The off-label drugs use is a common practice in clinical medicine,which has both medical ethical legitimacy and ethical confusion,as well as hidden medical and legal risks.Appropriate the off-label drugs use can alleviate patients'pain,otherwise endangering their safety.The new Physician Law establishes legal norms for the off-label drugs use.The medical ethics and health law knowledge learned by resident physicians during their undergraduate studies all are basic knowledge and general principles,while the legal and ethical knowledge about the off-label drugs use is insufficient.A questionnaire survey on the ethical and legal issues of the off-label drugs use for resident physicians found that resident physicians urgently need to learn ethical and legal knowledge,as well as receive clinical application teaching and training in the aspect of the off-label drugs use.Therefore,in the standardized training of resident physicians,ethical and legal education on the off-label drugs use has been added.The core of this training is to conduct theoretical lectures focusing on the six ethical and legal principles of the off-label drugs use,as well as providing practical teaching drawing on the"clinic-style legal teaching"model.This paper explored a method for conducting ethical and legal education on the off-label drugs use in the future during the resident training stage.

Objective:To investigate the influencing factors of urinary system symptoms in urban and rural residents aged 35 years old and above in Anhui province.Methods:A total of 19 339 residents aged 35 years old and above were selected from 19 counties(districts)of 9 cities in Anhui Province by multi-stage stratified cluster random sampling method.Binary logistic regression was used to analyze the influencing factors of urinary system symptoms.Results:There were statistically significant differences among different gender,age,long-term residence,body mass index and education level in the other 3 symptoms except urinary secretions(P＜0.05).Binary logistic regression analysis model showed that with the increase of age,the risk of frequent urination/urgent urination/painful urination,eyelid or lower limb edema increased,OR values were all＞1.Body mass index≥24 kg/m2 was the risk factor of frequent urination/urgent urination/painful urination,eyelid or lower limb edema(P＜0.05).People who lived in rural areas for a long time had a lower risk of blood urination(OR=0.79,P＜0.05).The risk of urinary secretions decreased with the improvement of education level(P＜0.05).Diagnosed diabetes,use of analgesics(ibuprofen/butazon/indola,etc.),heavy dietary taste was(like to eat pickled/smoked/fried/spicy food),long-term heavy physical work(carrying heavy objects/digging/clearing snow/chopping wood,etc.),and sleep time＜8 h were the risk factors of these four urinary symptoms(P＜0.05).Long-term drinking was a risk factor for frequent urination/urgent urination/painful urination symptoms(OR=1.02,P＜0.05).Conclusion:Personal characteristics,diabetes mellitus,dietary habits,medication history and physical activity have a certain influence on the occurrence of urinary system symptoms.

Objective:To investigate the efficacy and safety of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM).Methods:The clinical data of 64 MM patients who received ASCT in the Second Affiliated Hospital of Xi'an Jiaotong University from October 2015 to March 2022 were retrospectively analyzed. The clinical characteristics, therapeutic effects and adverse reactions of the patients were summarized.Results:Of the 64 patients, 42 were male and 22 were female; the median age was 54 years old (37-69 years old). The median number of CD34 + cells collected from 46 patients in the CE (cyclophosphamide, etoposide) regimen mobilization group and 17 patients in the plerixafor mobilization group were 7.50×10 6/kg [(1.15-24.73)×10 6/kg] and 4.54×10 6/kg [(0.75-10.40)×10 6/kg], and the difference was statistically significant ( Z = 3.02, P = 0.024). Hematopoietic reconstitution was successful in all 64 patients, and the median time for white blood cell and platelet engraftment was 11 d (8-13 d) and 11 d (8-15 d), respectively. The patients' pretreatment regimens were all high-dose melphalan, the median white blood cell and platelet engraftment time of 29 patients in the oral group were 11 d (8-13 d) and 11 d (8-15 d), respectively, the median white blood cell and platelet engraftment time of 35 patients in the intravenous infusion group were 11 d (8-12 d) and 11 d (8-15 d), respectively, and there were no statistical differences (both P > 0.05). The ≥CR rate was 48.4% (31/64) before transplantation and 70.3% (45/64) three months after transplantation, and the difference was statistically significant ( χ2 = 6.35, P = 0.012). The median follow-up time of all patients was 27 months (2-67 months). The 3-year OS and PFS rates were 77.6% and 54.9%, and the median OS and PFS time were 67 and 52 months. The median hospitalization time was 20 d (15-37 d). There was no transplantation-related mortality, and the main adverse reactions were gastrointestinal reactions (100.0%, 64/64), grade 4 thrombocytopenia (98.4%, 63/64), grade 4 neutropenia, and agranulocytosis with fever (40.6%, 26/64). Conclusions:ASCT is effective for MM patients suitable for transplantation, which can further improve the remission rate and remission depth, prolong the PFS and OS time of patients, and the adverse reactions are controllable.

Objective:To analyze the effects of electrical acoustic stimulation (EAS) on speech and tone recognition as well as music perception in children with low-frequency residual hearing (LFRH) after cochlear implant (CI).Methods:A total of twelve Mandarin patients with LFRH who underwent unilateral CI from January 2017 to October 2020 were recruited, including 8 males and 4 females. There were 5 cases of pre-lingual deafness and 7 cases of post-lingual deafness. The median age at implantation was 12 years old (3-62 years). All patients had residual hearing (RH) before surgery, wore hearing aid (HA) timely, had an effective rehabilitation and the duration of use of electrical stimulation was 37.0±16.2 months. On the implanted side, the thresholds of 125 Hz and 250 Hz were less than and equal to 80 dB HL after implantation. A two-month follow-up clinical study was conducted with the EAS devices. The EAS effects were evaluated before, immediately after and 2 months after upgrade, including speech recognition rate, tone recognition and music tests. SPSS 23.0 software was used for statistical analysis.Results:A total of ten patients completed a two-month clinical follow-up and efficiency evaluation. Compared to the electrical stimulation, the recognition rate of spondee word significantly decreased after the immediate use of EAS (71.7±4.3 vs 79.6±3.1, P=0.018). Compared to the electrical stimulation as well as immediate use of EAS, the results of sentence in noise, tone in noise, and SRT of sentence in noise were all significantly improved at 2 months after use of EAS ( P<0.05). The pitch discrimination was significantly improved at 2 months after the use of EAS compared with that before the use of EAS ( P=0.042). Compared with before ( P=0.021) and immediately ( P=0.017) use of EAS, the ability of rhythm resolution was significantly improved. There were no significant differences in other test results ( P>0.05). Conclusions:The low-frequency acoustic information provided by EAS as well as the electrical-acoustic stimulation mode can provide rich auditory cues of speech perception in noise, tone recognition in noise, and musical discrimination for CI subjects. It can promote the improvement of complex listening ability of CI patients undergoing long-term electrical stimulation in a short time and comprehensively improve their hearing capacities.

Background:The musk glands of adult male Chinese forest musk deer(Moschus berezovskii Flerov,1929)(FMD),which are considered as special skin glands,secrete a mixture of sebum,lipids,and proteins into the musk pod.Together,these components form musk,which plays an important role in attracting females during the breeding season.However,the relationship between the musk glands and skin of Chinese FMD remains undiscovered.Here,the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing(RNA-seq),and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin.Methods:A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted.Then,based on the anatomical structure of the musk gland,skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD.These tissues were used for RNA-seq,hematoxylin-eosin(HE)staining,immunohistochemistry(IHC),western blot(WB),and quantitative real-time polymerase chain reaction(qRT-PCR)experiments.Results:Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod,while juvenile FMD did not have any well-developed musk pods.Transcriptomic data revealed that 88.24%of genes were co-expressed in the skin and musk gland tissues.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis found that the genes co-expressed in the abdomen skin,back skin,and musk gland were enriched in biological development,endocrine system,lipid metabolism,and other pathways.Gene Ontology(GO)enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division.Moreover,the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific.qRT-PCR and WB revealed that sex-determining region Y-box protein 9(Sox9),Caveolin-1(Cav-1),and androgen receptor(AR)were expressed in all three tissues,although the expression levels differed among the tissues.According to the IHC results,Sox9 and AR were expressed in the nuclei of sebaceous gland,hair follicle,and musk gland cells,whereas Cav-1 was expressed in the cell membrane.Conclusions:The musk gland of Chinese FMD may be a derivative of skin tissue,and Sox9,Cav-1,and AR may play significant roles in musk gland development.

Objective:To explore the effect of diet intervention based on information-motivation-behavioral skill (IMB) model in patients with diabetes combined with gout.Methods:From January 2019 to September 2021, diabetes patients with gout admitted to the Hangzhou First People's Hospital were selected by convenience sampling. According to the random number table method, patients were divided into a control group (60 cases) and a study group (60 cases). Both groups received symptomatic treatment and routine nursing. On this basis, the control group received routine diet intervention, while the research group received diet intervention based on the IMB model. The Diet Compliance Questionnaire and the Chinese version of the World Health Organization Quality of Life Measurement Scale-Brief Version (WHOQOL-BREF) were used to evaluate the diet compliance and quality of life of two groups of patients. This study measured the blood uric acid, glycosylated hemoglobin (HbA1c), and fasting blood glucose (FPG) in two groups of patients to evaluate their health condition.Results:After intervention, the scores of knowledge, attitude and practice dimensions in the Diet Compliance Questionnaire of patients in the study group were higher than those in the control group, and the Chinese version of WHOQOL-BREF score was higher than that in the control group, with statistical differences ( P<0.05). After intervention, the blood uric acid, FPG, and HbA1c in the study group were lower than those in the control group, with statistically significant differences ( P<0.05) . Conclusions:The diet intervention based on IMB model can improve the diet compliance of diabetes patients with gout, reduce the blood glucose and uric acid of patients, and improve the quality of life of patients.

Objective:To analyze the clinical curative effect of protective sleep nursing on neonatal hyperbilirubinemia.Methods:Eight neonates with hyperbilirubinemia who were admitted from April 2019 to August 2019 were enrolled. They were divided into control group (40 cases) and observation group (40 cases) by random digits table method. Both groups were given routine nursing. On basis of control group, observation group was given protective sleep nursing. The clinical effect, sleep time, discomfort reactions and nursing satisfaction were compared between the two groups.Results:After nursing, the sleep time, crying time and bilirubin level were (18.67 ± 1.45) h/d, (0.82 ± 0.12) h/d, (191.58 ± 12.74) μmol/L in the observation group, and (17.63 ± 1.33) h/d, (1.05 ± 0.15) h/d, (202.42 ± 13.08) μmol/L in the control group, there were significant differences between the two groups ( t values were 3.343, 7.573, 3.755, P<0.05). The duration and regression time of jaundice were (5.26±1.24), (8.70±2.12) d in the observation group, and (7.14±1.18), (12.95±2.31) d in the control group, there were significant differences between the two groups ( t values were 6.946, 8.573, P<0.05). The good rate of sleep quality, incidence rates of vomiting, skin damage and needle falling out, and nursing satisfaction rate were 90.00%(36/40), 7.50%(3/40), 5.00%(2/40), 10.00%(4/40), 100.00%(40/40) in the observation group, and 72.50% (29/40), 27.50%(11/40), 22.50%(9/40), 32.50%(13/40), 87.50%(35/40) in the control group, there were significant differences between the two groups ( χ2 values were 4.021-6.050, P<0.05). Conclusions:The application of protective sleep nursing in treatment of neonatal hyperbilirubinemia can effectively prolong their sleep time, improve their sleep quality, which is conducive to improving their symptoms, reducing discomfort reactions.And satisfaction of their family members is relatively higher.

Objective:To evaluate the influence of goal-directed volume management based on cardiac output index (CI), intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI) in patients undergoing off-pump coronary artery bypass surgery.Methods:Forty patients (ASA 2 to 3 grade) undergoing off-pump coronary artery bypass surgery in Lanzhou University Second Hospital from January 2017 to December 2018 were selected. The patients were divided into 2 groups by random digits table method with 20 cases in each group: study group (goal-directed fluid therapy treatment with CI, ITBVI and EVLWI) and control group (conventional fluid therapy). The control group was given central venous pressure (CVP) monitoring rehydration, and the study group was given PiCCO hemodynamic monitoring indicators. The CVP, CI, ITBVI and EVLWI for fluid management were measured. Accurate assessment of volume status of patients was done. The study group received goal-directed fluid therapy based on CVP, CI, ITBVI and EVLWI, with the goal of CI in the 3.0 to 5.0 L/(min·m 2) range, ITBVI in the 800 to 1 000 ml/m 2 range and EVLWI in the 3.0 to 7.0 ml/kg range. The heart rate, mean arterial pressure (MAP), urine volume, central venous oxygen saturation (ScvO 2), lactic acid and renal function were monitored. The ventilator withdrawal time, hospitalization in ICU, length of stay, incidence of acute pulmonary edema, incidence of acute renal failure, mortality of 30 d after surgery were recorded and compared between the two groups. Results:Tissue perfusion and urine volume of the study group was significantly improved compared with that of control group ( P<0.05). ScvO 2 of the study group was higher than that of the routine group ( P<0.05). The concentration of lactic acid of the study group was lower than that of the routine group ( P<0.05). The incidences of acute pulmonary edema, acute renal insufficiency and mortality of the study group were lower than those of the routine group (5.0% vs. 15.0%, 5.0% vs. 10.0% and 5.0% vs. 15.0%), and there were statistical differences ( P<0.05). The length of stay and hospitalization in ICU were both lower than those in the control group ( P<0.01). Conclusions:Goal-directed fluid therapy based on CI, ITBVI and EVLWI can effectively optimize the cardiac preload of patients undergoing off-pump coronary artery bypass surgery, improve cardiac output, ensure microcirculation perfusion, maintain the balance of oxygen supply and demand, and reduce the incidence of complications and mortality.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Objective To evaluate the effectiveness of a comprehensive hypertension management. Methods Hypertensive patients aged≥35 years in the Zhengfei community of Zhengzhou were selected. The patients were randomly assigned to the intervention and control groups. Those in intervention group received comprehensive hypertension management from October 2015 to September 2016,whereas those in the control group received the original management mode. Scales to assess blood pressure control, biochemical indexes, unhealthy lifestyle, and cardiovascular disease associated risk level were used to evaluate the effectiveness of the management modes.Results Each study groups had 1 051 patients.There were no significant differences in the baseline data of the two groups (P>0.05). At the end of 1 year of receiving the respective hypertension management modes, each group had 941 patients. Findings revealed that after receiving the comprehensive hypertension management mode, the systolic and diastolic blood pressure in the intervention group decreased by(9.87±7.38)mmHg(1 mmHg=0.133 kPa)and(6.33±4.14) mmHg,respectively.Those in the control group decreased by(7.01±6.02)mmHg and(4.52±3.59)mmHg, respectively,statistically significant differences in the extent of reduction of blood pressure between the two groups (P<0.05). Further, the fasting plasma glucose, postprandial blood glucose, low density lipoprotein, serum creatinine,and microalbuminuria levels in the intervention group were significantly lower than those in the control group(all P<0.05).However,the intervention group exhibited a significant increase in the high density lipoprotein level as compared to the control group(P<0.05).There were no significant differences in the total cholesterol,triglyceride,urinary creatinine levels,and body mass index between the two groups(P>0.05), although they had decreased in both groups. After the 1-year management, these proportions of smoking,heavy drinking,high salt diet and need to exercise were 10.0%,3.7%,20.1%,and 48.9% in the intervention group, and 15.3%, 10.0%, 29.0%, and 54.3% in the control group. The proportions were significantly different between the two groups (P<0.05). After the 1-year management, these proportions of low,moderate,and high risk of cardiovascular disease were 13.3%,33.5%,and 53.2% in the intervention group, and 11.2%, 30.1%, and 58.8% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). After the 1-year management, the proportion of treated, controlled, and control-treated hypertension using medication was 100%, 65.1%, and 75.3% in the intervention group, and 39.5%, 60.3%, and 70.0% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). Conclusion The comprehensive hypertension management mode was effective in significantly improving the blood pressure and health condition of hypertensive patients.