total of 287 drug-resistant strains were monitored, accounting for 13%, among which there were 128 carbapenem-resistant Acinetobacter baumannii strains, 88 carbapenem-resistant Pseudomonas aeruginosa strains, 26 carbapenem-resistant Klebsiella pneumoniae subspecies strains, 11 carbapenem-resistant Escherichia coli strains, 23 methicillin-resistant Staphylococcus aureus strains, and 11 vancomycin-resistant Enterococcus strains. The carbapenem-resistant Klebsiella pneumoniae subspecies strains mainly produced serine carbapenemase, and the carbapenem-resistant Escherichia coli strains mainly produced metal β-lactamase. Conclusion Gram-negative bacteria are the main pathogenic bacteria for infection after liver transplantation, and there are differences in the distribution of pathogenic bacteria between different types of specimens. The resistance rate of some strains tend to increase, and therefore, it is necessary to strengthen the management of nosocomial infection and antibiotics.

Anti-inflammatory Mechanism of Modified Erchentang on Chronic Obstructive Pulmonary Disease Through Jagged1/Notch1/Hes1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease （COPD） and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose modified Erchentang groups （5， 10， 20 g·kg-1）， and γ-secretase inhibitor DAPT group （0.02 g·kg-1）， with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide （LPS）. Rats were treated with corresponding drugs by gavage， while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1， soluble intercellular adhesion molecule-1 （sICAM-1）， activated leukocyte cell adhesion molecule （ALCAM）， and soluble vascular adhesion molecule-1 （sVCAM-1） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of Jagged1， Notch1， and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of Jagged1， Notch1， Notch1 intracellular domain （NICD1）， and Hes1 in lung tissues of rats was detected by immunohistochemistry （IHC）. ResultCompared with the normal group， the model group showed increased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.01）， increased mRNA expression of Jagged1， Notch1， and Hes1 in lung tissues （P<0.01）， and increased protein expression of Jagged1， Notch1， NICD1， and Hes1 （P<0.01）. Compared with the model group， the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.05， P<0.05）， down-regulated mRNA expression of Jagged1， Notch1， and Hes1 （P<0.05， P<0.01）， and reduced protein expression of Jagged1， Notch1， NICD1， and Hes1（P<0.05， P<0.01）. ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats， and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1， Notch1， and Hes1 and inhibiting the release of Notch1， sICAM-1， ALCAM， and sVCAM-1.

Generalized pulp canal obliteration in a patient on long-term glucocorticoids: a case report and literature review.

BACKGROUND: The calcification of the tooth pulp is a pathological condition that occurs in response to various factors. A uncommon haematological condition known as paroxysmal nocturnal haemoglobinuria (PNH) is characterized by bouts of haemolysis, and it requires long-term use of glucocorticoids (GCs). CASE PRESENTATION: A female patient who was diagnosed with PNH and had a history of long-term use of GCs came to our department for root canal therapy (RCT) for teeth 25, 26, and 27. The radiographs showed generalized pulp canal obliteration (PCO) in most of the patients. None of these teeth (25, 26, or 27) were sensitive to percussion, and they did not respond to thermal or electrical sensitivity tests. A diagnose of pulp necrosis was made for these teeth. RCT was carried out with the help of an oral microscope, and then a prosthodontic procedure was created for the teeth. CONCLUSIONS: Based on the patient's long history use of GCs and a series of related studies, we conclude that the long-term usage of GCs contributes significantly to the onset of PCO.

The Role of TAK1 in RANKL-Induced Osteoclastogenesis.

Bone remodelling is generally a dynamic process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts are the only cell type capable of bone resorption to maintain bone homeostasis in the human body. However, excessive osteoclastogenesis can lead to osteolytic diseases. The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) has been widely considered to be an important modulator of osteoclastogenesis thereby participating in the pathogenesis of osteolytic diseases. Transforming growth factor ß-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is an important intracellular molecule that regulates multiple signalling pathways, such as NF-κB and mitogen-activated protein kinase to mediate multiple physiological processes, including cell survival, inflammation, and tumourigenesis. Furthermore, increasing evidence has demonstrated that TAK1 is intimately involved in RANKL-induced osteoclastogenesis. Moreover, several detailed mechanisms by which TAK1 regulates RANKL-induced osteoclastogenesis have been clarified, and some potential approaches targeting TAK1 for the treatment of osteolytic diseases have emerged. In this review, we discuss how TAK1 functions in RANKL-mediated signalling pathways and highlight the significant role of TAK1 in RANKL-induced osteoclastogenesis. In addition, we discuss the potential clinical implications of TAK1 inhibitors for the treatment of osteolytic diseases.

Clinical efficacy of hepatic artery chemoembolization combined with systemic treatment in the treatment of recurrent hepatocellular carcinoma with abdominal lymph node metastasis / 中华消化外科杂志

In China, patients with hepatocellular carcinoma (HCC) are usually with late stage and long medical history when diagnosed, resulting in a lower 5-year survival rate. For advanced HCC, guidelines from different countries have different indications for local treatment. The applica-tion of hepatic artery chemoembolization has brought new treatment opportunities to patients with advanced HCC. Due to tumor heterogeneity, the response to immunotherapy is different in patients with intrahepatic recurrent lesions and extrahepatic metastatic lesions of primary hepatic carcinoma. Therefore, hepatic artery chemoembolization combined with systemic treatment is beneficial to prolong the survival of patients. The authors introduce the clinical experience of a patient with recurrent advanced HCC combined with abdominal lymph node metastasis who was treated with hepatic artery chemoembolization combined with atezolizumab plus bevacizumab. The results show that tumor is controlled in a short period with a good clinical effect.

Clinical analysis of breast reconstruction with single-port inflatable endoscopic prepectoral prosthesis implantation / 国际外科学杂志

Objective:To investigate the surgical method and clinical application value of single-port inflatable endoscopic prepectoralis prosthesis implantation for breast reconstruction (external prosthesis wrapping Off-Label).Methods:From September 2021 to February 2022, 7 breast cancer patients who underwent single-port inflatable endoscopic prepectoralis prosthesis implantation breast reconstruction (Off-Label) in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. Statistical analysis of surgical complications, postoperative movement deformities, postoperative chest wall pain, postoperative quality of life and satisfaction scores of patients were conducted.Results:All 7 patients successfully completed the operation. There were no complications such as postoperative bleeding, infection, ischemic necrosis of nipple-areola complex or skin flap, postoperative movement deformity, postoperative chest wall pain, capsular contracture, prosthesis exposure or removal. The BREAST-Q scale was used to evaluate the quality of life and satisfaction after breast reconstruction. Postoperative breast satisfaction (55-100 points), chest wall status (52-89 points), and social psychological status (62-100 points) can be compared High rating.Conclusion:The single-port inflatable endoscopic prepectoral prosthesis implantation breast reconstruction (Off-Label) can achieve better radical effect and cosmetic effect through a shorter operation time, and the postoperative quality of life and satisfaction of patients are higher.

Comparison of efficacy of femoral tunnel creation with figure-of-four position and traditional knee hyperflexed position for arthroscopic anterior cruciate ligament reconstruction using tendon autograft / 中华创伤杂志

Objective:To compare the efficacy of arthroscopic anterior cruciate ligament reconstruction using tendon autograft with figure-of-four position and traditional knee hyperflexed position for femoral tunnel creation.Methods:A retrospective case series study was conducted to analyze the clinical data of 46 patients with ACL injury admitted to Second Affiliated Hospital of Harbin Medical University from August 2019 to October 2019, including 26 males and 20 females; aged 24-40 years [(31.1±7.5)years]. All patients underwent arthroscopic ACL reconstruction using tendon autograft. The femoral tunnel was created with figure-of-four position in 21 patients (figure-of-four position group) and with traditional knee hyperflexed position in 25 patients (knee hyperflexed position group). The operation time was compared between the two groups. The center position, length and angle of femoral tunnel were evaluated and measured by three dimensional CT reconstruction and Bernard quadrant method at 8 weeks postoperatively. The knee function was assessed by knee Lysholm score preoperatively, at 8 weeks and at 1 year postoperatively. Complications were observed as well.Results:All patients were followed up for 2-20 months [(15.3±2.1)months]. The operation time was (28.5±2.6)minutes in figure-of-four position group, significantly less than (39.5±2.4)minutes in knee hyperflexed position group ( P<0.05). The tunnel center position was located at (27.1±1.4)% and (25.1±2.6)% within the Bernard quadrant in figure-of-four position group, similar with (28.1±2.8)% and (26.1±3.1)% in knee hyperflexed position group (all P>0.05). Total tunnel length and thick tunnel length were (42.1±2.4)mm and (34.1±2.4)mm in figure-of-four position group, significantly longer than (38.2±2.5)mm and (31.1±2.7)mm in knee hyperflexed position group (all P<0.05). The coronal plane angle of the tunnel was (41.1±2.4)° in figure-of-four position group, significantly smaller than (47.5±2.6)° in knee hyperflexed position group ( P<0.05). The sagittal plane angle of the tunnel was (42.1±1.4)° in figure-of-four position group, significantly greater than (37.1±1.8)° in knee hyperflexed position group ( P<0.05). Figure-of-four position group showed the knee Lysholm score of (53.4±5.2)points preoperatively, (97.1±1.4)points at 8 weeks postoperatively and (98.3±2.3)points at 1 year postoperatively. Knee hyperflexed position group showed the knee Lysholm score of (54.3±7.4)points preoperatively, (97.1±1.6)points at 8 weeks postoperatively and (98.1±1.3)points at 1 year postoperatively. The knee Lysholm score did not differ significantly between the two groups (all P>0.05), but the knee function was significantly improved in both groups when compared with that before the operation (all P<0.05). There were 1 patient with femoral tunnel fracture, one with injury to the medial condylar cartilage and one with injury to the posterior root of lateral meniscus in knee hyperflexed position group, while no above-mentioned complications occurred in figure-of-four position group ( P<0.05). Conclusion:Arthroscopic ACL reconstruction using tendon autograft with femoral tunnel creation through figure-of-four position and traditional knee hyperflexed position can both contribute knee functional recovery, but the figure-of-four position has the advantages of short operation time, accurate tunnel positioning, favorable length and angle of the tunnel and less complications.

Protective effects of valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement / 中国药房

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

Clinical characteristics and prognosis of RUNX1-RUNX1T1 fusion gene-positive with ASXL2 gene mutations in acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of patients with RUNX1-RUNX1T1 fusion gene-positive acute myeloid leukemia (AML) with ASXL2 gene mutation.Methods:The clinical data of 145 newly diagnosed RUNX1-RUNX1T1 fusion gene-positive AML patients treated at the Second Hospital Center of Shanxi Medical University from October 2010 to March 2021 were retrospectively analyzed. Sanger sequencing was used to detect the gene mutation. According to the presence or absence of ASXL2 gene mutation, the patients were divided into mutation group and non-mutation group. The clinical characteristics, gene mutations and prognosis were compared among the two groups.Results:Among 145 AML patients with positive RUNX1-RUNX1T1 fusion gene, we identified recurrent mutations of c-kit, ASXL2, N/KRAS, FLT3, ASXL1, TET2, NPM1 and DNMT3A genes, with mutation rates of 40.7% (59/145), 20.7% (30/145), 15.9% (23/145), 12.4% (18/145), 11.7% (17/145), 11.0% (16/145), 5.5% (8/145), and 2.1% (3/145), respectively. A total of 18 mutation sites were detected in 30 patients with ASXL2 gene mutations including 5 point mutations and 13 frameshift mutations, which mainly occured in the exons 12 and 13. Lactate dehydrogenase (LDH) at initial diagnosis of 30 AML patients with ASXL2 mutation was lower than that of those with ASXL2 non-mutation ( Z = 2.34, P = 0.020), while prothrombin time (PT) of AML patients with ASXL2 mutation was longer than that of those with ASXL2 non-mutation ( Z = 1.99, P = 0.047). A total of 21 (21/30, 70%) patients simultaneously had other gene mutations. The incidence of RAS mutations in patients with ASXL2 mutation was higher than that those with ASXL2 non-mutation, and the difference was statistically significant [30.0% (9/30) vs. 12.1% (14/115), χ2 = 4.41, P = 0.036]. There were no statistically significant differences in complete remission rate [86.7% (26/30) vs. 74.8% (86/115)] and recurrence rate [43.3% (13/30) vs.31.3% (36/115)] of patients with ASXL2 mutation and ASXL2 non-mutation ( χ2 = 0.39, P = 0.534; χ2 = 0.54, P = 0.432). The median overall survival (OS) time was 26 months (1-135 months) and 30 months (1-120 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; the median disease-free survival (DFS) time was 14 months (0-60 months) and 13 months (0-94 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; and the differences in OS and DFS were not statistically significant of both groups ( χ2 = 0.05, P = 0.822; χ2 = 0.34, P = 0.562). Compared with ASXL1 mutant patients, cases with ASXL2 mutation had higher OS and DFS rates, and the differences were statistically significant ( P = 0.003, P = 0.007). The differences in OS and DFS between patients with ASXL2 mutations and those with positive mutations of c-kit, RAS, FLT3, TET2, NPM1, DNMT3A were not statistically significant (all P > 0.05). Conclusions:RUNX1-RUNX1T1 positive AML patients with ASXL2 mutation tend to have low LDH and high PT, and often coexist with RAS mutations, and their prognosis is better than that in patients with ASXL1 positive mutation.

HBcAg-specific Th9 cells in patients with HBV infection / 中华微生物学和免疫学杂志

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

Systematic evaluation of the relationship between tumor-infiltrating lymphocytes and prognosis of triple negative breast cancer / 国际外科学杂志

Objective:To investigate the prognostic value of tumor infiltrating lymphocytes (TILs) and their phenotypes, CD4 + TILs, CD8 + TILs and FOXP3 + TILs, in short-term prognosis (PCR) and long-term prognosis (DFS, OS) of triple negative breast cancer (TNBC), and to provide theoretical support for the immunotherapy of TNBC. Methods:A systematic surch of PubMed, Medline, Embase, Web of Science, CBM, CNKI was conducted to identified eligible articles. All prospective trials and observational controlled trials published before August 2020 were retrieved.The two authors independently evaluated the quality of the included literature, extracted the data, and conducted systematic evaluation and analysis using RevMan5.3 software.Results:A total of 48 literatures were included.Every 10% increase in TILs and TILs expression in the high-expression group predicted a higher PCR, OR were 1.81 (95% CI: 1.44-2.28) and 1.09 (95% CI: 1.02-1.15). For longer survival, the HR for DFS and OS were 0.99 (95% CI: 0.98-0.99) and 0.90 (95% CI: 0.86-0.94), 0.87 (95% CI: 0.79-0.96) and 0.88 (95% CI: 0.83-0.92). Phenotypic CD4 + TILs, CD8 + TILs, and FOXP3 + TILs did not show statistically significant differences in PCR among patients, but in long-term prognosis, higher infiltration predicted longer survival, with HR for DFS of 0.54 (95% CI: 0.36-0.80), 0.46(95% CI: 0.33-0.64) and 0.45(95% CI: 0.31-0.68). HR of OS were 0.49 (95% CI: 0.32-0.76), 0.59 (95% CI: 0.54-0.66) and 0.44 (95% CI: 0.27-0.71). Conclusion:The infiltration degree of TILs and the increase of TILs expression by 10% can be used as a prognostic index of TNBC.High levels of phenotypic infiltration of CD4 + TILs, CD8 + TILs, and FOXP3 + TILs predicted better long-term survival, but there was no statistically significant difference in short-term survival.

Quantificational evaluation of the resolving power of qualitative biomarkers with different cardinal numbers based on a magnitude-standardized index.

Biomarkers are used for clinical diagnostic purposes, but existing indexes exhibit limitations in terms of the resolving power of biomarkers. This paper proposes a new index, the magnitude-standardized index (MSI), to describe the quantitative variations and resolving powers of different biomarkers. In MSI analysis models, variation scales for ratios and differences are considered simultaneously, and a higher MSI value implies a stronger risk or effect for a biological factor. We explain the rationale for the MSI via hybrid and geometric methods and verify its efficacy through simulation experiments. Our results indicate that the MSI is superior to the Youden index and odds ratio for describing resolving power. When two biomarkers with similar Youden index values, odds ratios, or MSI values but different positive test rates (or cardinal numbers) were combined, all three index values increased; however, only the MSI value remained relatively stable. For a very small cardinal number, such as that of a single nucleotide polymorphism, the MSI value is at most half of the maximum value (0.5), allowing comparisons between MSI values for biomarkers with different cardinal numbers. The MSI can thus provide a better quantifiable evaluation of the resolving power of biomarkers with different cardinal numbers.