Abstract: Leprosy, as an important neglected tropical disease (NTDs), has a tremendous impact on the patients’body and psychology, families and society. In this paper, we reviewed the progress of epidemiology, genetic factors, immune mechanisms, diagnosis and treatment of leprosy, and introduced the changes of national prevention and control policies and the prevention and control process of Hainan Province, so as to improve the clinical understanding among healthcare professionals. According to the World Health Organization's (WHO) global annual leprosy situation report data, the number of new cases and the incidence rate of leprosy have been showing a downward trend worldwide. In China, the epidemic situation of leprosy remains in an overall low-endemic state. However, the long-standing low-endemic status of leprosy and its wide and uneven distribution pose challenges to the prevention and control of leprosy. The pathogenesis of leprosy is mainly related to skin barrier, immune deficiency, and related signaling pathways. Serological testing, cytokines, and microRNA markers can all be used to assist in the early diagnosis of leprosy, while also helping to distinguish different types of leprosy, predict leprosy reactions, evaluate efficacy, and monitor family contacts. The main treatment plan for leprosy involves combination chemotherapy with drugs recommended by the WHO, such as rifampicin, dapsone, clofazimine and other drugs. Currently, the main prevention and treatment strategies for leprosy are early detection, early diagnosis and early treatment, controlling the source of infection, protecting the healthy population, preventing the occurrence of deformity, and improving the quality of life after recovery. At present, Hainan Province as well as the whole country is in a low-epidemic state, but healthcare professionals still need to improve their awareness of prevention, reduce their incidence rate, and strive to achieve the goal of "zero leprosy" as soon as possible.

Objective:This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) .Methods:The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed.Results:A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM ( P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI ( RR=1.827, 95% CI 1.015-3.288, P=0.044) . Conclusion:In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

G protein-coupled receptors(GPCRs)represent the largest class of cell surface receptors,mediating wide range of cellular and physiological processes through their transducers,G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy(cryo-EM),leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution threedimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously,which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors,and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction,providing important information for understanding GPCR signaling and the structure-based drug design.
Cryoelectron Microscopy ; Protein Binding ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled ; chemistry

Objective To explore the effects and mechanism of microRNA-138 (miR-138) on brain glioma cells invasion and migration.Methods The expression of miR-138 was detected by real time quantitative polymcrase chain reaction (qRT-PCR) in 60 cases of glioma tissues and para-carcinoma tissues,and the relationship between miR-138 expression and glioma grading was analyzed.Human glioma cells line U87 and U251 were transfected with miR-138 mimic and negative control (miR-NC).The expression of miR-138 was detected by qRT-PCR.The migration and invasion abilities were tested by Transwell assay,and the expression of semaphoring 4C (Sema4C) protein was tested by Western blotting.Results The expression level of mniR-138 in glioma tissues (2.46 ± 1.07) was significantly lower than that in normal brain tissues (4.83 ±1.16,t =-11.631,P ＜0.001),and miR-138 expression was negatively correlated with tumor grade (r =-O.563,P =0.001).The expression level of miR-138 in cells was significantly higher after being transfected with miR-138 mimic (U251:3.96 ±0.16;U87:4.43 ±0.96) than miR-NC (U251:2.32 ±0.36;U87:2.58± 0.62,t =7.253,P ＜ 0.001;t =8.872,P ＜ 0.001).The ability of invasion and migration were lower after being transfected with miR-138 mimic (U251:89±9;U87:95 ± 10) than miR-NC (U251:206 ± 15;U87:240 ± 20,t =36.629,P ＜ 0.001;t =35.521,P ＜ 0.001).The expression of Sema4C protein was lower after being transfected with miR-138 mimic (U251:0.41 ± 0.06;U87:0.36-± 0.03) than miR-NC (U251:1.01±0.08;U87:1.03±0.13,t=-32.862,P＜0.001;t=-27.512,P＜0.001).Conclusion The up-regulated expression of miR-138 can suppress glioma cells migration and invasion,which might be related to the negative regulation expression of Sema4C protein.

Objective To explore the influence of intracranial pressure monitoring on GCS score,complications and prognosis of severe traumatic brain injury patients with trauma craniectomy.Methods A total of 84 patients with STBI were randomly divided into two groups.The routine group was treated with standard large trauma craniectomy,and monitoring group was treated with trauma craniectomy combined with intracranial pressure monitoring.The change of intra-carnial pressure before and after operation,GCS scores change,prognosis as well as post operative complications were compared between two groups.Results Compared with routine group,the intra-carnial pressure at 3rd and 7th day after operation in monitoring group significantly decreased (P<0.05),and the GCS score at 28th day improved after operation in both groups,and increasing degree of monitoring group was significantly higher than the routine group (P<0.05).The GCS score at 3rd month after operation indicated that the prognosis in monitoring group was significantly better than routine group (P<0.05).The incidence rates of electrolyte disturbance in monitoring group and routine group at 6 month after surgery were 59.5% and 33.3% respectively (P<0.05).Conclusion Standard trauma craniectomy combined with intracranial pressure monitoring treatment is effective in treatment of patients with severe traumatic brain injury.

Objective To explore the influence of intracranial pressure monitoring on GCS score,complications and prognosis of severe traumatic brain injury patients with trauma craniectomy.Methods A total of 84 patients with STBI were randomly divided into two groups.The routine group was treated with standard large trauma craniectomy,and monitoring group was treated with trauma craniectomy combined with intracranial pressure monitoring.The change of intra-carnial pressure before and after operation,GCS scores change,prognosis as well as post operative complications were compared between two groups.Results Compared with routine group,the intra-carnial pressure at 3rd and 7th day after operation in monitoring group significantly decreased (P<0.05),and the GCS score at 28th day improved after operation in both groups,and increasing degree of monitoring group was significantly higher than the routine group (P<0.05).The GCS score at 3rd month after operation indicated that the prognosis in monitoring group was significantly better than routine group (P<0.05).The incidence rates of electrolyte disturbance in monitoring group and routine group at 6 month after surgery were 59.5% and 33.3% respectively (P<0.05).Conclusion Standard trauma craniectomy combined with intracranial pressure monitoring treatment is effective in treatment of patients with severe traumatic brain injury.

Objective To investigate the relationship between occult pancreaticobiliary reflux (OPR) and biliary diseases.Methods Forty-four patients with primary biliary diseases was enrolled,and serum amylase level was determined,and the bile in common bile duct (CBD) was collected to measure the amylase level,then the △ amylase was calculated,which equals bile amylase level minus serum amylase level.OPR was confirmed if bile amylase level was higher than serum amylase level,otherwise it would be defined as the control group.Results Among the 44 patients with primary biliary diseases,the incidence of OPR was 72.7％ (n =32).The bile and serum amylase activity of patients with OPR were (1 513 ± 2 725),(44 ± 21)U/L;and they were (18 ± 14) and (38 ± 17) U/L in the control group.The bile amylase level in OPR group was significantly higher than that in the control group,and the difference was statistically significant (P ＜ 0.05),while there was no significant difference in serum amylase activity between the two groups.The incidence of OPR in patients with CBD stones was 100％,and the bile amylase activity was (1 048 ± 1 317) IU/L,and the △ bile amylase activity was (996 ± 1 322) U/L;the incidence of OPR in patients with choledocholithiasis and cholecystolithiasis was 75％,and the bile amylase activity was (2 457 ± 3 312),the △ amylase activity was (2 412 ± 3 320)IU/L;and the corresponding values in patients with gallbladder stones were 80％,(95 ± 82),(57 ± 76)IU/L;and the corresponding values in patients with bile duct cancer were 50％,(73 ± 51),(40 ± 37)U/L.Conclusions The occurrence of OPR is closely related to CBD stones only,CBD stones and gallbladder stones,and it may be one of the main pathogenic factors of bile duct stones.

OBJECTIVE:To investigate the therapeutic efficacy and safety of mycophenolate mofetil combined with glucocorti-coid in the treatment of refractory idiopathic thrombocytopenic purpura (ITP). METHODS:134 cases of refractory ITP were ran-domly divided into observation group and control group,with 67 cases in each group. Control group was given Prednison acetate tablet orally,0.5 mg/kg each day,morning and evening. Observation group was additionally given Mycophenolate mofetil dispers-ible tablet,1 g/time,bid. A treatment course lasted for 3 weeks,and both groups received 3-5 courses of treatment. Clinical effica-cy of 2 groups were compared as well as the change of PLT before and after treatment,satisfaction degree of treatment and adverse event. RESULTS:The total effective rate of observation group (91.04%) was significantly higher than that of control group (74.63%),with statistical significance(P<0.05);PLT of observation group was significantly greater than that of control group 7, 14 and 21 d after treatment,with statistical significance(P<0.05);total satisfactory degree of observation group was significantly higher than that of control group (89.55% vs. 80.60%),and the incidence of adverse event was significantly lower than control group(2.99% vs. 10.44%),with statistical significance(P<0.05). CONCLUSIONS:Mycophenolate mofetil combined with glu-cocorticoid can improve clinical efficacy,PLT and satisfactory degree significantly in the treatment of refractory ITP with good safety.

Objective To investigate the status quo of nursing lack in level three first-class hospitals of Zhongshan city,and analyze the relevant reasons.Methods A sample of 765 nurses in 4 tertiary general hospitals completed the modified Missed Nursing Care Survey.Results Assessment,planning,intervention and evaluation were reported to be missed by 9.86％～39.04％,12.05％～44.38％,3.29％～46.85％ and 12.19％～22.05％ of the survey respondents respectively.Reasons for missed care were lack of labor resources(85.48％～93.84％),lack of material resources(80.00％～80.96％),low efficiency of the team (78.08％～86.58％),poor work habits (70.95％～83.84％),and improvement of patients’ needs (88.90％～93.01％).Conclusions Lack of care is widespread,and the degree of lack of each link is different.Reasons lead to the lack of care of nursing staff are higher patients’ demands to nursing work,shortage of nursing staff and unplanned surge of patients’ number.

Objective To analyze the efficacy and safety of suprapubic arc sling (SPARC) and transobturater vaginal tape (TOT) for female stress urinary incontinence (SUI). Methods A retrospective study was conducted on 275 women ( 139 in TOT group and 136 in SPARC group) in our institute from September 2008 to January 2011.We had compared the complications of the two groups.All the patient's ICI-Q-SF scores and PISQ-12 scores were collected.We compared the pre- and post-operative Qmax and PVR to find out if SPARC or TOT tap cause bladder outlet obstruction (BOO). Results The operative time was 25.1 ± 3.3 min for TOT and 34.8 ± 5.6 min for SPARC.There was statistical difference between the two groups in the aspects of operative time (P =0.00).The improvements of average symptom and QOL scores in patients undergoing TOT and SPARC were statistically significant (P =0.00).The improvements of the PISQ-12 scores in the two groups were statistically significant (P ＜0.05 ) as well.There was no significant difference (P ＞ 0.05 ) in the total cure rate of TOT and SPARC.The complications post SPARC and TOT were low.In the TOT group,the Qmax changed from 30.2 ± 8.7 ml/s per-operatively to 24.9 ± 8.6 ml/s post-operatively in a week.PVR changed from 1.6 ± 4.2 ml pre-operatively to 3.2 ± 6.5 ml post-operatively in a week.In the SPARC group,the Qmax changed from 31.7 ±9.4 ml/s pre-operatively to 26.9 ± 8.9 ml/s post-operatively in a week.PVR changed from 1.4 ± 3.7 ml pre-operatively to 3.5 ± 6.3 ml postoperatively in a week.All the changes were significant ( P ＜ 0.05 ).And in the SPARC group,the Qmax changed from 31.2 ± 10.0 ml/s pre-operatively to 26.2 ± 9.1 ml/s post-operatively; the PVR changed from 1.8 ± 3.2 ml pre-operatively to 4.7 ± 8.8 ml post-operatively (P ＜ 0.05). Conclusions Both the TOT sling and the SPARC sling have high cure rates for SUI.But the retropubic sling may lead to BOO and other complications,so the transobturate sling is a better treatment option for SUI.