OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

Objective To investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P＞0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)％ versus(0.54±0.27)％,total dip-loidy rate(0.25±0.27)％ versus(0.05±0.05)％,and disomy rate of chromosome 18(0.77±1.15)％ versus(0.18±0.21)％,sex chromosomes(2.79±2.38)％ versus(0.78±0.52)％,chromosome 13(0.79±0.99)％ versus(0.21±0.22)％,and chromosome 21(1.24±1.68)％ versus(0.22±0.19)％ were significantly higher than those in the control group(P＜0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18％,35.29％,41.18％,55.88％,and 47.06％,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.

Anterior cruciate ligament (ACL) injury of the knee is a common sports injury that leads to knee instability, articular cartilage degeneration, periarticular ligaments and meniscus injuries. Arthroscopic anterior cruciate ligament reconstruction (ACLR) is the gold standard in the treatment of ACL injuries, but femoral fixation, being one of the main factors affecting postoperative function after ACLR, remains controversial with various methods and no universal standard. Interference screws as a commonly used fixation method are made of various materials, among which metal screws provide strong fixation but have the disadvantages of graft damage, interference with the MRI examination, and a removal surgery. Degradable metal has good mechanical properties but its degradation is unpredictable. Bioabsorbable interference screws do not require a second operation and do not interfere with the MRI examination, but there are risks of screw breakage, dislocation, and bone tunnel widening. Sheathed interference screws increase the tendon-bone contact area but require a high level of integrity of the bone tunnel. Suspension fixation, the most commonly used method for ACLR femoral side, provides high initial strength, but may cause tendon lengthening, wiper effect and bungee effect. Cross-pin fixation such as Rigidfix, fixes the graft with two absorbable transverse nails with even stress distribution. However, it has a limited choice of femoral tunnel location,poses a risk of cross-pin fracture, and is not suitable for patients with tendons smaller than 7 mm in diameter. Over-the-top fixation does not need the building of a femoral tunnel and is more commonly used in skeletally immature, partial ACL injuries and ACLR revision surgery, where damage to the epiphysis can be avoided and can be used as a means of reinforcement. However, it is not sufficient in patients with high requirements for knee flexion stability and requires longer tendon graft.

Objective:To explore the occurrence,co-occurrence,and different subtypes of self-harm and sui-cidal behaviors among male prisoners to inform the development of targeted intervention strategies.Methods:A phenomenology in qualitative research was adopted,and 30 male prisoners with a history of self-harm behaviors,suicidal ideation and suicideattempts,were selected for semi-structured interviews.Data was analyzed by Colaizzi's seven-step method to distill themes.Results:Theme analysis revealed 4 themes and 9 sub-themes(subtypes)of the self-harm and suicidal behaviors of male prisoners,namely the initial occurrence of self-harm behaviors,non-suicid-al self-injury(NSSI)including 6 subtypes(emotional management disorder,self-punishing,antagonistic dissocia-tion,sensation seeking,self-harm without self-awareness,and instrumental self-harm),the co-occurrence of self-harm-suicide behaviors with a subtype of rational suicide,the acute suicide behavior including two subtypes(impul-sive suicide and psychiatric suicide).Conclusion:Negative emotions and emotional dysregulation are important re-lated factorsof self-harm among male prisoners.Suicidal behaviors commonly co-occurred with NSSI,and under-standing the NSSI of prisoners could provide reference for suicide prevention in prisons.There is variability in the motivation of different subtypes of NSSI in maleprisoners,and subtype-based personalized interventions could be a-dopted to reduce the occurrence of self-harm and suicidal behaviors.

OBJECTIVE: To determine the impact of the lower limb weight bearing line ratio (WBLR) on motor function recovery after high tibial osteotomy (HTO). METHODS: A retrospective analysis was conducted on 55 patients with unilateral compartment knee osteoarthritis who underwent open-wedge HTO between August 2020 and October 2023 and met the selection criteria. Based on the postoperative Lysholm score, patients were divided into two groups: the good knee function group (Lysholm score≥90, group A) and the poor knee function group (Lysholm score<90, group B). Lysholm score, American Knee Society (AKS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and visual analogue scale (VAS) score for pain were compared between the two groups. Univariate analysis was performed on baseline data including gender, age, body mass index (BMI), affected side, disease duration, Kellgren-Lawrence grade, and radiographic parameters [preoperative and postoperative medial proximal tibial angle, lateral distal femoral angle, femoral-tibial angle, hip-knee-ankle angle (HKA), WBLR, posterior tibial slope angle, and joint line convergence angle] to identify factors influencing functional recovery. Multivariate logistic regression analysis was further used to identify independent factors. Additionally, receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cut-off value of postoperative WBLR for predicting motor function recovery, and the area under curve (AUC) was calculated to assess diagnostic performance. RESULTS: All 55 patients were followed up 10-14 months (mean, 11.8 months). According to the postoperative Lysholm score, there were 30 patients in group A and 25 in group B. All postoperative clinical scores in group A were significantly better than those in group B ( P<0.05). Univariate analysis indicated that age, BMI, postoperative HKA, and postoperative WBLR were influencing factors for motor function recovery ( P<0.1). Further multivariate logistic regression analysis identified a postoperative WBLR≤55.5% as an independent factor influencing motor function recovery ( P<0.05). ROC curve analysis yielded an AUC of 0.788 and determined the optimal postoperative WBLR cut-off value for predicting motor function recovery to be 55.5% ( P<0.001). CONCLUSION A postoperative WBLR of 55.5% is associated with optimal motor function recovery after HTO.
Humans ; Male ; Female ; Osteotomy/methods* ; Retrospective Studies ; Tibia/surgery* ; Recovery of Function ; Middle Aged ; Osteoarthritis, Knee/physiopathology* ; Weight-Bearing ; Knee Joint/surgery* ; Lower Extremity ; Aged ; Adult ; Treatment Outcome

Objective To explore the mechanism by which T cell immunoglobulin and mucin domain-3(TIM-3)promotes the Hippo signaling pathway in the pathogenesis of preeclampsia.Methods HTR-8/Svneo cells were divided into a control group(Con),a recombinant human Tim-3 protein(Tim-3 Fc)group,a YAP1 inhibitor CA3 group and a Tim-3 Fc+CA3 group.Cell proliferation was analyzed by 5-ethynyl-2 '-deoxyuridine(EdU).Cell invasion and migration were evaluated by Transwell assay,and cell apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.Protein expression levels of TIM-3 and Hippo pathway components in HTR-8/SVneo cells were detected by Western Blot.Results Compared to the Con group,protein expression levels of TIM-3,YAP1 and TAZ were up-regulated in HTR-8/SVneo trophoblast cells of the TIM-3 Fc group(P<0.05).Compared to the TIM-3 Fc group,protein expression levels of YAP1 and TAZ were down-regulated in trophoblast cells of the TIM-3 Fc+CA3 group(P<0.05).Compared to the Con group,the rate of EdU positive cells in HTR-8/SVneo trophoblast cells in TIM-3 Fc group was increased significantly(P<0.05).Compared to the TIM-3 Fc group,the rate of EdU positive cells and the number of apoptotic cells in HTR-8/SVneo trophoblast cells of the TIM-3 Fc+CA3 group were decreased significantly(P<0.05).Compared to the Con group,the number of HTR-8/SVneo trophoblast cells in TIM-3 Fc group was increased significantly(P<0.05).Compared to the TIM-3 Fc group,the number of HTR-8/SVneo trophoblast cells in TIM-3 Fc+CA3 group was decreased significantly(P<0.05).Conclusions Tim-3 activates the Hippo pathway by interacting with YAP1 in trophoblast cells,thus promoting cell proliferation,invasion and migration.

Objective:The aim of this study is to analyse the clinical characteristics of Special clinical types of lung cancer nodules with "small tumors and big metastases" .Methods:From Jan. 2019 to Nov. 2024, patients with stage T1 solid lung cancer who were pathologically confirmed in the First Affiliated Hospital of Chongqing Medical University were prospectively collected and divided into lung cancer nodule with metastasis group (study group) and stage Ia lung cancer group (control group). The differences in clinical, imaging, pathological and molecular features between the two groups were compared, and the differences in the distribution of metastases in the study group and in patients with or without bone metastasis were analyzed.Results:A total of 827 patients with an average age of 62.65±11.01 years were included, including 425 in the study group and 402 in the control group. The proportion of males, number of smokers, nodule size and EGFR mutation rate in the study group were significantly higher than those in the control group (all P<0.05). Stage IV patients accounted for 63.76% in the study group, among which bone metastasis patients accounted for the highest proportion (51.66%), and alkaline phosphatase, calcium and phosphorus were significantly increased. Conclusions:Patients with smoking, male and solid lung cancer nodules are more likely to have "small tumor and large metastasis", and bone metastasis is the most common distant metastatic site. The increase of alkaline phosphatase, calcium and phosphorus is helpful for early identification of bone metastases.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.