OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient （DTP） pharmacies and propose measures for pre-emptive risk management， providing references for the quality risk management of cold chain medicines. METHODS Based on the requirements of national regulations， a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024， focusing on the receipt， storage， distribution， and delivery processes， using questionnaires， telephone interviews， and on-site visits. Common quality management issues in the operation of cold chain medicines were identified， and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures. RESULTS & CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey， and personnel from 30 DTP pharmacies participated in on-site and telephone interviews. Typical problems were identified in some DTP pharmacies， including insufficient personnel allocation or training， incomplete or inadequate implementation of quality system documentation， inadequate provision or management of cold chain facilities and equipment， and non-compliant storage and distribution of cold chain medicines. These issues posed certain risks to the quality management of cold chain medicines. It is recommended that DTP pharmacies strengthen personnel allocation and training， improve quality system documentation， enhance the provision and management of facilities and equipment， standardize storage and transportation operations， and strengthen supervision and assessment as pre-emptive measures. In addition， all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation， in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective:To explore the genetic basis for a patient with Disorders of sex development (DSD).Methods:A female patient who had presented at the Linyi People′s Hospital due to primary amenorrhea on April 6, 2022 was selected as the study subject. Conventional chromosomal karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), fluorescence quantitative PCR and Sanger sequencing were carried out for the patient. Results:The patient, a 14-year-old female, had featured short statue, multiple nevi, and primary amenorrhea. She was found to have a karyotype of 46, X, idic(Y)(p11.3)[59]/45, X[39]/47, X, idic(Y)(p11.3)×2[2]. The result of FISH assay was 46, X, der(Y).ish idic(Y)(p11.3)( SRY+ )[59]/45, X[39]/47, X, der(Y)×2.ish idic(Y)(p11.3)( SRY+ )[2]. That of CMA was arr[GRCh37](X)×1, (Y)×0-1, arr[GRCh37]Yp11.32(118552_472090)×1. The patient had no deletion in the AZF region of Y chromosome, and was negative for variant of SRY gene. Combining the above results, her molecular karyotype was determined as mos 46, X, idic(Y)(p11.32)[59]/45, X[39]/47, X, idic(Y)(p11.32)×2[2].ish 46, X, idic(Y)(p11.32)( DXZ1+, DYZ1+ +, DYZ3+ +, SRY+ )[59]/45, X( DXZ1+, DYZ1-, DYZ3-, SRY-)[39]/47, X, der(Y)×2.ish idic(Y)(p11.32)( DXZ1+, DYZ1+ +, DYZ3+ +, SRY+ )[2].arr[GRCh37](X)×1, (Y)×0-1, arr[GRCh37]Yp11.32(118552_472090)×1. The patient was diagnosed with mosaicism DSD with idic(Y)(p11.32). Conclusion:The abnormal mosaicism karyotype probably underlay the DSD in this patient.

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Objective To explore the impact of SARS-CoV-2-positive donors on the prognosis of heart transplant recipients. Methods The Medline, EMbase, CENTRAL, CNKI, Wanfang Data, VIP and China Biology Medicine from inception to May 2023 were searched by computer for studies about impact of SARS-CoV-2-positive donors on the prognosis of heart transplant recipients. The data were extracted from all the relevant literatures, and the quality of the data was assessed using the Newcastle-Ottawa Scale (NOS). All statistical analyses were conducted by the Stata 11.0 software. Results A total of 10 studies (NOS score ranging from 5 to 9 points) involving 643 patients were enrolled. The pooled results demonstrated that the pooled mortality of heart transplant recipients from SARS-CoV-2-positive donors was 4% (95%CI 2% to 5%). And the incidence of composite outcome, regarding graft failure, rejection and death as poor prognosis, was 7% (95%CI 5% to 9%). Besides, compared with recipients from SARS-CoV-2-negative donors, the pooled odds ratio (OR) value of death of SARS-CoV-2-positive donors was 0.68 (95%CI 0.38 to 1.22, Z=1.28, P=0.200). The pooled OR value of rejection rate was 0.41 (95%CI 0.27 to 0.64, Z=3.97, P<0.005). For the composite outcome, the pooled OR value was 0.50 (95%CI 0.37 to 0.69, Z=4.30, P<0.005). In addition, there was no statistical difference in the length of hospital stay between heart transplant recipients from SARS-CoV-2-positive donors and negative donors (SMD=–0.03, 95%CI –0.22 to 0.15, Z=0.36, P=0.720). Conclusion The application of heart from SARS-CoV-2-positive donor for transplantation is safe and feasible. However, further prospective studies with longer follow-up are still needed to verify its impact on long-term outcomes.

Objective To explore the application value of ultrasound-guided use of bupivacaine for subarachnoid block in hip replacement surgery for elderly femoral neck fractures.Methods A total of 108 elderly patients who underwent hip replacement surgery at Ganzhou Traditional Chinese Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into conventional anesthesia group and ultrasound guided anesthesia group by means of random number table,54 cases in each group.Patients in the conventional anesthesia group received routine general anesthesia;Patients in the ultrasound guided anesthesia group received unilateral lumbar anesthesia with bupivacaine under ultrasound-guided guidance.Compare the effectiveness of two anesthesia methods during surgery.Results Compared with the conventional anesthesia group,the anesthesia effect of the ultrasound guided anesthesia group was better(P<0.05);The surgery time,amount of bleeding during surgery,postoperative recovery time,and length of hospital stay in the ultrasound guided anesthesia group were all lower than those in the conventional anesthesia group(P<0.05).The ultrasound guided anesthesia group performed better in terms of hemodynamic stability,with a smaller range of changes,and significantly lower pain scores at different postoperative time points compared to the conventional anesthesia group(P<0.05).Conclusion In elderly patients undergoing hip replacement surgery,using ultrasound-guided bupivacaine for subarachnoid block can achieve ideal anesthesia and analgesic effects compared to traditional general anesthesia,shorten drug onset time,alleviate pain in elderly patients,maintain hemodynamic stability,and have significant clinical application effects.

Objective:To investigate the clinical and genetic characteristics of a child with microcephaly-capillary malformation syndrome due to a STAMBP mutation. Methods:The clinical data of a case of microcephaly-capillary malformation syndrome caused by STAMBP gene mutation admitted to Anhui Children′s Hospital in August 2023 were collected. The genes of the child and his parents were detected by whole exome sequencing, and the risk was predicted by biological software. At the same time, the clinical characteristics of the child were analyzed and the literature was reviewed. Results:The patient is a male child aged 2 years and 7 months. The patient had special features, microcephaly, refractory epilepsy, severe comprehensive developmental delay, and capillary malformations. The results of genetic testing showed that the STAMBP gene in the child had complex heterozygous mutations NM_001353967: c.367delG[p.E123fs *27(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp)], inherited from his mother and father respectively. The mutations have not been recorded in the HGMD, dbSNP and gnomAD databases,etc. The protein structure of the STAMBP gene was modeled that predicted c.367del(p.Glu123Lysfs *27) and c.159A>C (p.Glu53Asp) had a negative effect on the function of STAMBP protein. Conclusion:The STAMBP gene complex heterozygous mutations c.367delG(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp) may be the pathogenic factor of this child, which further expands the variation spectrum of the STAMBP gene and the genotype of microcephaly-capillary malformation syndrome, and provides guidance for family genetic counseling.

Humans ; Hypertension, Pulmonary/surgery* ; Learning Curve ; Angioplasty, Balloon ; Pulmonary Embolism/therapy* ; Chronic Disease ; Pulmonary Artery/surgery*

BACKGROUND: The biological and molecular characteristics of spread through air spaces (STAS), a newly recognized invasive mode of lung cancer, remain controversial. The aim of this study was to investigate the clinicopathological features and molecular characteristics of STAS in patients with pulmonary adenocarcinoma. METHODS: A total of 694 resected invasive non-mucinous lung adenocarcinomas diagnosed by clinicopathology from July 2019 to March 2021 in the First Affiliated Hospital of Guangzhou Medical University were collected, and the relationship between STAS and clinicopathological factors was analyzed. The state of protein expression of anaplastic lymphoma kinase (ALK) was detected by immunohistochemical method. Epidermal growth factor receptor (EGFR) was detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). ROS proto-oncogene 1-receptor (ROS1) was detected by reverse transcription-PCR (RT-PCR). RESULTS: A total of 344 STAS positive cases and 350 STAS negative cases were collected. By univariate analysis, STAS positivity was statistically associated with tumor maximum diameter (P<0.001), pleural invasion (P<0.001), lymphovascular invasion (P<0.001), nerve invasion (P=0.013), lymph node metastasis (P<0.001), clinical stage (P<0.001) and histological type (P<0.001). There was a statistical correlation between STAS and ALK protein expression (P=0.001). Multivariate analysis showed that STAS positive was correlated with pleural invasion (P=0.001), vascular invasion (P<0.001), lymph node metastasis (P=0.005)and ALK protein expression (P=0.032). CONCLUSIONS STAS is associated with highly aggressive biological behavior of lung adenocarcinoma, suggesting a poor prognosis.
Humans ; Lung Neoplasms/pathology* ; Lymphatic Metastasis ; Protein-Tyrosine Kinases ; Prognosis ; Neoplasm Staging ; Neoplasm Recurrence, Local/pathology* ; Proto-Oncogene Proteins ; Adenocarcinoma of Lung/pathology* ; Neoplasm Invasiveness ; Retrospective Studies

Background: There is no standard cut-off value of serum IgG4 concentration and serum IgG4/total IgG ratio for the diagnosis of IgG4-related disease (IgG4-RD) or as a marker of treatment responses. We aimed to explore this issue through a retrospective cohort analysis of adults in southwest China. Methods: The diagnostic performance of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD was evaluated in a retrospective analysis of 177 adults newly diagnosed as having IgG4-RD and 877 adults without IgG4-RD. Dynamic analysis was performed to evaluate the significance of serum IgG4 concentration on IgG4-RD treatment responses. Results: The serum IgG4 concentration differed according to sex. The optimal cut-off values of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD diagnosis were 1.92 g/L and 0.12 in males and 1.83 g/L and 0.11 in females, respectively. For patients with serum IgG4 concentration >2.01 g/L, the cut-off values in the total population were >3.00 g/L and 0.19, respectively. The median serum IgG4 concentration decreased over time, and the decrease rate increased over time. The serum IgG4 concentration significantly decreased at >1 week post-treatment (P=0.004), and the median decrease rate was close to 50% at >4 weeks post-treatment. Conclusions Serum IgG4 can be a good indicator for IgG4-RD diagnosis; however, different diagnostic cut-off values should be determined according to sex. The decreasing rate is more conducive than the serum IgG4 concentration to monitor treatment efficacy. The IgG4/IgG ratio did not improve the diagnostic efficacy for IgG4-RD.