ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective:To investigate the effect and mechanism of Sufentanil (Suf) on oxidative stress injury in osteoporosis (OP) rats.Methods:Rats were randomly separated into normal group, OP group, low concentration Suf group, high concentration Suf group, alendronate sodium group, and high concentration Suf+AMPK inhibitor (Dorsomorphin) group, with 12 rats in each group. The normal group of rats only removed a small amount of adipose tissue around the ovaries. Except for the normal group, rats in other groups constructed OP models by removing both ovaries. After successful modeling, they were administered once a day for 12 weeks. Micro CT scanners were applied to measure bone density and trabecular structure parameters in rats, including trabecular quantity, trabecular thickness, and trabecular separation. ELISA was applied to detect levels of osteocalcin, alkaline phosphatase (ALP), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) in rat serum. HE staining was applied to detect pathological changes in femoral tissue. Reagent kit was applied to detect levels of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) in femoral tissue. Western blot analysis of phosphorylated adenylate activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), silence-information regulatory factor2-associated enzyme 1 (SIRT1) proteins in femur tissue.Results:Compared with the normal group, the bone trabecular structure of rats in the OP group was thin and scattered, with fewer bone trabeculae and widened trabecular gaps, mainly in the form of rods, the bone density, number of trabeculae, thickness of trabeculae, levels of ALP, osteocalcin, OPG in serum, the level of SOD, and p-AMPK, PGC-1α, and SIRT1 proteins in femoral tissue decreased ( q=38.00, 67.81, 47.91, 48.32, 28.42, 21.23, 52.22, 30.86, 24.11, 24.55, P all<0.001), the bone trabecular separation, level of RANKL in serum, and the levels of MDA and ROS in femoral tissue increased ( q=42.00, 37.97, 50.56, 72.01, P all<0.001). Compared with the OP group, the number of bone trabeculae in rats in the low concentration Suf group, high concentration Suf group, and alendronate sodium group increased, the gap decreased, and the bone trabecular structure gradually recovered to a plate-like shape, the bone density, number of trabeculae, thickness of trabeculae, levels of ALP, osteocalcin, OPG in serum, the level of SOD, and p-AMPK, PGC-1α, and SIRT1 proteins in femoral tissue increased ( F=214.40, 889.60, 396.10, 480.30, 168.60, 38.09, 367.80, 187.70, 91.17, 101.00, P all<0.001), the bone trabecular separation, level of RANKL in serum, and the levels of MDA and ROS in femoral tissue decreased ( F=174.10, 173.40, 298.90, 607.10, P all<0.001). Dorsomorphin reversed the improvement effect of high concentration of Suf on oxidative stress injury in OP rats. Conclusion:The inhibitory effect of Suf on oxidative stress injury in OP rats may be related to the activation of the AMPK/SIRT1/PGC-1α signaling pathway.

Objective:To explore the alterations in functional connectivity density (FCD) resulted from mild cognitive impairment (MCI) and their correlations with cognitive scores in various cognitive domains in patients with Parkinson's disease (PD).Methods:Forty-three PD patients admitted to Department of Neurology, Sixth Affiliated Hospital of Nantong University from January 2022 to April 2024 were selected and divided into PD-MCI group (MoCA scores<26) and PD with normal cognition (PD-NC) group (MoCA scores≥26) according to Montreal Cognitive Assessment (MoCA). Another 23 middle-aged and elderly healthy volunteers (HC group) matched with PD patients in age, gender and education level were recruited at the same period. Resting-state functional MRI (rs-fMRI) data were collected and whole brain FCD was calculated. Differences of clinical data, whole brain FCD, and FCD in brain regions with significantly different FCD among the 3 groups were compared. Efficiency of FCD in brain regions with significantly different FCD between PD-MCI group and PD-NC group in differentially diagnosing PD-MCI and PD-NC was analyzed by receiver operating characteristic (ROC) curve. Pearson correlation was used to the analyze the correlations of FCD in brain regions with significantly different FCD with MoCA score and cognitive scores in various cognitive domains.Results:Among the 43 patients, 23 were into the PD-MCI group and 20 into the PD-NC group. PD-MCI group had significantly lower scores in the visuospatial and executive function, abstraction, and delayed memory cognitive domains than PD-NC group ( P<0.05). Brain regions with significantly different FCD among the 3 groups were the right parahippocampal gyrus, left gyrus rectus, right rolandic operculum, left middle occipital gyrus, right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. Compared with the HC group, the PD-MCI group and PD-NC group had significantly increased FCD at the right parahippocampal gyrus, left gyrus rectus and right rolandic operculum, statistically decreased FCD at the right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus ( P<0.05). Compared with the HC group, the PD-MCI group had significantly increased FCD at the left middle occipital gyrus ( P<0.05). Compared with the PD-NC group, the PD-MCI group had significantly decreased FCD at the right parahippocampal gyrus, and statistically increased FCD at the left middle occipital gyrus and left middle frontal gyrus ( P<0.05). Area under ROC curve (AUC) of FCD in brain regions with significantly different FCD in discriminating PD-MCI and PD-NC was 0.878, with sensitivity of 90.0% and specificity of 91.3%. FCD at right parahippocampal gyrus, left middle occipital gyrus and left middle frontal gyrus was negatively correlated with MoCA score ( P<0.05); FCD at right parahippocampal gyrus was positively correlated with cognitive scores in the visuospatial and executive function, and delayed memory domains ( P<0.05); FCD at left middle occipital gyrus was negatively correlated with cognitive scores in the executive function and visual-spatial skills, and abstraction domains ( P<0.05); FCD at the left medial frontal gyrus was negatively correlated with cognitive scores in the visuospatial and executive function, abstraction and delayed memory domains ( P<0.05). Conclusions:Abnormal FCD can be noted in some brain regions of PD patients, enjoying differences between PD-MCI patients and PD-NC patients. Combined FCD in brain regions with significantly different FCD has high value in differentially diagnosing PD-MCI and PD-NC, and FCD in brain regions with significantly different FCD is correlated with cognitive function changes in PD patients.

Objective:To investigate the characteristics of anorectal dynamics in elderly patients with functional defecation disorders(FDD), and to provide a basis for their diagnosis, treatment and prevention.Methods:In this retrospective study, 226 patients with FDD receiving 3D high-resolution anorectal manometry were divided into an elderly group(93 cases)and a non-elderly group(133 cases). Results from anorectal manometry parameters were compared and analysis of patterns of anorectal pressure changes in elderly participants based on sex, the Bristol stool classification and clinical symptoms was conducted.Results:The resting anal pressure, rectal pressure and anal relaxation rate were lower( t=-3.407, -2.051, Z=2.548, P=0.001, 0.040, 0.011)and the volume of first sensation was higher( t=1.998, P=0.047)in the elderly group than in the non-elderly group.The maximum anal squeezing pressure, residual anal pressure and maximum tolerated volume were higher( t=4.589, 4.730, 2.025, all P<0.05), whereas the anal relaxation rate and anorectal pressure gradient were lower in elderly men than in elderly women( Z=4.059, t=-3.714, P<0.001 for both). Regarding the types of FDD, both the elderly group and the non-elderly group were dominated with type Ⅱ defecation disorder, with more men than women having type Ⅱ defecation disorder in the elderly group( χ2=10.343, P=0.001). In cases of paradoxical sphincter contraction during simulated defecation, the incidence in the elderly group was 80.65%(75/93), which was higher than 68.42%(91/133)in the non-elderly group( χ2=4.194, P=0.041). The volume of first sensation, volume of first defecation sensation, and maximum tolerated volume of patients in the elderly group without the urge to defecate were(59.86±23.84)ml, (96.76±34.61)ml, and(144.32±30.57)ml, respectively, higher than those of patients with the urge to defecate(46.79±17.20)ml, (75.26±28.75)ml, and(120.00±40.28)ml( t=-2.241, -2.493, -2.891, P=0.027, 0.014, 0.005). The rectal pressure(26.52±16.08)mmHg of patients with defecation dyssynergia was lower than that of patients without defecation dyssynergia(39.91±8.82)mmHg(1 mmHg=0.133 kPa)( t=-3.128, P=0.002), while the resting anal pressure of patients with defecation dyssynergia(90.60±28.44)mmHg was higher than that of patients without defecation dyssynergia(73.65±27.10)mmHg( t=-2.201, P=0.030). The resting anal pressure and maximum anal squeezing pressure in patients with anal blockage sensation[(87.11±24.64)mmHg, (149.28±48.29)mmHg]were higher than those in patients without anal blockage sensation[(72.43±20.02)mmHg, (121.76±26.35)mmHg]( t=2.954、3.066, P=0.004、0.003). There was no significant difference in values from parameters of anorectal dynamics between patients with different Bristol stool types, with and without incomplete defecation or with different degrees of abdominal distension(all P>0.05). Conclusions:Anorectal dynamics in patients with FDD are characterized by paradoxical anal sphincter movements, but older patients with FDD are mainly characterized by inadequate rectal propulsion, pelvic floor muscle dysfunction and reduced rectal sensitivity.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective:To analyze the characteristics of the ocular vestibular evoked myogenic potential on three different eye positions and to explore the appropriate eye position for oVEMP.Methods:15 patients (30 ears) with vertigo who underwent oVEMP test from December 2017 to May 2018 were selected as the patient group, including seven males and eight females, with an average age of (51±13) years. Another 22 (44 ears) healthy young people were recruited into the control group, including 10 males and 12 females, with an average age of (23±5) years. oVEMPs were measured on the following three eye positions respectively: 30 degrees straight up(upper median position),45 degrees upper right(upper right position), and 45 degrees upper left(upper left position). oVEMP elicitation rate, oVEMP latencies, amplitudes and interaural amplitude asymmetry ratio were analyzed by SPSS 23.0 statistical software.Results:There was no statistical significance ( P>0.05) in the oVEMP elicitation rate, oVEMP latency, amplitude and asymmetry ratio on the three eye positions among the control group, the patient group and the overall subjects. Conclusions:The three eye positions can be used to detect oVEMP in clinic. There is no difference in the extraction rate and waveform characteristics. When one of the eye positions is difficult to gaze or not easy to obtain the coincidence curve, the other two can be used to obtain the ideal oVEMP curves as well.

Objective: To study the feasibility of using a double purse-string bridging pancreaticojejunostomy in total laparoscopic pancreaticoduodenectomy (TLPD). Methods: A database of 35 patients who underwent TLPD using a double purse-string bridging pancreaticojejunostomy from January 2016 to January 2019 in Jinhua Hospital of Zhejiang University was retrospectively reviewed. The perioperative outcomes were analyzed. Results: All the 35 patients underwent TLPD successfully. The surgery time was (370.2±33.5) min, and the time of constructing the pancreaticojejunostomy was (28.4±12.6) min. The hospital stay after surgery was (14.2±6.9) days. Five patients developed postoperative complications, including pancreatic fistula in 3 patients, bile leakage in 1 patient, gastroparesis (complicated with abdominal infection) in 1 patient, and abdominal infection in 3 patients (2 patients with pancreatic fistula, and 1 patient with gastroparesis). All the patients with complications responded well to conservative treatment. Conclusions A double purse-string bridging pancreaticojejunostomy was simple and widely applicable. It is safe and feasible in total laparoscopic pancreaticoduodenectomy and should be promoted in clinical practice.

OBJECTIVE: To observe the clinical effects and safety on female depression treated with the combined therapy of acupuncture and the five-element music therapy. METHODS: A total of 120 female patients with depression were randomized into an electroacupuncture (EA) group, an acupuncture group, a five-element music therapy group and a group of the combined therapy of acupuncture and the five-element music therapy (combined therapy group), 30 cases in each one. In the EA group, the electric stimulation of acupuncture was applied at Baihui (GV 20), Shenting (GV 24), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6) and Taichong (LR 3), with disperse-dense wave, 10 Hz/50 Hz, and 0.5 ms in wavelength. The needles were retained for 30 min. In the acupuncture group, the acupoints were same as the EA group, but without electric stimulation. In the five-element music therapy group, the music of tune was adopted in the treatment. In the combined therapy group, the acupuncture treatment and the five-element music therapy were same as the acupuncture group and the five-element music therapy group, in which the music therapy was followed after acupuncture treatment. The treatment was given once a day, at 2 days of interval after every 5 treatments in a week, totally for 8 weeks. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) before and after treatment and the treatment emergent symptom scale (TESS) after treatment were observed in each group. The clinical effects and safety were compared among the groups. RESULTS: The total effective rate was 86.7% (26/30) in the combined therapy group, better than 66.7% (20/30) in the EA group, 63.3% (19/30) in the acupuncture group and 53.3% (16/30) in the five-element music therapy group (<0.01, <0.05). After treatment, HAMD and HAMA scores were all reduced obviously in the patients of the 4 groups (all <0.01), and the scores in the combined therapy group were lower than the other 3 groups (all <0.01). The TESS score in the combined therapy group was lower than the other 3 groups (all <0.01) and the score in the five-element music therapy group was lower than the EA group and the acupuncture group (both <0.01). CONCLUSION In the female patients, the combined treatment with acupuncture and the five-element music therapy obviously reduces the severity of depression and anxiety, as well as the adverse reactions. The effects are better than the simple application of EA, acupuncture or music therapy.
Acupuncture Therapy ; Depression ; therapy ; Electroacupuncture ; Female ; Humans ; Music Therapy