Volume 102 ·  Issue 40 ·  2022

Herpes zoster (HZ) is a common viral disease that mainly affects the elderly population with a rising incidence. The occurrence of postherpetic neuralgia (PHN) is the dominant and thorny complication, which thus further aggravates the disease burden. Vaccination and clinical application of small molecules and biologics for certain diseases are identified as new risk factors for the development of HZ development. HZ vaccination has emerged as a pivotal prevention measure against the occurrence of HZ. Refining the diagnosis and early standardized antiviral treatment of HZ is the key to improve standardized management strategy.

Currently, the diagnosis, treatment and management of herpes zoster-associated pain are not well understood in China. The expert consensus on the whole-process management of herpes zoster-associated pain was focused on the standardization of diagnosis and treatment of herpes zoster-associated pain, such as the time definition of clinical stages, the relevant details of analgesic drugs and minimally invasive interventional therapy, and the value of vaccines in pain management. This article gives a detailed interpretation of the associated content in the consensus.

Nucleoside/Nucleotide analogues (NAs) are widely used for the antiviral treatment of chronic hepatitis B (CHB), however, it is difficult to achieve serum hepatitis B surface antigen (HBsAg) loss with NAs therapy. In recent years, several prospective trails have reported that HBsAg loss (functional cure or clinical cure) also occurs in a small number of hepatitis B e antigen (HBeAg) negative CHB patients who discontinued long-term treatment with NAs. Accordingly, the "stop-to-cure" strategy is proposed. Although the mechanism has not been fully elucidated, the known factors related to serum HBsAg loss with NAs withdrawal include HBV genotype, duration of NAs treatment, serum HBsAg and HBV RNA levels at end-of-treatment, and ethnic differences. In the review, we discuss the best time to stop NAs therapy, the potential markers for predicting relapse after cessation of NAs and the possible mechanism of "stop-to-cure" in HBeAg-negative CHB patients, and propose some suggestions on the time of retreatment.

Neutropenia refers to neutropenia or lack of neutrophils caused by various etiologies and different pathogenesis. In severe cases, it is easy to combine with various infections, and the disease is heterogeneous. It is a common clinical problem. In order to better guide the clinical practice of domestic doctors and improve the diagnosis and treatment level of neutropenia, the Red Blood Cell Disease (Anemia) Group of Hematology Branch of Chinese Medical Association organized many discussions with relevant domestic experts, and on the basis of forming recommendations, referring to domestic and foreign progress and reviews, the diagnosis process, differential diagnosis, treatment and other related contents of neutropenia were sorted out and a consensus was formed for clinicians' reference.

Pathogenic microbial bacteria (viruses) are human infectious or even infectious microorganisms that can be cultivated, identified, classified and given fixed numbers by depository institutions, including viruses, bacteria, fungi, rickettsia, parasites, etc. As a special experimental material, it is widely used in the research and development of diagnostic reagents, vaccines, drugs, reference materials, and scientific research related to infectious disease prevention and control. It is not only directly related to the accuracy and reliability of scientific research results, but also related to the biosafety of scientific research activities. In order to implement the Biosafety Law of the People's Republic of China, further standardize the use of pathogenic microbial bacteria (viruses) in scientific research, and continuously improve the strategic guarantee and support level of pathogenic microbial bacteria (viruses) in China for biosafety scientific and technological innovation, the National Pathogenic Microbial Collection Center/National Pathogenic Microbial Resource Bank organized relevant experts in the fields of pathogenic microbial resource preservation, infectious disease prevention and control, laboratory biosafety, academic publication and other fields to compile the Expert Consensus on Standardizing the Use of Pathogenic Microbial Bacteria (Viruses) in Scientific Research. Based on the literature investigation method and expert argument method, focusing on all links and the whole process of using pathogenic microbial bacteria (viruses), 23 consensus in six aspects based on four principles of "controllable risk, legal source, reliable quality and property right protection" is put forward, which can be used by relevant institutions and practitioners for reference in scientific research activities related to pathogenic microbial bacteria (viruses).

To analyze the clinical features and risk factors of herpes zoster and the risk factors of postherpetic neuralgia (PHN).

A total of 2 840 patients diagnosed with herpes zoster in Peking University People′s Hospital from January 2021 to April 2022 were included. The patients with herpes zoster were aged (59±16), and of which 1 314 (46.3%) patients were male. The patients were divided into PHN group and non-PHN group according to whether the patients with herpes zoster developed PHN. And there were 442 (15.6%) patients developed PHN aged (68±12), and of which 189 (42.8%) were male. The information and medical history of PHN group and non-PHN group were collected. The information of the use of glucocorticoids, immunosuppressive agents, biological agents and targeted medicine within 2 months before herpes zoster occurred, history of surgery within 6 months before herpes zoster occurred, and the duration of PHN were collected. Logistic regression analysis was used to analyze the risk factors of PHN.

Out of 2 840 patients, 2 056 (72.4%) with herpes zoster aged 50 years and above. Intercostal nerves was mostly involved in patients with herpes zoster, with a total of 1 532(53.9%). Hypertension (465 cases, 16.4%) accounted for the highest number of patients with chronic diseases, followed by diabetes (337 cases, 11.9%) and coronary heart disease (283 cases, 10.0%). Rheumatoid arthritis (41 cases, 1.4%) accounted for the highest number of patients with connective tissue diseases, followed by Sjogren′s syndrome (31 cases, 1.1%), systemic lupus erythematosus (28 cases, 1.0%). Logistic regression analysis showed that age≥50 years old (OR: 4.581; 95%CI: 3.131-6.705),lesion on the upper limb and shoulder (OR: 1.858; 95%CI: 1.129-3.059), hypertension (OR: 1.963; 95%CI: 1.513-2.546) and immunosuppressive treatments (OR: 2.170; 95%CI: 1.254-3.753) were independent risk factors for PHN (all P<0.05).

Herpes zoster mostly occurs in people aged 50 and above, and mainly affected intercostal nerves. The most common complications are hypertension and rheumatoid arthritis. Age≥50, lesion on upper limbs and shoulders, hypertension, and immunosuppressive treatments may be independent risk factors of PHN.

To evaluate the efficacy and safety of lidocaine plaster combined with gabapentin in the treatment of herpes zoster neuralgia (HZN).

A total of 93 patients diagnosed with HZN from June 4, 2021 to January 5, 2022 in the Department of Pain Clinic of Nanjing Drum Tower Hospital were selected, and their gender was not limited. They were divided into 3 groups by random number table method: group A (n=32) prescribed gabapentin alone, group B (n=30) lidocaine plaster alone, and group C (n=31) lidocaine plaster combined with gabapentin. After excluding patients who did not meet the criteria, there were 28 cases in group A, 28 cases in group B, and 29 cases in group C. The visual analogue scale (VAS), the short-form McGill pain questionnaire (SF-MPQ) score, and drug dosage and adverse reaction in each group at pre-treatment (T0), post-treatment in one week (T1), in two weeks (T2), in four weeks (T4), and in 12 weeks (T12) were recorded and evaluated; Pittsburgh Sleep Quality Index (PSQI) score and Medical Outcomes Study short-form 36 (SF-36) score at T0, T4, and T12 were recorded. Adverse reactions and drug dosage in each group were documented. Repeated measures ANOVA was used to compare the curative effects of the three groups at different time points before and after treatment.

The ages of the three groups of patients were (67.8±10.0), (60.9±11.4) and (63.5±12.5) years old respectively (P=0.318), and the proportions of men were 46.4 % (13 cases), 35.7% (10 cases) and 44.8 % (13 cases), respectively (P=0.472). After treatment, the VAS scores and SF-MPQ scores of patients in the three groups were decreased at each time point compared with those before treatment (all P<0.05), the VAS and SF-MPQ scores of patients in group C at T12 time point were 1.2±0.4 and 5.2±2.4 respectively, which were lower than those of patients in groups A and B (both P<0.05). The dosages of gabapentin and lidocaine plaster in group C were lower than those in groups A and B at each time point after treatment (all P<0.05). The PSQI scores of patients in the three groups at T4 and T12 were lower than those before treatment (all P<0.05). The PSQI scores of patients in group C at T4 and T12 were 5.7±1.2 and 4.5±1.2, which were lower than those of patients in groups A and B. (all P<0.05), The SF-36 scores of patients in three groups at T4 and T12 were higher than those before treatment (all P<0.05), and the SF-36 scores of group C at T4 and T12 were 91.7±8.5, 93.1±6.3, which were higher than that of patients in groups A and B (both P<0.05). The incidence of adverse reactions in the three groups were 35.7% (9 cases), 10.7% (3 cases), and 13.8% (4 cases) respectively (P<0.05), the adverse reactions in groups B and C were less than those in group A (P<0.05), and there was no statistical difference between groups B and C (P>0.05).

Lidocaine plaster combined with gabapentin has better analgesic effect in the treatment of HZN, with less incidence of adverse reactions, and can reduce the dosage of systemic drugs, improve patients′ sleep and quality of life, and thus could provide a safe and effective method for the treatment of HZN.

To systematically evaluate the efficacy and safety of different doses of antiviral drugs in the treatment of herpes zoster.

PubMed, EMBASE, Cochrane Library, VIP, CNKI and WanFang database up to April 9, 2022 were searched. Two reviewers selected the studies according to inclusion and exclusion criteria, and the Cochrane bias risk assessment tool was used for quality evaluation. Data were analyzed by Revman 5.4 software for meta-analysis. The qualitative data used relative risk (RR) as the effect index, and the quantitative data used mean difference (MD) as the effect index. The point estimates and 95%CI of each effect were given.

Fourteen randomized controlled trials with 1 831 patients were included in the study. Compared with the 200 mg acyclovir with five times a day, the 800 mg can improve the effective rate, shorten the blister stopping time (MD=-1.29, 95%CI:-1.62- -0.96, P<0.001), relieve the pain faster (MD=-2.73, 95%CI:-4.37- -1.09, P=0.001), shorten the scabbing time (MD=-2.42, 95%CI:-2.96- -1.89, P<0.001) without increasing the adverse reaction rate (RR=1.64, 95%CI:0.80-3.36, P=0.17); Compared with the 300 mg valaciclovir with twice daily, the 900-1 000 mg valaciclovir with three times a day can improve the effective rate(RR=1.17, 95%CI:1.04-1.32, P=0.007), shorten the blister stopping time (MD=-1.53, 95%CI:-2.54- -0.51, P=0.003), relieve the pain faster (MD=-1.04, 95%CI:-1.30- -0.77, P<0.001), shorten the scabbing time (MD=-1.78, 95%CI:-2.80- -0.76, P<0.001), reduce the incidence of postherpetic neuralgia(RR=0.28, 95%CI:0.15-0.52, P<0.001) without increasing the adverse reaction rate (RR=1.47, 95%CI:0.93-2.32, P=0.10); In immunocompromised patients, compared with 1 000 mg valaciclovir with three times a day, 2 000 mg cannot significantly improve the treatment efficacy. There was no significant difference among the efficacy of 250 mg, 500 mg and 750 mg famciclovir, three times a day, in the treatment of herpes zoster.

The 800 mg acyclovir with five times a day; 900-1 000 mg valaciclovir and 250 mg famciclovir with three times a day, are better choices in the treatment of herpes zoster.

To explore the long-term efficacy of low-dose rituximab (RTX) treatment in patients with primary membranous nephropathy (PMN).

Patients with biopsy-proven PMN who received low-dose RTX as initial or second-line regimen from August 2018 to May 2020 in the Department of Nephrology, Tianjin Medical University General Hospital were respectively enrolled. The clinical parameters of patients were urinary protein>3.5 g/24 h, serum albumin<30 g/L and estimated glomerular filtration rate (eGFR)>20 ml·min^-1·(1.73 m²)^-1. The treatment response of patients with PMN was observed during follow-up, and the remission rate of patients with urinary protein<8 g/24 h or ≥8 g/24 h, anti-PLA2R antibody<150 RU/ml or ≥150 RU/ml, eGFR≥ 60 ml·min^-1·(1.73 m²)^-1 or<60 ml·min^-1·(1.73 m²)^-1 were analyzed, respectively.

A total of 40 patients were enrolled, including 26 males and 14 females, aged (53±15) years. There were 14 patients received RTX as initial treatment and 26 patients as second-line therapy. The total median dose of RTX in the first course was 800 (425, 1 075) mg. The overall remission rate at the 1st, 3rd, 6th, 12th and 24th months were 12.5% (5/40), 17.5% (7/40), 47.5% (19/40), 57.5% (23/40), 60% (24/40), respectively. The median overall response time was 6.0 (3.0, 7.5) months. Two cases relapsed. Patients with remission (n=24) had a higher level of baseline eGFR [(93.9±28.0) vs (62.4±28.1) ml·min^-1·(1.73 m²)^-1, P=0.001), and a lower level of both urinary protein [5.9 (5.0, 6.5) vs 11.7 (8.6, 15.5) g/24 h, P<0.001] and anti-PLA2R antibody level [73 (29, 132) vs 453 (182, 950) RU/ml, P=0.004] than those without remission (n=16) 24 month after treatment. There was no statistically significant difference in the remission rate between initial and second-line treatment (P=0.101). Moreover, patients had a higher remission rate in urinary protein<8 g/24 h group (21/26 vs 3/14, P<0.001), anti-PLA2R antibody<150 RU/ml group (16/19 vs 5/16, P=0.002) and eGFR ≥ 60 ml·min^-1·(1.73 m²)^-1 group (22/29 vs 2/11, P=0.003).

Low-dose RTX treatment in PMN is effective during long-term follow-up, and has a lower recurrence rate. The results also suggest that it is more suitable for patients with baseline urinary protein<8 g/24 h, anti-PLA2R antibody<150 RU/ml and eGFR≥ 60 ml·min^-1·(1.73 m²)^-1.

To evaluate the safety and efficacy of a new domestic distal perforated stent graft (Talos stent) in the treatment of Stanford type B aortic dissection (TBAD).

Twenty-five patients with TBAD treated with Talos stent in Yan′an Hospital Affiliated to Kunming Medical University from February 2018 to December 2019 were selected as the research subjects. Intraoperative angiography was performed to determine the number of branch arteries that remained after stent release. On postoperative day 5 (POD5), the pain intensity of the patients was evaluated by visual analog scale (VAS). The computed tomography angiography (CTA) of the patients before operation, 6 months and 12 months after operation were compared including aortic diameter, true lumen diameter, and false lumen diameter at the level of tracheal bifurcation. Follow-up was performed 1 month, 6 months, 12 months, and 24 months after surgery, and the occurrence of stent-related adverse events, reoperation and survival rate were recorded.

The enrolled patients included 19 males and 6 females, aged (52.6±11.1) years. Intraoperative angiography showed that 4 (1, 7) branch arteries were preserved, and the VAS score was 1 (0, 1) on POD5. The aortic diameters at the level of the tracheal bifurcation were (34.9±1.1) mm, (34.6±0.9) mm and (34.8±1.0) mm before surgery, 6 months and 12 months after surgery, and there was no significant difference (P=0.926); the diameters of the main true lumen at the level of the tracheal bifurcation were (13.3±1.6) mm, (21.8±1.0) mm and (22.3±1.1) mm before surgery, 6 months and 12 months postoperatively, while the diameters of the main false lumen at the level of the tracheal bifurcation were (20.8±2.2) mm, (4.5±1.5) mm, and (4.6±1.7) mm, respectively. Compared with before surgery, the diameter of true lumen increased significantly 6 months and 12 months after surgery (both P<0.001), while the diameter of false lumen decreased (both P<0.001). No stent-related adverse events occurred within 30 days after surgery, no secondary operations occurred within 12 months after surgery, no type Ⅰ and type Ⅲ endoleaks, no deaths or cases of paraplegia were reported, and the stent structure and position remained good. There were no deaths or paraplegia cases 24 months postoperatively, and no stent-related adverse events occurred.

Using Talos stent in the treatment of TBAD can effectively help remodel the aorta, while preserve the intercostal artery and spinal artery, with good clinical effect and safety.

In this paper, a patient with prostate cancer and fever developed multiple organ dysfunction during hospitalization, which was clearly caused by hypercalcium crisis. After drug combined with renal replacement therapy, blood calcium decreased and his condition improved. Malignant tumor complicated with hypercalcemia is more common, but prostate cancer complicated with hypercalcic crisis is less common. For patients with malignant tumors, the changes of blood calcium level should be dynamically monitored to avoid missed diagnosis and delayed treatment. Renal replacement therapy should be taken actively on the basis of conservative drug treatment for patients with hypercalcium crisis.

Postherpetic neuralgia (PHN) is an important component of shingles-associated pain (ZAP), and the treatment is mainly anti-neuralgic. Calcium channel modulators gabapentin and pregabalin are first-line drugs, and mirogabalin is the third generation of gabapentin drugs with stronger and longer-lasting analgesic effects. Short-duration spinal cord stimulation (SCS) therapy<3-month PHN has been clinically recognized, and new stimulation modes such as high-frequency SCS and cluster SCS are constantly being used clinically. Female, age, concomitant chronic disease, prodromal pain, area of skin lesions, and degree of pain in acute phase are the key factors in the progression of herpes zoster to PHN. Early analgesia in the acute phase of herpes zoster can prevent PHN, and live attenuated herpes zoster vaccine (ZVL) and recombinant herpes zoster vaccine (RZV) can also be administered. RZV has a higher efficacy rate and longer-lasting utility.

Shingles is a globally prevalent infectious disease. In recent years, with the application of shingles vaccines, preventing the disease through immunization has become a new focus in this field. In addition to the elderly and immunocompromised patients, patients with chronic diseases have a decreased level of varicella-zoster virus-specific immunity, making them a high-risk group for developing shingles. With the further aging of China's population, the number of chronic diseases is still rising rapidly, and the burden of shingles is becoming increasingly heavy. This paper mainly summarizes the incidence of shingles and its complications in patients with diabetes, rheumatoid arthritis, chronic kidney disease, cancer, cardiovascular disease and chronic inflammatory skin disease, and reviews the direct economic burden caused by it, so as to provide ideas for further related research in the future and to formulate prevention and control strategies for shingles in patients with chronic diseases.

Most pituitary adenomas (PA) are benign adenomas that can be cured by surgery, medication and radiation therapy. Only 0.1% ~0.4% of pituitary adenomas have nervous system or systemic metastases and have the characteristics of malignant tumors, which are called pituitary adenocarcinoma (PC). In clinical practice, there are still some refractory PA, showing invasive growth, and the growth rate is fast, insensitive to conventional treatments such as surgery, radiotherapy, and drugs, and the prognosis is extremely poor. Tumor immunotherapy is a promising method for the treatment of malignant tumors. In recent years, more and more studies have been reported on immunotherapy in refractory PA and PC. This article reviews the immune microenvironment of pituitary tumors and the basic and clinical research progress of immunotherapy in refractory PA and PC, in order to provide some reference for the treatment of pituitary tumors.

The novel coronavirus (SARS-CoV-2) continues to mutate during the epidemic, and the virus transmissibility, pathogenicity and immune escape ability also change accordingly, resulting in an increase in reinfection cases. The primary infection of SARS-CoV-2 has a strong preventive effect on the reinfection of alpha, beta and gamma virus strain. At present, the main popular Omicron virus strain has significant immune escape, which can not only antagonize neutralizing antibodies, but also escape the immune protection effect after natural infection, and has a higher threat of reinfection. Prior natural infection with SARS-CoV-2 and/or vaccination are protective factors against severe cases of novel coronavirus pneumonia (COVID-19), but reinfection with SARS-CoV-2 still cumulatively increases the risk of all-cause death, hospitalization, lung and extrapulmonary organ sequelae. Vaccination can control the spread of SARS-CoV-2 to a certain extent, and its effects of preventing severe diseases and reducing hospitalization rates, admission to intensive care units (ICU) rates, and case mortality rates have been recognized globally. However, vaccination failed to significantly improve the cumulative impact of reinfection and reinfection.

Biliary malignant tumor is a kind of malignant tumor with high degree of malignancy, easy recurrence and metastasis, and poor prognosis. In recent years, with the change of people's diet structure and the improvement of living standard, the incidence of biliary malignant tumors is gradually increasing. At the same time, the development and innovation of new immune combination therapies is bringing new hope to patients with biliary tract tumors. In biliary tract tumors, the immunosuppressive microenvironment is composed of various immunosuppressive cells, extracellular matrix, various cytokines, exosomes and immune checkpoint molecules. The complex and heterogeneous immunosuppressive microenvironment of biliary tract tumors hinders the development of immunotherapy. The purpose of this paper is to explore the main factors and related mechanisms affecting the formation of immunosuppressive microenvironment in biliary tract tumors, and summarize the strategies of targeting immunosuppressive microenvironment therapy in biliary tract tumors, aiming to provide ideas for immune clinical therapy of biliary tract tumors.

Varicella-zoster virus infection can cause two different diseases: chickenpox and shingles. Neurological complications, including postherpetic neuralgia and stroke, can occur after the onset of herpes zoster patients. Currently, there are few studies assessing the risk of stroke after the onset of shingles, and the impact of vaccination against shingles on the risk of stroke is unclear. The study aimed to explore the risk of stroke in patients with shingles after onset and to evaluate the impact of shingles vaccination on this risk. A case-control study using national case data from January 2010 to January 2020 from the United States Department of Veterans Affairs database included 2 165 505 patients aged 18 years and older, including 71 911 patients with a history of herpes zoster. The results showed that patients with herpes zoster had an increased risk of stroke within 30 days of onset,ORValues (95%CI) is 1.93 (1.57-2.40),P<0.001； Reduced risk of stroke after vaccination with recombinant shingles vaccine or live shingles vaccine,ORValues (95%CI) were 0.57 (0.46~0.72) and 0.77 (0.65~0.91), bothP<0.001。

Shingles are common in older adults with chronic obstructive pulmonary disease (COPD). Although vaccination is effective in preventing it, shingles vaccination rates are still not up to scale. The Shingles Patient Protection Study (ShiPPS) conducted a self-reported online survey of COPD patients assessing shingles risk awareness, vaccine use and barriers, and the impact of shingles education videos on vaccine intention. The study surveyed U.S. members>50 years of age of the COPD Foundation's Patient Motivation Research Network in fall 2020. Of the 735 survey respondents, 192 (26.1%) reported having previously been infected with shingles, and 49 (25.5%) of them reported increased appearance of COPD symptoms during a shingles episode.