Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

OBJECTIVE: To investigate the synergistic interaction between the deltoid muscle and the rotator cuff muscle group in patients with rotator cuff tears (RCT), as well as the impact of the critical shoulder angle (CSA) on deltoid muscle strength. METHODS: A retrospective analysis was conducted on clinical data from 42 RCT patients who met the selection criteria and were treated between March 2022 and March 2023. There were 13 males and 29 females, with an age range of 42-77 years (mean, 60.5 years). Preoperative visual analogue scale (VAS) score was 6.0±1.6. CSA measurements were obtained from standard anteroposterior X-ray films before operation, and patients were divided into two groups based on CSA measurements: CSA>35° group (group A) and CSA≤35° group (group B). Handheld dynamometry was used to measure the muscle strength of various muscle group in the shoulder (including the supraspinatus, infraspinatus, subscapularis, and anterior, middle, and posterior bundles of the deltoid). The muscle strength of the unaffected side was compared to the affected side, and muscle imbalance indices were calculated. Muscle imbalance indices between male and female patients, dominant and non-dominant sides, and groups A and B were compared. Pearson correlation analysis was used to examine the relationship between muscle imbalance indices and CSA as well as VAS scores. RESULTS: Muscle strength in all muscle groups on the affected side was significantly lower than on the unaffected side ( P<0.05). The muscle imbalance indices for the supraspinatus, subscapularis, infraspinatus, and anterior, middle, and posterior bundles of the deltoid were 14.8%±24.4%, 5.9%±9.7%, 7.2% (0, 9.1%), 17.2% (5.9%, 26.9%), 8.3%±21.3%, and 10.2% (2.8%, 15.4%), respectively. The muscle imbalance indices of the anterior bundle of the deltoid, supraspinatus, and infraspinatus were significantly lower in male patients compared to female patients ( P<0.05); however, there was no significant difference in muscle imbalance indices among other muscle groups between male and female patients or between the dominant and non-dominant sides ( P>0.05). There was a positive correlation between the muscle imbalance indices of infraspinatus and VAS score ( P<0.05), and a positive correlation between CSA and the muscle imbalance indices of middle bundle of deltoid ( P<0.05). There was no correlation between the muscle imbalance indices of other muscle groups and VAS score or CSA ( P>0.05). Preoperative CSA ranged from 17.6° to 39.4°, with a mean of 31.1°. There were 9 cases in group A and 33 cases in group B. The muscle imbalance indices of the anterior bundle of the deltoid was significantly lower in group A compared to group B ( P<0.05), while there was no significant difference in muscle imbalance indices among other muscle groups between group A and group B ( P>0.05). CONCLUSION Patients with RCT have a phenomenon of deltoid muscle strength reduction, which is more pronounced in the population with a larger CSA.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Shoulder ; Rotator Cuff Injuries/surgery* ; Shoulder Joint/diagnostic imaging* ; Rotator Cuff/surgery* ; Muscle Strength ; Deltoid Muscle

Objective To study the feasibility of domestic single-port surgical robot assisted endoscopic system for partial nephrectomy,and analyze its safety in clinical partial nephrectomy based on experimental results Methods Three qualified experimental pigs were selected,two senior urological professors and a senior resident doctor used a domestic single-port surgical robot to perform partial nephrectomy on the left and right kidneys.Recorded the operation duration,hot ischemia duration,suture time,estimated blood loss,volume of renal parenchyma excision and other information.Results There were 8 wedge resection and 4 heminephrectomies.The kidney volume of wedge resection was(7.35±0.81)mL and the blood loss was(8.50±11.09)mL.The total operation time was(41.67±8.50)min,and the time of resection was(5.88±3.27)min and the stitching time was(11.75±2.82)min.The kidney volume of heminephrectomy was(24.30±2.18)mL,and the blood loss was(6.25±4.35)mL.The total operation time of heminephrectomy was(47.00±11.27)min,and the time of resection was(3.25±1.5)min and the stitching time was(10.00±5.25)min.No bleeding was observed on the wound after the Bull dog was released in all operations.There was no significant difference in operation time and blood loss between the heminephrectomy group and the wedge resection group.There was no significant difference in operation time or blood loss between the senior doctor group and the senior resident doctor group.The NASA-TLX scale was used to assess the degree of workload of the operator during surgical operations,and the results showed that none of the three surgeons had a high level of frustration.There were no adverse events related to the single-port surgical robot system during the operation.Conclusion It is safe and feasible for a domestic single-port surgical robot system to perform a partial nephrectomy.

Objective: To explore the mechanism of moxibustion for rheumatoid arthritis (RA) by observing the metabolite changes in urine using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis. Methods: Twenty-four rats were randomly divided into a control group, a model group, and a moxibustion group. Rats in the model and moxibustion groups were established as collagen-induced arthritis (CIA) models. The control and model groups did not receive any intervention; rats in the moxibustion group received moxibustion at Shenshu (BL23) and Zusanli (ST36). After three weeks of intervention, ankle joint, serum, and urine samples were collected for pathological examinations and metabolomic tests. Results: After moxibustion treatment, the CIA rats showed increased body mass, reduced swelling of the hind paws and arthritis score, decreased serum cytokine levels, and improved histopathological evaluation of the ankle joint. Twenty-four significantly altered metabolites were found, mainly involved in alanine metabolism, taurine and hypotaurine metabolism, tricarboxylic acid cycle, phenylalanine metabolism, tyrosine metabolism, and primary bile acid biosynthesis. These metabolites may serve as potential biomarkers for RA. Conclusion: Moxibustion can effectively resist inflammation in CIA rats. The potential biomarkers and the abnormal metabolic pathways of RA can be identified by LC-MS-based metabolomics. Metabolomics may be an effective way to explain the mechanism of moxibustion in treating RA.

Objective:To investigate the clinical characteristics, efficacy and prognostic influencing factors of IgD multiple myeloma (MM) in the new immunotherapy era.Methods:The clinical data of 29 patients diagnosed with IgD MM in the Affiliated Hospital of Xuzhou Medical University from March 2014 to February 2021 were retrospectively collected. The clinical characteristics, treatment regimens and efficacy, especially the efficacy of new drugs and immunotherapy for the disease were analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional risk model was used for analysis of prognostic influencing factors.Results:The median age of patients was 58 years. There were 20 cases (69.0%) below 65 years, 12 cases (41.4%) of complicated with stomach function damage, 6 cases (20.7%) of extramedullary invasion. All patients were treated with combined therapy containing proteasome inhibitor bortezomib in the first-line therapy, and the overall response rate was 82.8% (24/29). Among 21 relapsed/refractory patients, 12 patients were treated with the second-line or above treatment regimen chimeric antigen receptor T cell (CAR-T) immunotherapy, including 9 cases achieving very good partial remission (VGPR) or above; 5 patients were treated with the new drug daratozumab, including 1 case achieving complete remission (CR). The median OS time of 29 patients was 48 months (95% CI 17-79 months), the median PFS time after the first-line treatment was 9 months (95% CI 3-15 months), and the median PFS time after the second-line treatment was 11 months (95% CI 1-21 months). Multivariate Cox regression results showed that CAR-T therapy is an independent influencing factor of the prognosis of relapsed/ refractory IgD MM patients ( HR = 0.094, 95% CI 0.019-0.473, P = 0.004). Conclusions:IgD MM patients are characterized with lower onset age, more renal function damage and a high incidence of extramedullary invasion. The first-line therapy containing proteasome inhibitor has a better short-term efficacy, and CAR-T therapy can improve the remission rate and survival rate of relapsed/refractory IgD MM to a certain extent.

Objective:To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO 2/FiO 2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO 2, SpO 2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. Results:Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ β values were -15.827, 1.202, 95% confidence interval (95% CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. Conclusion:Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

Objective To investigate the CD47 expression in de novo acute myelogenous leukemia (AML) patients with normal karyotype and its clinical significance. Methods One hundred thirty-seven cases of de novo AML with normal karyotype and 3 healthy volunteers were selected. Relative CD47 expressions in normal bone marrow hematopoietic stem cells (HSC) and multipotent progenitor (MPP) from healthy volunteers, as well as bone marrow mononuclear cells (MNC) and leukemia stem cells (LSC, Lin-CD34+CD38-CD90-) from AML patients were determined by flow cytometry. CD47 expression on the Lin-CD34+CD38-LSC-enriched fraction of specimen was determined by flow cytometry. The FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) was detected by using the Genome Analyzer platform. CD34+CD38-CD47hi and CD34+CD38-CD47lo expressing cells were identified and purified using FACS. Two groups of cells were inoculated with MethoCult H4445 medium on agarose-containing methylcellulose plates. After 12 days, MPP colony forming units (CFU) were counted, and 1×105 CD34+ CD38- CD47lo and CD34+ CD38-CD47hi cells were transplanted into NSG (NOD-SCID IL-2R γ null) mice irradiated by 280 cGy, and mice were sacrificed after 8 weeks. The ratio of human CD45+cells was detected by flow cytometry. Results The expression of CD47 in AML patients was higher than that in the healthy control. CD47 was expressed in all FAB (French-American-British) subtypes of AML. No significant difference in CD47 expression among different FAB subtypes was found (F=0.545, P>0.05). Among the 37 patients with CD34+CD38-CD47hi, 17 (46 %) were FLT3-ITD negative, and 20 (54 %) were FLT3-ITD positive. Among the 100 patients with CD34+CD38-CD47hi, 63 (63%) cases were FLT3-ITD negative, 37 (37%) cases were FLT3-ITD positive. The rate of FLT3-ITD positive in patients with CD34+ CD38- CD47lo had no statistical difference compared with patients with CD34+CD38-CD47hi (χ2= 3.79, P> 3.79). The CD34+CD38-CD47lo or CD34+CD38-CD47hi which was selected by FACS, was inoculated with the methylcellulose plate containing agarose for 12 days, and CD34+CD38-CD47lo cells could form CFU. The NSG mouse transplantation experiment showed that CD34+CD38-CD47lo cells could be reconstructed hematopoiesis, and CD34+CD38-CD47hi implantation failed. Conclusion CD34+CD38-CD47hi could enrich LSC, which may be a potential marker to detect minimal residual disease.

Objective To compare the ameliorating effect of collagen peptide chelated calcium (CPCC) and estrogen on the bone quality in ovariectomized rats in order to serve the development of safe drugs for prevention of osteoporosis (OP).Methods Bilateral ovariectomized rats were divided into ovariectomized group (OVX),sham group,17β-estradiol injection group (OVX+E2) and CPCC gavage group (OVX+CCCP).Bone and serum indices of these groups were assessed and compared at 9 weeks after treatment.Results Bone density of the OVX group was significantly lower than the sham group (P<0.01),indicating that the rat OP model was successfully established.Like estrogen,CPCC inhibited the abnormal changes of all indices and maintain similar levels with those of the sham group (P>0.05),while the body weight gain of the E2 group at weeks 8 and 9 was significantly lower than those of the sham group (P<0.01).As regarding the prevention of bone loss,the Mg and Ca levels of the E2 group were significantly lower than those of the moderate and high dose CPCC groups.The Cu level was not significantly different compared with the sham group,while those in the moderate and low dose CPCC groups were significantly higher than the sham group.The Mn,Zn and hydroxyproline levels of the E2 group were significantly lower than those of the sham group,while the CPCC group maintained levels similar to that of the sham group.In regarding to the inhibiting effect on the increased blood BGP and StrACP,the E2 group was still maintained at levels similar to that of the OVX group,while those of the CPCC group were significantly lower than the OVX group.As regarding the decreased blood Ca,the E2 group was not significantly different with that of the OVX group,while that of the CPCC group was significantly higher than the OVX group.Conclusions CPCC is more effective than estrogen in ameliorating the bone quality of ovariectomized rats.