ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

Objective: To investigate the distribution of HPA, HLA alleles and haplotypes among apheresis platelet donors in Changsha, China, and to establish an apheresis platelet donor database. Methods: High-resolution genotyping of HLA-A and -B was performed using PCR sequence based typing (SBT) and next generation sequencing (NGS). HPA genotyping was conducted using quantitative PCR (Q-PCR). The allele frequency, haplotype frequency and linkage disequilibrium parameters were calculated using the direct counting method, the maximum likelihood method and Arlequin software (V 3.1). Results: A total of 41 HLA-A alleles and 82 HLA-B alleles were detected, and 457 HLA-A-B haplotypes were found, of which 25 showed strong linkage disequilibrium (RLD>0.50). The HPA-3 and HPA-15 had the highest HPA polymorphism and antigen mismatch rate in apheresis platelet donor database in Changsha, and the dual antigen mismatch rate was 0.3704 and 0.3743, respectively. Conclusion: The polymorphism of apheresis platelet donor database in Changsha is complex and has strong regional characteristics. Establishing a high-resolution donor database will strongly support the provision of genetically matched platelets for clinical use, facilitating precise platelet transfusion therapy.

Objective:To observe the protective effect of Jinbuhuan Jianwei Jiedu Decoction on gastric mucosa of rats with chronic atrophic gastritis (CAG); To explore its mechanism through the farnesyl ester X receptor (FXR)/G protein bile acid coupled receptor 5 (TGR5) pathway.Methods:Wistar rats were randomly divided into normal control group, model group, folic acid group, low-, medium-, and high-dosage groups, with 10 rats in each group. Except for the normal control group, the other rats were used to establish a CAG model by alternate gavage of 2% sodium salicylate+20 mmol/L sodium deoxycholate+methylnitrosoguanidine (MNNG) for free consumption. The folic acid group was treated with 1.43 mg/kg by gavage, while the low-, medium-, and high-dosage groups were treated with 9.68, 19.35 and 38.7 g/kg of Jinbuhuan Jianwei Jiedu Decoction by gavage, once a day, for 12 weeks. The gastric mucosal blood flow and histopathological changes in each group of rats were observed. Rat gastric juice was collected, and gastric juice pH and pepsin activity were detected. ELISA method was used to detect the levels of serum tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and total bile acid (TBA). Western-blot and RT-PCR were used to detect the protein and mRNA levels of FXR, TGR5, CDX2 and SOX2 in gastric mucosal tissue.Results:Compared with the normal control group, the gastric mucosal blood flow and pepsin activity in the low-, medium-, and high-dosage groups increased significantly, and the pH value of gastric juice of medium-, and high-dosage groups decreased ( P<0.05). The levels of TNF-α, IL-6, TBA in serum of low-, medium-, and high-dosage groups decreased ( P<0.05); and FXR, TGR5, CDX2 in gastric mucosal tissue decreased, while the protein expression of SOX2 increased ( P<0.05). Conclusion:Jinbuhuan Jianwei Jiedu Decoction has a repairing effect on gastric function and mucosal lesions in CAG rats. Its mechanism may be related to the inhibition of abnormal activation of FXR/TGR5 pathway, regulation of bile acid and inflammatory mediator secretion.

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Objective:To compare the clinical efficacy and safety of hemoperfusion (HP) and gammaglobulin on the treatment of Henoch-Sch?nlein purpura (HSP) with gastrointestinal bleeding in children.Methods:Case-control study.A total of 39 HSP children combined with gastrointestinal bleeding diagnosed in the Department of Pediatric Nephrology, Rheumatology and Immunology, Shengjing Hospital of China Medical University from January 2015 to December 2019 were retrospectively recruited.They were divided into the HP group and the gammaglobulin group according to the therapeutic strategy.Clinical data were collected, and a 6-month follow-up survey was conducted for monitoring the relapse of gastrointestinal bleeding and the occurrence of kidney injury.The differences between groups were compared by Fisher′s exact test, two independent samples t-test, Mann-Whitney U-test, Kruskal-Wallis H-test, and One-Way ANOVA. Results:(1) There were 20 cases in the HP group and 19 cases were included in the gammaglobulin group.The gammaglobulin group was younger than the HP treatment group.(2) In addition to gastrointestinal bleeding, children in both groups had other clinical symptoms, such as abdominal pain, angioneurotic edema, and hematuria.(3)Comparison of laboratory indexes: Inflammatory indexes: white blood cell count (WBC), C-creative protein (CRP) and coagulation function indexes: fibrin degradation products (FDP), D-dimer (DD) were significantly elevated before treatment in the 2 groups, and there was no difference between the 2 groups ( P>0.05); WBC, CRP and FDP, DD declined in the 2 groups after treatment compared with the former, and there was no difference between the 2 groups ( P>0.05); (4) Comparison of clinical manifestations: when HP was applied with gammaglobulin in the treatment window within 3 d, the difference in the time of abdominal pain relief in the HP group was shorter than that of the gammaglobulin group [1.00(1.00, 1.00) d vs.2.00(1.75, 6.50) d, P=0.011]; comparing the time of gastrointestinal bleeding stopping when HP was applied with gammaglobulin comparison, the difference in gastrointestinal bleeding cessation time was not statistically significant ( P>0.05); (5) Comparison of hospitalization time: within 3 d application of HP compared with other window period hospitalization time were significantly reduced [(16.89±4.99) d than (19.20±2.39) d than (34.83±8.40) d, both P<0.05]; (6) Comparison of hospitalization costs: within 3 d application of HP compared with other window period hospitalization costs were significantly reduced [25 554.03 (22 168.61, 28 527.30) yuan than 33 619.48 (32 661.18, 36 971.47) yuan than 51 290.34 (34 163.04, 64 772.66) yuan, both P<0.05]; There were no statistically significant difference in the hospitalization time and hospitalization cost between and within the gammaglobulin group (all P>0.05); (7) Comparison of hormone dosages: the difference in the results of the initial dose of hormone use, pre-treatment dose of gammaglobulin/HP, and post-treatment dose of gammaglobulin/HP between the two groups of children was not statistically significant(all P>0.05). Safety profile was comparable between groups.The difference in hormone dosage before and after treatment within the gammaglobulin and HP treatment group was statistically different ( P<0.001). Conclusions:For children with severe HSP accompanied by gastrointestinal bleeding, early treatment with blood purification can rapidly relieve clinical symptoms and reduce the number of hospital days and hospitalization costs.For cases where blood purification is not available or suitable, gammaglobulin treatment is another option.

OBJECTIVE To observe the clinical efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced liver cancer. METHODS Sixty patients with advanced liver cancer who were treated in our hospital from March 2020 to November 2021 were selected as the study subjects， and then were randomly divided into study group and control group， with 30 cases in each group. The control group was treated with Sorafenib tosylate tablets orally （0.4 g，bid）， and the study group was additionally given Camrelizumab for injection intravenously （200 mg， every 3 weeks） based on the control group； for all patients， the treatment was stopped until disease progression or intolerable side effects occurred. The clinical efficacy， progression-free survival （PFS）， total survival （OS） and 1-year survival rate of the two groups were compared， and the incidence of adverse reactions in two groups， and immune-related adverse reactions in the study group during treatment were recorded. RESULTS The objective remission rate of the study group was significantly higher than the control group （36.7% vs. 13.3%， P＜0.05）， and the median OS and median PFS were significantly longer than the control group （OS： 12.6 months vs. 7.9 months； PFS： 8.2 months vs. 5.3 months， P＜0.05）. There was no significant difference in the 1-year survival rate and the incidence of elevated aspartate aminotransferase and alanine aminotransferase， rash or pruritus， anorexia， diarrhea， fatigue and hypertension between the two groups （P＞0.05）. The adverse events immune-related in the study group mainly included 21 cases of reactive capillary hyperplasia （70.0%）， 6 cases of hypothyroidism （20.0%）， and 1 case of immune-associated pneumonia （3.3%）， which were improved or tolerable after symptomatic treatment. CONCLUSIONS Camrelizumab combined with sorafenib in the treatment of advanced liver cancer can effectively control and delay the disease progression， prolong the survival period of patients， and the adverse reactions can be tolerated.

BACKGROUND:Sepsis-induced systemic inflammation leads to rapid bone mass loss;however,there is a lack of effective treatments.Ulinastatin is an anti-inflammatory drug,but its protective effect and mechanism on bone under sepsis-induced systemic inflammation are still unclear. OBJECTIVE:To explore whether ulinastatin can relieve acute bone loss caused by lipopolysaccharide. METHODS:(1)Animal experiment.Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group):control group,model group and experimental group.The control group was injected intraperitoneally with normal saline,the model group was injected intraperitoneally with lipopolysaccharide,and the experimental group was injected intraperitoneally with lipopolysaccharide and ulinastatin.In the experimental group,ulinastatin was injected continuously for 3 days.After intraperitoneal injection of ulinastatin for 14 days,femoral tissues were taken for CT scanning and pathological observation.(2)Cell experiment.C57BL/6 mouse primary osteoblasts were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide with ulinastatin was added to the experimental group.Cell proliferation and osteogenic differentiation were detected.C57BL/6 mouse bone marrow mononuclear cells were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide and ulinastatin were added to the experimental group.Osteoclast differentiation was detected. RESULTS AND CONCLUSION:(1)Animal experiment.CT scanning and hematoxylin-eosin staining showed that bone mass in lipopolysaccharide-treated mice was reduced but increased after treatment with ulinastatin.Tartrate resistant acid phosphatase staining showed that the number of osteoclasts in bone tissue increased in the model group,but significantly decreased in the experimental group compared with the model group.(2)Cell experiment.Cell counting kit-8 assay showed that lipopolysaccharide treatment inhibited the proliferation of osteoblasts,and ulinastatin elevated the proliferation of osteoblasts after lipopolysaccharide treatment.Alkaline phosphatase staining,alizarin red staining and osteogenesis-related gene(alkaline phosphatase,Runx2,osteocalcin,osteoblastin,nuclear factor κB receptor-activating factor ligand,osteoprotegerin)detection showed that lipopolysaccharide treatment inhibited osteogenic differentiation of osteoblasts and elevated the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio;ulinastatin did not have any significant effect on the reduction of osteoblast function induced by lipopolysaccharide but decreased the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio.Tartrate resistant acid phosphatase staining and osteoclast-related gene(tartrate resistant acid phosphatase and matrix metalloproteinase 9)detection showed that lipopolysaccharide treatment could promote osteoclast differentiation of bone marrow monocytes,while ulinastatin could inhibit lipopolysaccharide-induced osteoclast differentiation of bone marrow monocytes.(3)Overall,ulinastatin can significantly inhibit lipopolysaccharide-induced bone loss,mainly through promoting osteoblast proliferation and directly or indirectly inhibiting osteoclast differentiation to alleviate bone loss and achieve osteoprotective effects.

Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.

OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

  Objective  To explore the effect of esketamine on working memory impairment in neuropathic mice and its underlying mechanism.  Methods  Fifty clean grade male C57BL/6J mice (2 months) were divided into 5 groups by random number table method: sham+saline (SN group), CCI+saline (CN group), CCI+esketamine(CE group), CCI+ANA-12 (CA group), CCI+ANA-12+esketamine (CAE group), with 10 mice in each group. Chronic constriction injury (CCI) was employed to establish a neuropathic pain model. On the 16th day after modeling, CE group and CAE group were administered ketamine (10 mg/kg), CAE group received ANA-12 (0.5 mg/kg) half an hour before ketamine injection, CA group was only given ANA-12, and SN group and CN group received an equivalent volume of saline. The administration was done through intraperitoneal injection for 5 consecutive days. The open-field test (OFT), paw withdrawal threshold (PWT), paw withdrawal latency (PWL) and Y-maze test were performed from day 21 after surgery. Bromo-2-deoxyUridine (BrdU) was dissolved in saline and intraperitoneally injected into the mice on days 21 to 23 after the surgery. Western blot was performed to determine the expression of Brain-derived neurotrophic factor(BDNF) in hippocampus, the immunofluorescence was performed to determine the number of BrdU and doublecortxin (DCX) positive cells in the dentate gyrus (DG) area of hippocampal.  Results  Compared with SN group, the other four groups showed significant reductions in both PWT and PWL on day 21 after surgery (all P<0.05); There was no significant difference in the total distance travelled by the 5 groups of mice (P=0.142); In the Y maze test, compared to SN group, the accurate percentage of spontaneous alternation in CN group showed significant reductions (P<0.001), which was reversed by esketamine administration (P<0.001); compared with CE group, there was a significant reduction of the accurate percentage of spontaneous alternation in CAE group (P=0.004). The expression of BDNF protein in CN group was lower than that in SN group (P=0.021) and CE group (P=0.030), and compared with CE group, the expression of BDNF was significant decreased in CEA group (P=0.043). The number of BrdU positive and DCX positive cells significantly reduced in the DG area of the hippocampus in CN group compared to SN group (P=0.025) and CE group (P=0.003). The number of BrdU positive and DCX positive cells in CAE group significantly reduced in the DG region of the hippocampus compared to CE group (P=0.014).  Conclusion  Esketamine maybe improve working memory impairment in neuropathic mice and the neurogenesis in dentate gyrus area of hippocampal through the BDNF-TrkB pathway.