[Analysis of problems and management of in vitro diagnostic reagent clinical trials in medical laboratory].

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory's experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

[Progress in surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava].

Hepatocellular carcinoma(HCC) is one of the most common malignancies of the digestive system,which is prone to be associated with microvascular or macrovascular invasion. Among them,HCC with inferior vena cava tumor thrombus(IVCTT) or right atrium tumor thrombus(RATT) is rare and has a poor prognosis. However,surgical treatment of HCC with IVCTT and (or) RATT is rarely reported and summarized. The review described the classification of HCC tumor thrombus with IVCTT and (or) RATT, summarized the progress of surgical approaches and surgical operations,and introduced a case of thrombectomy after pushing from the outer surface of the atrium,rendering the RATT to the inferior vena cava under non-cardiopulmonary bypass. The review also proposed the prospective treatments for HCC with IVCTT or RATT,providing clinical guidance to hepatobiliary surgeons.

[Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis patients with fibromyalgia].

OBJECTIVE: To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting. METHODS: Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group. RESULTS: There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups. CONCLUSION: The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

Direct Measurement of the Astrophysical

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

[Effect of functional exercises on patients with rheumatoid arthritis: a meta-analysis].

OBJECTIVE: To evaluate the effect of functional exercises on disease activity, joint function and quality of life of patients with rheumatoid arthritis (RA). METHODS: Randomized controlled trials were searched in Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), VIP database and Wanfang database with keywords being "rheumatoid arthritis/RA", "function exercise (training)/joint exercise (training)/physical exercise (training)/resistance movement (exercise)/isotonic and isometric/stretching exercise/muscle exercise", and "trials/clinical trials". Then literature selection, extraction and literature quality evaluation were carried out by two of the authors independently following the including and excluding standards. Then the outcome indicators were analyzed with Review Manager 5.3 software. RESULTS: In the study, 2 173 articles were achieved by searching in databases, including 1 522 English papers and 651 Chinese papers. Then 913 duplicated papers were identified and removed using EndNote software. After reading the titles and abstracts, 1 194 papers were excluded that did not satisfy the including standards. Finally, the full texts of these papers were read and papers with insufficient data were excluded, resulting in 13 included papers for systematic review, including 8 English and 5 Chinese papers. A total of 812 cases were studied in these papers, including 426 in the experimental groups and 386 in the conventional groups. For the outcome index in these articles, disease activity score 28 (DAS28) was used in 5 of them, health assessment questionnaire (HAQ) was used in 8 articles, visual analogue scale (VAS) for pain was used in 6 articles, and morning stiffness duration was used in 3 articles. The meta-analysis showed that functional exercises could delay the development of the disease activity of RA patients (mean difference=-0.76; 95%CI: -1.13, -0.38; P<0.001), improve the joint function (mean difference=-0.36; 95%CI: -0.47, -0.24; P<0.001), alleviate the pain of joints (mean difference=-1.75; 95%CI: -1.98, -1.53; P<0.001), and reduce the duration of morning stiffness (mean difference=-17.65; 95%CI: -22.09, -13.21; P<0.001). CONCLUSION: This study showed the positive effects of functional exercises on alleviating the pain of joints, reducing the morning stiffness duration, and delaying the disease exacerbation of RA patients. It has a positive effect on improving the joint function and improving the quality of life in patients with RA.

[Clinical analysis of the risk factors for No.12p LN metastasis in advanced gastric cancer].

Objective: To analyse the risk factors for periportal lymphnode (No.12p LN) in advanced gastric cancer. Methods: A retrospective analysis of 183 patients with advanced gastric cancer from January 2005 to December 2010, and all patients were underwent D2 lymphadenectomy in addition to No. 12p LN dissections. Potential clinicopathological factors that could influence No. 12p LN metastasis were statistically analyzed. Results: There were 18 cases (9.8%) with periportal lymphnode metastasis. A logistic regression analysis suggested that the Borrmann type (Ⅲ/Ⅳ versus Ⅰ/Ⅱ, P=0.008), tumor size (≥6 cm vs <6 cm, P=0.001), and depth of invasion (pT4 vs pT2/pT3, P=0.049) were associated with 9.5-, 8.5-, and 3.2-fold increases, respectively, for risk of No. 12p LN metastasis. A logistic regression analysis also showed that No. 5 (P=0.002) and No. 12a (P=0.002) LN metastasis were associated with 7.5- and 7.3-fold increases, respectively, for risk of No. 12p LN metastasis. In addition, significant differences in 5-year survival of patients with and without No. 12p LN metastasis were observed (11.1% vs 32.7%, P=0.042). Conclusions: Borrmann type, tumor size and depth of invasion are significant factors for identifying patients with No. 12p LN metastasis. Patients with No. 5 or No. 12a LN metastasis should be higher possibility of No.12p LN metastasis.

Detection of gastrointestinal pathogens in oncology patients by highly multiplexed molecular panels.

We compared the frequency of gastrointestinal (GI) pathogen detection in an oncology patient population by two multiplexed molecular assays, the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP, which identifies 14 GI pathogens) and the BioFire Gastrointestinal Panel (BFGP, which identifies 22 GI pathogens). We additionally reviewed the clinical characteristics of patients tested with both panels. A total of 200 prospectively collected and 81 archived stool samples were tested by both panels. In the prospective cohort, the GPP and BFGP identified a pathogen in 33.5% [95% confidence interval (CI): 27.3-40.35%] and 39.6% (95% CI: 33.0%-46.6%) of samples, respectively (p = 0.25). The BFGP detected significantly more pathogens than the GPP (p = 0.038), with 21.3% of samples positive for targets only detected by the BFGP. The concordance between the assays was very good at 91.1% (κ = 0.8, 95% CI: 0.7-0.9) when considering only pathogens detected by both assays. The most frequent pathogens detected were Clostridium difficile, norovirus, Campylobacter, and Salmonella species. On the archived samples, the BFGP was positive in 92.6% of samples but detected more pathogens than the GPP (86 vs. 97, p = 0.033), including both targets unique to the BFGP and targets common to both panels. A pathogen was more frequently detected in patients with hematological malignancies than solid tumors and in ambulatory patients compared to hospitalized patients, but these differences were not statistically significant. Overall, the detection rates were similar for both the GPP and the BFGP, and the latter detected more than one pathogen in additional patients. The impact of increased detection of GI pathogens by multiplexed panels on the clinical care of oncology patients will require further investigation.

[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma].

Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. Results: The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, P<0.05 for HER2; and 4 months vs 10 months, P<0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2; and 13 months vs 43 months, P<0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion: HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

[Value of single-source dual-energy CT (ssDECT) in differentiating lipid-poor adrenal adenomas from metastatic lesions].

Objective: To evaluate the value of single-source dual-energy CT (ssDECT) in differentiating lipid-poor adenomas from metastases in adrenal glands. Methods: From August 2011 to Oct 2014, 63 patients with 73 adrenal nodules (53 metastases proven by 5-6 months follow-up, and 20 histopathologically proven adenomas, CT value > 10 HU) underwent ssDECT scanning. The CT values of conventional polychromatic CT and virtual monochromatic images (40-140 keV) , fat-water density images and effective atomic number (eff-Z) were reconstructed on an ADW4.5 workstation and ROC curves were then constructed to evaluate the effectiveness of each parameter. The slope of spectral curve was measured and divided into 3 types: increment curve (K>0.1), straight curve (-0.1≤K≤0.1) and decrement curve (K< -0.1) according to the slope (the value of K) of spectral curve, and the curve patterns in the two groups were compared statistically. Results: There was no statistical difference between the mean CT values of metastases (35.12±5.29)HU and lipid-poor adenomas (32.48±6.94)HU by conventional polychromatic CT (P>0.05). The range of single-energy CT values of metastases [from (53.00±15.12) HU to (33.38±5.67) HU] was significantly higher than that of lipid-poor adenomas [from (26.90±26.94) HU to (28.77±10.66) HU] at energy levels ranging from 40 to 80 keV (P<0.05). There was no significant difference between the single-energy CT value of metastases and lipid-poor adenomas at energy levels ranging from 90 to 140 keV (P>0.05). The median fat-water concentration of metastases was -164.61 µg/cm3, significantly lower than that of lipid-poor adenomas (114.32 µg/cm3,P<0.05). The eff-Z of metastases (7.76±0.15) was also significantly higher than that of lipid-poor adenomas (7.50±0.25, P<0.05). When the threshold of fat-water concentration was -143.89 µg/cm3, the sensitivity, specificity and accuracy rate of metastasis diagnosis was 70.0%, 66.0%, and 76.7%, respectively. When the threshold of eff-Z was 7.63, the sensitivity, specificity and accuracy rate of metastasis diagnosis was 83.0%, 65.0%, and 80.4%, respectively. The lower the energy, the higher the diagnostic accuracy at energy levels ranging from 40 to 80 keV, and that of 40 keV was the highest. The spectral curves of metastases included 2 (3.8%) ascending curves, 9 (17.0%) straight curves and 42 (79.2%) descending curves, while in the 20 lipid-poor adenomas, there were 9 (45.0%) ascending curves, 4 (20.0%) straight curves and 7 (35.0%) descending curves, showing significant differences between the two groups (P<0.05). Conclusions: Single-source dual-energy CT provides an effective multi-parameter approach for differentiating lipid-poor adrenal adenomas from metastases.

[Microsurgical management of petroclival meningiomas combined trans-subtemporal and suboccipital retrosigmoid keyhole approach].

OBJECTIVE: With the development of modern skull base minimally invasive technology mature and neural radio surgery techniques, it is necessary to re-examine the therapeutic strategy for the treatment of petroclival meningiomas. To sum up the operative experience and methods in microsurgical resection of petroclival meningiomas by the combining trans-subtemporal and suboccipital retrosigmoid keyhole approach. To explore the minimally invasive operation approach of petroclival meningiomas, to raise the removal degree and to improve the postoperative result using this approach. METHODS: The clinical data of the consecutive 21 patients with the petroclival meningiomas were reviewed retrospectively. The method, degree of tumor resection,techniques of the combining keyhole approach, Karnofsky performance score (KPS) before and after operation were also analyzed. The neuronavigation guided operation was performed in 9 cases, and 12 cases were operated in the neuroelectrophysiological monitoring. RESULTS: Total excision of the tumor resection (Simpson, I-II levels) was conducted in 18 cases (85.7%, 18/21), and 3 patients underwent close resection (Simpson III level, 14.3%, 3/21). Postoperative three-dimensional CT showed good lock bone flap restoration; Postoperative pathology confirmed meningioma. Postoperative cranial nerve dysfunction or new original nerve dysfunction were aggravated in 5 cases (23.8%) , including transient trochlear nerve (3 cases), abducent nerve (1 case), and the motor branch of trigeminal nerve paralysis (1 case). Abducent nerve paralysis (1 case) appeared, with hearing impairment. After the 3-month follow-up, 11 cases had the same KPS aspreoperation, 7 cases improved, and 3 cases not improved. The KPS score was 77.14±23.12 on average, and there was no statistically significant difference compared with that before operation (P>0.05). The postoperative follow-up for half a year showed fluent speaking and writing in 19 cases (KPS 70 or higher), and general recovery in 2 cases (KPS<70). The postoperative follow-up for 3-29 months showed no tumor recurrence or progress. CONCLUSION: The combining trans-subtemporal and suboccipital retrosigmoid keyhole approach is simple, safe, and minimally invasive, and an ideal operation approach of petroclival meningioma. To master the operation skills and the intraoperative matters needing attention in the operation, is favorable to improve the resection rate and curative effect.

[Microsurgical management of petroclival meningiomas combined trans-subtemporal and suboccipital retrosigmoid keyhole approach].

OBJECTIVE: With the development of modern skull base minimally invasive technology mature and neural radio surgery techniques, it is necessary to re-examine the therapeutic strategy for the treatment of petroclival meningiomas. To sum up the operative experience and methods in microsurgical resection of petroclival meningiomas by the combining trans-subtemporal and suboccipital retrosigmoid keyhole approach. To explore the minimally invasive operation approach of petroclival meningiomas, to raise the removal degree and to improve the postoperative result using this approach. METHODS: The clinical data of the consecutive 21 patients with the petroclival meningiomas were reviewed retrospectively. The method, degree of tumor resection,techniques of the combining keyhole approach, Karnofsky performance score (KPS) before and after operation were also analyzed. The neuronavigation guided operation was performed in 9 cases, and 12 cases were operated in the neuroelectrophysiological monitoring. RESULTS: Total excision of the tumor resection (Simpson, I-II levels) was conducted in 18 cases (85.7%, 18/21), and 3 patients underwent close resection (Simpson III level, 14.3%, 3/21). Postoperative three-dimensional CT showed good lock bone flap restoration; Postoperative pathology confirmed meningioma. Postoperative cranial nerve dysfunction or new original nerve dysfunction were aggravated in 5 cases (23.8%) , including transient trochlear nerve (3 cases), abducent nerve (1 case), and the motor branch of trigeminal nerve paralysis (1 case). Abducent nerve paralysis (1 case) appeared, with hearing impairment. After the 3-month follow-up, 11 cases had the same KPS aspreoperation, 7 cases improved, and 3 cases not improved. The KPS score was 77.14±23.12 on average, and there was no statistically significant difference compared with that before operation (P>0.05). The postoperative follow-up for half a year showed fluent speaking and writing in 19 cases (KPS 70 or higher), and general recovery in 2 cases (KPS<70). The postoperative follow-up for 3-29 months showed no tumor recurrence or progress. CONCLUSION: The combining trans-subtemporal and suboccipital retrosigmoid keyhole approach is simple, safe, and minimally invasive, and an ideal operation approach of petroclival meningioma. To master the operation skills and the intraoperative matters needing attention in the operation, is favorable to improve the resection rate and curative effect.

The Risk Factors of Chronic Kidney Disease among Nursing Home Residents.

BACKGROUND: The prevalence of end-stage renal disease in Taiwan is the highest in the world; haemodialysis accounts for about 7% of the expenditure of the National Health Insurance. Nursing home residents with chronic kidney disease (CKD) have not been identified yet in Taiwan, along with associated risk factors. The objective of this study is to investigate the risk factors of CKD in long-term care facilities in Taiwan and those significantly associated with the presence of CKD. METHODS: The nursing home residents who received health examination between January and June 2012, age ≥ 55 years, were enrolled in this study. They were categorized into two subgroups according to estimated glomerular filtration rate (eGFR): < 60 and ≥ 60 mL/min. Risk factors were evaluated per recommendations from the National Kidney Foundation: body mass index (BMI), waist circumference, blood pressure, fasting glucose and lipid profile. Metabolic syndrome among the residents was also identified. RESULTS: Fifty-three nursing home residents were enrolled in the final study; 16 (30%) had eGFR below 60 mL/min, and nine (56%) of them had BMI higher than 25 kg/m2. The residents with advanced CKD had significantly higher BMI, triglyceride and lower high-density lipoprotein (HDL). Twelve (75%) had metabolic syndrome. Central obesity was observed in 10 (63%) with advanced CKD. CONCLUSION: Most of the nursing home elderly with advanced CKD have poor control of associated risk factors, including obesity, hypertension, dyslipidaemia and hyperglycaemia. For them, metabolic syndrome may be a major contributant to the aetiology. Monitoring their BMI and waist circumference is a simple but effective way to suspect the presence of CKD.

Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBeAg loss.

Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue (NA) therapy and the impact of these changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and cccDNA via real-time fluorescent PCR. In situ detection of CD4(+) , CD8(+) T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV-specific IFN-γ-producing CD4(+) T cells in patients with HBeAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8(+) T lymphocytes increased in patients with HBeAg loss compared with baseline values. Only one patient without HBeAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV-DNA decline, which could promote the recovery of antiviral immunity and facilitate HBeAg loss.

Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients.

To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (C(min)) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95% CI, 0.839-0.978; P = 0.011), baseline platelet count (OR = 0.989; 95% CI, 0.977-1.000; P = 0.049), C(min) (OR = 1.545; 95% CI, 1.203-1.983; P = 0.001), and APACHE II score (OR = 1.130; 95% CI, 1.003-1.273; P = 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when C(min) ≥ 2 mg/L, the probability of bacterial eradication was more than 80%; when C(min) ≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of C(min) between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.

CT-guided radioactive ¹²5I seed implantation treatment of multiple pulmonary metastases of hepatocellular carcinoma.

AIM: To investigate the clinical value of computed tomography (CT)-guided radioactive (125)I seed implantation for the treatment of multiple pulmonary metastases of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2007 to August 2010, 27 HCC patients with pulmonary metastases who had received computed tomography (CT)-guided radioactive (125)I seed implantation were enrolled in the study. All patients had ≥ 2 metastatic lesions (mean diameter 2 ± 0.6 cm). Under CT-guidance, (125)I seeds were implanted into the pulmonary metastases using the plane implantation technique. RESULTS: Among 27 cases, complete response, partial response, stable disease, and progressive disease were observed in four, 15, six, and two cases, respectively, during 6-48 months (mean 20.1 ± 2.2 months) of follow-up CT. The response rate was 92.6%. The mean follow-up time after (125)I implantation was 20.1 months (range 6-48 months). The survival rates at 1 and 2 years were 67% and 30.8%, respectively, with a median survival of 13.5 months. Side effects during the procedure included minor pulmonary effusions and pneumothorax. Pulmonary haemorrhage was observed in 18 cases and haemoptysis occurred in five patients. Radial shadows were observed in three cases on follow-up CT images, and seed migration in two cases on follow-up spiral CT images. CONCLUSION: CT-guided radioactive (125)I seed implantation may be a safe and effective treatment option for HCC patients with multiple pulmonary metastases.

Development of a selective and differential medium for capsulated Lactococcus garvieae.

A selective and differential medium termed 'LG agar' was developed for the isolation and presumptive identification of Lactococcus garvieae that results in black colonies with red halos. In this study, all 14 strains of L. garvieae and only 9 of the 148 strains representing 38 other species were able to grow on the LG agar. The nine viable strains on LG agar plates (including Enterococcus faecalis, Enterococcus faecium, Lactococcus lactis, Vibrio fluvialis, Vibrio furnissii, Vibrio mimicus and Vibrio salmonicida) were further differentiated from L. garvieae by various colours or colony features. Colonies isolated from the mixing culture and the infected giant sea perch using LG agar plates were all positively identified as L. garvieae by conventional tests and 16S rDNA sequencing. Furthermore, LG agar discriminated capsulated strains of L. garvieae, which were believed to be correlated with pathogens of fish and shellfish, from non-capsulated ones by colony appearances. The specificity and differentiating ability of LG agar suggest that this medium displays considerable potential for primary isolation and presumptive identification of L. garvieae from pathological and environmental samples.

[A multicenter study on the effects of congenital cytomegalovirus infection on hearing loss].

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.