OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Ischemic stroke(IS)is a devastating neurological disease commonly around the world.Although modern medicine has recognized the confined mechanisms in the pathological process of cerebral ischemia,it has never been enough for the treatment of IS.Recent studies have confirmed the vital role of mitochondrial dysfunction in neuronal injury after cerebral ische-mia,thereby exerting a potential target for prevention and treat-ment of IS.Herein,we review the main molecular mechanisms of neuronal injury and death by mitochondrial dyshomeostasis under the condition of ischemia/hypoxia,especially mitochon-drial permeability transition pore opening,oxidative stress and apoptotic signaling.Given remodeling of mitochondrial function as a new idea for the management of IS,some emerging strate-gies containing mitochondrial antioxidant,mitophagy regulation and mitochondrial transfer also raise concern in this paper.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

OBJECTIVE: To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery. METHODS: A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group. RESULTS: In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05). CONCLUSION EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.
Humans ; Electroacupuncture ; Hemorrhoids/surgery* ; Urination ; Postoperative Nausea and Vomiting ; Acupuncture Points

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

Objective: To explore the effect of deep dermal tissue dislocation injury on skin fibrosis in pig, in order to provide some theoretical basis for burn scar treatment. Methods: The experimental research method was applied. Six 2-month-old female Duroc pigs were taken. Fifteen operative areas on the right dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and re-implanted were included into dermal in situ reimplantation group, and fifteen operative areas on the left dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and the deep dermal tissue slice was placed under the fat layer were included into the dermal dislocation group. The hair growth in the operative areas on post-injury day (PID) 7, 14, and 21 and the cross-sectional structure on PID 14 were observed in the two groups. On PID 7, 14, and 21, the skin thickness (the distance from the epidermis to the upper edge of the fat), the dermal thickness (the distance from the lower edge of the epidermis to the upper edge of the fat, excluding the fibrotic tissue thickness between the dermis and the fat), and the fibrosis tissue thickness of the dermis-fat interface (from the lower edge of the deep dermis to the upper edge of the fat in dermal in situ reimplantation group and from the lower edge of the superficial dermis to the upper edge of the fat in dermal dislocation group) in the operative areas were measured and compared between the two groups; the fibrotic tissue thickness at the dermal cutting interface (from the lower edge of the superficial dermis to the upper edge of the deep dermis) in the operative areas in dermal in situ reimplantation group was measured and compared with the fibrotic tissue thickness at the dermal-fat interface. Sirius red staining was performed to observe and compare the type Ⅰ and Ⅲ collagen content in the dermal-fat interface in the operative areas between the 2 groups and between the dermal cutting interface and dermal-fat interface in the operative areas in dermal in situ reimplantation group. Immunohistochemical staining was performed to observe the positive expressions of proliferating cell nuclear antigen (PCNA), transforming growth factor β₁ (TGF-β₁), fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HGF) in the operative areas in the two groups. The sample number was 6. Data were statistically analyzed with independent sample t test. Results: On PID 7, 14, and 21, the hairs in the operative areas in dermal in situ reimplantation group were denser than those in dermal dislocation group. On PID 14, the skin cross section in the operative areas in dermal dislocation group showed a "sandwich"-like structure, while the skin cross section in the operative areas in dermal in situ reimplantation group had normal structure. On PID 7, 14, and 21, the skin thickness in the operative areas in dermal dislocation group was (4 234±186), (4 688±360), and (4 548±360) μm, respectively, which was close to (4 425±156), (4 714±141), and (4 310±473) μm in dermal in situ reimplantation group (P>0.05); the dermal thickness in the operative areas in dermal dislocation group was significantly thinner than that in dermal in situ reimplantation group (with t values of -9.73, -15.85, and -15.41, respectively, P<0.01); the fibrotic tissue thickness at the dermal-fat interface in the operative areas in dermal dislocation group was significantly thicker than that in dermal in situ reimplantation group (with t values of 14.48, 20.58, and 15.67, respectively, P<0.01); there was no statistically significant difference between the fibrotic tissue thickness at the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, 21, the type Ⅲ collagen content in the dermal-fat interface in the operative areas in dermal dislocation group was increased significantly compared with that in dermal in situ replantation group (with t values of 2.65, 0.61, and 7.39, respectively, P<0.05 or P<0.01), whereas there were no statistically significant differences in the type Ⅰ collagen content at the dermal-fat interface in the operative areas between the 2 groups (P>0.05) and the type Ⅰ and Ⅲ collagen content between the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, and 21, PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis and adipose tissue in the operative areas in dermal dislocation group, while PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis, deep dermis, and adipose tissue in the operative areas in dermal in situ reimplantation group. Conclusions: Inadequate intrinsic thickness of dermal tissue is the key factor causing fibrosis, and the biological purpose of fibrosis is to "compensate" the intrinsic thickness of the skin. Besides, adipose tissue may also be an important component of fibrotic skin repair.
Swine ; Female ; Animals ; Dermis/pathology* ; Proliferating Cell Nuclear Antigen/metabolism* ; Fibroblast Growth Factor 2 ; Cross-Sectional Studies ; Fibrosis ; Skin Diseases/pathology* ; Collagen/metabolism*

Objective To observe the distribution of mesencephalic astrocyte derived neurotrophic factor (MANF) within the brain in human, mice and rats and the comparison across the species. Methods An immunohistochemical method was applied to investigate the expression of MANF and to compare the differences among species in the brain of human specimens ( n = 5) , mice ( n = 6) , and rats ( n = 6). Results The expression of MANF varied in different brain regions in human, mice and rats. In human, in the cortex, the expression of MANF was the highest among all brain regions. In the subcortical areas or the nucleus, brainstem and cerebellum expression level of MANF were relatively lower. The distribution of MANF in mouse and rat brain were slightly different from that in human brain, but generally consistent. Conclusion The distribution pattern of MANF is similar across the species, however, within a species, MANF expression levels varies in different brain regions.