ObjectiveTo investigate the variation of drug resistance genes in human immunodeficiency virus (HIV)-1 strains in Huzhou City, Zhejiang Province, so as to provide a basis for guiding the adjustment of treatment plans for ADIS patients or patients infected with HIV. MethodsA total of 555 samples were collected from 396 newly diagnosed HIV/AIDS patients who did not receive antiviral treatment from 2021 to 2023, in addition to 159 HIV/AIDS patients who received antiviral treatment for at least twelve months but failed during the same period.Reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nested PCR) were used to amplify the pol region gene of HIV-1. Lastly, the sequenced data were submitted to the HIV resistance database of Stanford University in the United States for resistance gene mutation analysis. ResultsDrug resistance mutations were detected in samples from 97 newly diagnosed HIV/AIDS patients and 77 patients with failed treatment, with the main subtypes being CRF01AE and CRF07-BC. The mutation rates of drug resistance genes in the patients untreated and patients with failed treatment were 24.49% (97/396) and 48.43% (77/159), respectively. Drug resistance gene mutations against protease inhibitor (PI), nucleotide reverse transcriptase inhibitor (NRTI), and non-nucleoside reverse transcriptase inhibitor (NNRTI) were detected both in the untreated and failed treatment group. The drug resistance rates of untreated and failed treatment patients were 10.61% (42/396) and 45.28% (72/159), respectively. ConclusionThe pre-treatment drug resistance rate of HIV-1 strains in Huzhou City is at a moderate level, and which is at a relatively low level nationwide after antiviral treatment. The resistance genes in the region exhibit diverse and complex characteristics, and the prevalence of drug resistance is in the process of upward and evolution compared to the monitoring results in the previous years. It is necessary to continue to monitor the occurrence and development of drug resistant strains, and to adjust treatment plans in time to prevent the occurrence of transmissible drug resistance.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

Objectives:To report a novel mutation site in the pathogenic gene TTR of transthyretin cardiac amyloidosis(ATTR-CA),and to identify family members at risk,and provide suitable clinical diagnosis and treatment. Methods:A retrospective analysis was conducted on the clinical data of the proband with ATTR-CA who visited the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University in March 2021.The proband underwent whole exome sequencing using high-throughput methods to detect mutation genes.Sanger sequencing was used to test candidate pathogenic loci in suspected family members,and relevant literature was reviewed. Results:Among 51 individuals spanning 5 generations in the pedigree,10 family members(including the proband)carried the heterozygous TTR gene c.163A>G mutation,resulting in the amino acid residue at position 55 changing from lysine(Lys)to glutamic acid(Glu).This mutation follows an autosomal dominant inheritance pattern,with early onset in adulthood,rapid progression,and presenting as a mixed-type ATTR-CA.Five mutation carriers had different clinical manifestations,while the remaining 5 mutation carriers,who are at younger age,have not yet shown symptoms.Within the pedigree,7 individuals died(the proband's uncle[Ⅱ-1]who died from stroke at 65 years old,the rest 6 family members died from heart disease before the age of 50). Conclusions:According to the American College of Medical Genetics and Genomics guidelines,TTR gene Lys55Glu mutation is classified as likely pathogenic,this mutation site has not been reported in the literature before.Present study adds clinical evidence that might broaden the spectrum of TTR mutations.

Objective To analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.

Objective:To evaluate the impact of bladder volume on dosimetric parameters of clinical target volume (CTV) and organs at risk (OAR) of intensity modulated proton therapy (IMPT) for localized prostate cancer during the treatment planning and daily treatment.Methods:Clinical data of 25 patients with localized prostate cancer admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to June 2022 and enrolled in the "Proton Therapy System" (SAPT-PS-01) registered clinical trial were retrospectively analyzed. All patients were male and the median age was 72 years old. A total of 30 sets of IMPT plans were obtained. Based on the planning CT (30 sets) and weekly verification CT during treatment (172 sets), bladder volume, CTV and OAR dose parameters were collected. Spearman correlation analysis was used to evaluate the correlation between bladder volume in CT and the dosimetric parameters of CTV and OAR during IMPT plans, and Wilcoxon-Mann-Whitney test was adopted to compare the dosimetric parameters of CTV and OAR among different bladder volume change groups.Results:The V 95% of CTV1 and CTV2 were both 100.0%±0.0% in IMPT plans. Bladder volume was significantly negatively correlated with D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE) of the bladder ( P<0.001, 0.003, <0.001, <0.001,<0.001), and D mean, V 50 Gy(RBE) of the small intestine (both P<0.001). During treatment, bladder D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE)( P<0.001, 0.001, <0.001, <0.001, <0.001), rectal D mean, V 50 Gy(RBE), V 40 Gy(RBE) (all P<0.001), small intestine D mean, V 50 Gy (RBE) (both P<0.001) of patients with bladder volume increase >20% compared to baseline were significantly decreased compared to those in IMPT plans. But CTV1 V 100%, and CTV2 V 95% were significantly decreased too( P=0.029, 0.020). In the bladder volume decreased>20% patients, the D mean, V 70 Gy(RBE), V 60 Gy(RBE), V 50 Gy(RBE), V 40 Gy(RBE) of the bladder were significantly increased compared to those in IMPT plans (all P<0.001). However, a bladder volume reduction of ≤20% and increase of ≤20% from baseline had no significant impact on CTV and OAR dosimetric parameters during treatment. Conclusions:For patients with localized prostate cancer undergoing proton therapy, a certain bladder volume should be ensured during planning CT scans. During the daily treatment, the bladder volume should be maintained between 80%-120% of the baseline level to ensure CTV coverage and good dose sparing to OAR.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

OBJECTIVE To explore the effect of changing lifestyle diet in the treatment of laryngeal reflux disease(LRPD).METHODS A total of 92 patients with LRPD who received outpatient treatment in the Second Affiliated Hospital of Fujian Medical University from January 2022 to June 2023 were selected as the study control,divided into control group(46 cases)and treatment group(46 cases).The control group was treated with conventional acid suppression and gastric motogenic therapy.The treatment group was treated on the basis of the control group with giving guidance on lifestyle and diet.The changes of reflux symptom index scale(RSI)and reflux sign score scale(RFS)and the clinical efficacy of the two groups were compared 8 weeks and 12 weeks after treatment.RESULTS RSI total score was improved 8 weeks after treatment compared with before treatment in both RSI control group and treatment group(P＜0.05).The total RSI score of 12 weeks after treatment was improved compared with that of 8 weeks after treatment in both control and treatment groups(P＜0.05).The total RFS score at 8 weeks after treatment was improved in both control group and treatment group compared with before treatment(P＜0.05).Compared with 8 weeks after treatment,the total RFS score in both control group and treatment group was improved(P＜0.05).After 8 weeks of treatment,the total effective rate of the control group(60.9%)was compared with that of the treatment group(71.7%),and there was no significant difference between the two groups(χ2=1.335,P=0.513).After 12 weeks of treatment,the total effective rate of the control group(73.9%)was compared with the total effective rate of the treatment group(91.3%),and the difference between the two groups was statistically significant(χ2=6.226,P=0.044).CONCLUSION The change of lifestyle and diet should become an important part of the treatment of LRPD.By adjusting the unhealthy lifestyle and diet,the symptoms of patients can be significantly reduced and better clinical efficacy can be obtained.

Objective To discuss the application of therapeutic hemapheresis in clinical therapy and to observe the ad-verse reactions.Methods 126 times of therapeutic hemapheresis were performed in 121 patients by Nangel blood cell sepa-rator.Consumables and apheresis procedures were selected according to different treatment needs of patients.The clinical therapeutic efficacy laboratory indicators and adverse reactions during the treatment process were analyzed,and correspond-ing measures were taken.Results Among 100 patients who underwent platelet rich plasma(PRP)treatment,the success rate of collection was 98％.The average PRP platelet level achieved(981.22±3.55)×109/L,and the average concentration multiple of PRP achieved(4.01±0.52)times.All patients obtain symptomatic relief after treatment with PRP.The level of hemoglobin and red blood cell count of 6 polycythemia vera patients and the level of platelet of 10 essential thrombocythemia patients all decreased after therapeutic hemapheresis combined with hydroxycarbamide,with significant difference(P＜0.05).Five patients with preoperative autologous blood donation have been through the surgery successfully.Out of the 121 patients,10(8.26％)experienced mild adverse reaction(8.26％),15(12.40％)showed bruising and bleeding at puncture site,and 1(0.83％)had pseudoaneurysm.Conclusion Therapeutic hemapheresis has the advantages of good curative effect,high success rate and low incidence of adverse reactions,and can be applied in PRP collection,removal of blood pathological components and preoperative autologous blood donation.

Objective To compare the analgesic effect, duration and incidence of adverse reactions of liposome bupivacaine (LB) and bupivacaine hydrochloride after intercostal nerve block in single-port thoracoscopic lung surgery. Methods In Department of Thoracic Surgery of the First Affiliated Hospital of Xinxiang Medical University between September 2023 and March 2024, 228 patients who needed to undergo thoracoscopic lung surgery were selected and divided into two groups by random number table method: a group B with bupivacaine hydrochloride (n=118), and a group LB with LB (n=110). Intraoperative intercostal nerve block was performed under endoscopy, and the time of first use of analgesic drugs after surgery, cumulative use of opioids 72 h after surgery, incidence of postoperative nausea and vomiting, length of stay and other indicators were evaluated and recorded. Results Visual analogue scale (VAS) scores at 4 h, 8 h, 12 h, 24 h, 48 h and 72 h in the LB group were significantly lower than those in the group B (P<0.05). The total number of activities within 48 h after surgery in the group B was significantly lower than that in the LB group (P<0.05), and the postoperative hospitalization stay in the LB group was shorter than that in the group B, but the difference was not statistically significant. There was no statistical difference between the two groups in postoperative adverse reactions. Conclusion Intercostal nerve block with LB during single-port thoracoscopic lung surgery can significantly reduce postoperative pain, improve quality of life, and promote recovery of the patients. It is worthy of clinical application.